Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed

• ClinicalTrials.gov Identifier: NCT02761057
• Recruitment Status: Active, not recruiting
• First Posted: May 4, 2016
• Results First Posted: September 2, 2022
• Last Update Posted: May 16, 2024
• Sponsor: National Cancer Institute (NCI)
• Collaborator: Canadian Cancer Trials Group
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Locally Advanced Papillary Renal Cell Carcinoma; Metastatic Papillary Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Unresectable Renal Cell Carcinoma
• Interventions: Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Drug: Crizotinib; Drug: Savolitinib; Drug: Sunitinib Malate
• Enrollment: 152

Participant Flow

Recruitment Details	152 participants were enrolled and randomly assigned. Five participants were excluded because of inadequate baseline disease assessment or no evidence of metastatic disease. Therefore, 147 were deemed eligible and analyzable for the primary analysis.
Pre-assignment Details

Arm/Group Title	Arm I (Sunitinib Malate)	Arm II (Cabozantinib S-malate)	Arm III (Crizotinib Closed to Accrual 12/5/18)	Arm IV (Savolitinib Closed to Accrual 12/5/18)
Arm/Group Description	Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO	Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO	Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Crizotinib: Given PO	Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Savolitinib: Given PO
Period Title: Overall Study
Started	48	46	28	30
Eligible	46	44	28	29
Received Protocol Treatment	45	43	27	28
Completed	0	0	0	0
Not Completed	48	46	28	30
Reason Not Completed
Ineligible - No Measurable Disease	1	1	0	1
Ineligible - Inadequate Baseline Disease Assessment	1	1	0	0
Currently On Study Treatment	0	3	0	0
Adverse Event	11	9	5	3
Refusal Unrelated to Adverse Event	2	2	0	2
Progression/Relapse	29	27	20	23
Death	2	2	1	1
Other - Not Protocol Specified	2	1	2	0

Baseline Characteristics

Arm/Group Title		Arm I (Sunitinib Malate)	Arm II (Cabozantinib S-malate)	Arm III (Crizotinib Closed to Accrual 12/5/18)	Arm IV (Savolitinib Closed to Accrual 12/5/18)	Total
Arm/Group Description		Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Sunitinib Malate: Given PO	Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO	Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Crizotinib: Given PO	Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Savolitinib: Given PO	Total of all reporting groups
Overall Number of Baseline Participants		46	44	28	29	147
Baseline Analysis Population Description		Analysis population included only eligible participants.
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
		65; (58 to 73)	65; (58 to 75)	68; (61 to 75)	67; (58 to 72)	66; (58 to 75)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
	Female	11 23.9%	8 18.2%	6 21.4%	10 34.5%	35 23.8%
	Male	35 76.1%	36 81.8%	22 78.6%	19 65.5%	112 76.2%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
	Hispanic or Latino	0 0.0%	2 4.5%	1 3.6%	2 6.9%	5 3.4%
	Not Hispanic or Latino	46 100.0%	40 90.9%	26 92.9%	24 82.8%	136 92.5%
	Unknown or Not Reported	0 0.0%	2 4.5%	1 3.6%	3 10.3%	6 4.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	1 3.4%	1 0.7%
	Asian	1 2.2%	1 2.3%	1 3.6%	0 0.0%	3 2.0%
	Native Hawaiian or Other Pacific Islander	1 2.2%	0 0.0%	0 0.0%	0 0.0%	1 0.7%
	Black or African American	5 10.9%	9 20.5%	4 14.3%	3 10.3%	21 14.3%
	White	39 84.8%	32 72.7%	22 78.6%	21 72.4%	114 77.6%
	More than one race	0 0.0%	0 0.0%	0 0.0%	1 3.4%	1 0.7%
	Unknown or Not Reported	0 0.0%	2 4.5%	1 3.6%	3 10.3%	6 4.1%
Previous Systemic Therapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
		3 6.5%	2 4.5%	2 7.1%	3 10.3%	10 6.8%
Histological Subtype (Local Assessment) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
	Type 1	8 17.4%	9 20.5%	5 17.9%	5 17.2%	27 18.4%
	Type 2	24 52.2%	25 56.8%	15 53.6%	15 51.7%	79 53.7%
	Not otherwise specified	14 30.4%	10 22.7%	8 28.6%	9 31.0%	41 27.9%
		[1] Measure Description: Papillary renal cell carcinoma (pRCC) histological subtype as determined by a local pathologist. Type 1 is characterized by small cells in a a single layer with scant basophilic cytoplasm and oval nuclei. Type 2 is characterized by large cells with eosinophilic cytoplasm and spherical nuclei with prominent nucleoli and pseudostratification. Type 1 is more common and grows slowly and type 2 is more aggressive and grows more quickly. In general, type 2 pRCC has a poorer prognosis than type 1.
Histological Subtype (Central Assessment) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
	Type 1	12 26.1%	14 31.8%	9 32.1%	6 20.7%	41 27.9%
	Type 2	21 45.7%	16 36.4%	13 46.4%	13 44.8%	63 42.9%
	Mixed or Other	11 23.9%	12 27.3%	5 17.9%	7 24.1%	35 23.8%
	Missing	2 4.3%	2 4.5%	1 3.6%	3 10.3%	8 5.4%
		[1] Measure Description: Papillary renal cell carcinoma (pRCC) histological subtype as determined by a central pathologic assessment. Type 1 is characterized by small cells in a a single layer with scant basophilic cytoplasm and oval nuclei. Type 2 is characterized by large cells with eosinophilic cytoplasm and spherical nuclei with prominent nucleoli and pseudostratification. Type 1 is more common and grows slowly and type 2 is more aggressive and grows more quickly. In general, type 2 pRCC has a poorer prognosis than type 1.
IMDC Risk Group [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
	Favourable	14 30.4%	10 22.7%	8 28.6%	6 20.7%	38 25.9%
	Intermediate	26 56.5%	28 63.6%	16 57.1%	19 65.5%	89 60.5%
	High	6 13.0%	6 13.6%	4 14.3%	4 13.8%	20 13.6%
		[1] Measure Description: The International Metastatic Renal Cell Carcinoma Database Consortium's (IMDC) prognostic model to predict survival of metastatic kidney cancer patients has become the standard model used in clinical trials to categorize patients into favorable, intermediate, and poor risk based on treatment time, performance status, and hemoglobin, calcium, neutrophil, and platelet counts.
Zubrod Performance Score [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
	0	29 63.0%	29 65.9%	18 64.3%	15 51.7%	91 61.9%
	1	17 37.0%	15 34.1%	10 35.7%	14 48.3%	56 38.1%
		[1] Measure Description: Zubrod performance status scores range from 0 to 4, with higher scores reflecting greater disability. This study only includes participants with a score of 0-1. 0: Fully active, able to carry on all pre-disease performance without restriction. 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
Previous Nephrectomy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
		34 73.9%	32 72.7%	26 92.9%	21 72.4%	113 76.9%
Metastatic Sites of Interest; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	46 participants	44 participants	28 participants	29 participants	147 participants
Bone		7 15.2%	6 13.6%	5 17.9%	8 27.6%	26 17.7%
CNS		0 0.0%	0 0.0%	1 3.6%	0 0.0%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target lesions over smallest sum observed, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause; assessed up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis population included eligible participants.

Arm/Group Title	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
Arm/Group Description:	Experimental: Arm I (sunitinib malate) Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity Drug: Sunitinib Malate Given PO Other Names: SU011248 SU11248 sunitinib Sunitinib Malate Sutent	Experimental: Arm II (cabozantinib s-malate) Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Cabozantinib S-malate Given PO Other Names: BMS-907351 Cabometyx CABOZANTINIB S-MALATE Cometriq XL-184 XL184	Experimental: Arm III (crizotinib closed to accrual 12/5/18) Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Crizotinib Given PO Other Names: CRIZOTINIB MET Tyrosine Kinase Inhibitor PF-02341066XXPF-02341066 PF-2341066 Xalkori	Experimental: Arm IV (savolitinib closed to accrual 12/5/18) Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Savolitinib Given PO Other Names: AZD 6094 AZD6094 HMPL-504 SAVOLITINIB Volitinib
Overall Number of Participants Analyzed	46	44	28	29
Median (95% Confidence Interval); Unit of Measure: months
	5.6; (2.9 to 6.7)	9.0; (5.6 to 12.4)	2.8; (2.6 to 3.6)	3.0; (2.8 to 7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Cabozantinib
	Comments	A proportional hazards model was used to compare the Hazard Ratio (HR) for PFS.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.019
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.97
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Response Rate (RR)
Description	The response rate (RR) is defined as the combined rate of confirmed and unconfirmed partial response and confirmed and unconfirmed complete response. Complete response (CR) is defined as the complete disappearance of all target and non-target lesions, along with no new lesions. Partial response (PR) is defined as >=30% decrease of the sum of appropriate diameters of all target measurable lesions, along with no new lesions.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis population included eligible participants.

Arm/Group Title	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
Arm/Group Description:	Experimental: Arm I (sunitinib malate) Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity Drug: Sunitinib Malate Given PO Other Names: SU011248 SU11248 sunitinib Sunitinib Malate Sutent	Experimental: Arm II (cabozantinib s-malate) Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Cabozantinib S-malate Given PO Other Names: BMS-907351 Cabometyx CABOZANTINIB S-MALATE Cometriq XL-184 XL184	Experimental: Arm III (crizotinib closed to accrual 12/5/18) Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Crizotinib Given PO Other Names: CRIZOTINIB MET Tyrosine Kinase Inhibitor PF-02341066XXPF-02341066 PF-2341066 Xalkori	Experimental: Arm IV (savolitinib closed to accrual 12/5/18) Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Savolitinib Given PO Other Names: AZD 6094 AZD6094 HMPL-504 SAVOLITINIB Volitinib
Overall Number of Participants Analyzed	46	44	28	29
Measure Type: Number; Unit of Measure: percentage of participants
	4.35	22.73	0	3.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Cabozantinib
	Comments	The Chi-Square test will be used to compare RR between sunitinib and cabozantinib.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.10
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Duration from date of randomization to date of death from any cause.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Analysis population included eligible participants.

Arm/Group Title	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
Arm/Group Description:	Experimental: Arm I (sunitinib malate) Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity Drug: Sunitinib Malate Given PO Other Names: SU011248 SU11248 sunitinib Sunitinib Malate Sutent	Experimental: Arm II (cabozantinib s-malate) Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Cabozantinib S-malate Given PO Other Names: BMS-907351 Cabometyx CABOZANTINIB S-MALATE Cometriq XL-184 XL184	Experimental: Arm III (crizotinib closed to accrual 12/5/18) Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Crizotinib Given PO Other Names: CRIZOTINIB MET Tyrosine Kinase Inhibitor PF-02341066XXPF-02341066 PF-2341066 Xalkori	Experimental: Arm IV (savolitinib closed to accrual 12/5/18) Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Savolitinib Given PO Other Names: AZD 6094 AZD6094 HMPL-504 SAVOLITINIB Volitinib
Overall Number of Participants Analyzed	46	44	28	29
Median (95% Confidence Interval); Unit of Measure: months
	16.4; (12.8 to 21.6)	20.0 [1]; (11.3 to NA)	19.9 [1]; (11.2 to NA)	11.7; (6.7 to 28.9)

[1]

There was not enough data to estimate the upper bound 95% CI

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib, Cabozantinib
	Comments	The log-rank test will be used to compare OS.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.51
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Duration of treatment and follow up until death or 3 years post registration

Outcome Measure Data

Analysis Population Description

Eligible participants who received at least one dose of protocol treatment.

Arm/Group Title	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
Arm/Group Description:	Experimental: Arm I (sunitinib malate) Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity Drug: Sunitinib Malate Given PO Other Names: SU011248 SU11248 sunitinib Sunitinib Malate Sutent	Experimental: Arm II (cabozantinib s-malate) Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Cabozantinib S-malate Given PO Other Names: BMS-907351 Cabometyx CABOZANTINIB S-MALATE Cometriq XL-184 XL184	Experimental: Arm III (crizotinib closed to accrual 12/5/18) Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Crizotinib Given PO Other Names: CRIZOTINIB MET Tyrosine Kinase Inhibitor PF-02341066XXPF-02341066 PF-2341066 Xalkori	Experimental: Arm IV (savolitinib closed to accrual 12/5/18) Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Savolitinib Given PO Other Names: AZD 6094 AZD6094 HMPL-504 SAVOLITINIB Volitinib
Overall Number of Participants Analyzed	45	43	27	28
Measure Type: Number; Unit of Measure: Participants
Abdominal pain	1	3	0	0
Acute kidney injury	1	0	0	0
Alanine aminotransferase increased	1	1	2	0
Allergic reaction	0	0	1	0
Anemia	6	0	1	0
Anorexia	0	1	0	0
Aspartate aminotransferase increased	1	0	1	0
Back pain	0	1	0	0
Confusion	0	1	0	0
Dehydration	1	0	0	1
Diarrhea	3	2	0	0
Duodenal ulcer	1	0	0	0
Dyspnea	0	0	0	1
Edema limbs	0	0	1	2
Epistaxis	1	0	0	0
Facial pain	1	0	0	0
Fall	0	2	0	0
Fatigue	3	6	2	0
Febrile neutropenia	0	1	0	0
Gastrointestinal disorders - Other, specify	0	1	0	0
Generalized muscle weakness	1	0	0	1
Genital edema	0	0	0	1
Hearing impaired	0	0	0	1
Hematoma	0	1	0	1
Hypercalcemia	0	1	0	0
Hyperkalemia	0	0	1	0
Hypermagnesemia	0	1	0	0
Hypertension	9	14	0	1
Hypoalbuminemia	1	0	1	0
Hypocalcemia	0	1	0	0
Hypomagnesemia	0	2	0	0
Hyponatremia	2	3	0	3
Hypophosphatemia	0	6	0	0
Hypoxia	0	1	0	0
Infections and infestations - Other, specify	0	1	0	0
Lung infection	0	1	0	0
Lymphedema	0	0	0	1
Lymphocyte count decreased	2	0	0	0
Lymphocyte count increased	1	0	0	0
Mucositis oral	0	1	0	0
Muscle weakness lower limb	0	1	0	0
Nausea	4	0	0	0
Nervous system disorders - Other, specify	0	1	0	0
Neutrophil count decreased	4	0	0	0
Pain	1	0	0	0
Pain in extremity	0	1	1	0
Palmar-plantar erythrodysesthesia syndrome	0	9	0	0
Pancreatitis	0	1	0	0
Paronychia	0	1	0	0
Platelet count decreased	2	0	0	0
Pleural effusion	1	0	0	0
Pneumonitis	0	1	0	0
Proteinuria	1	1	0	0
Rash maculo-papular	0	0	1	1
Renal calculi	1	0	0	0
Reproductive system and breast disorders - Other	0	1	0	0
Sinus bradycardia	0	0	1	0
Sinus tachycardia	0	0	1	0
Skin ulceration	0	1	0	0
Somnolence	1	0	0	0
Syncope	0	0	1	0
Thromboembolic event	0	6	0	2
Thrombotic thrombocytopenic purpura	1	0	0	0
Vascular disorders - Other, specify	0	0	0	1
Vomiting	1	0	0	0
White blood cell decreased	5	0	0	0

5. Other Pre-specified Outcome

Title	MET Mutation Rate
Description	The hazard ratio between the MET inhibitor versus (vs.) sunitinib in those with versus without the mutation (i.e., the interaction) will be compared. Response Evaluation Criteria in Solid Tumors (RECIST) response rate (confirmed and unconfirmed partial response and complete response) based on MET mutation/expression level will be compared using the chi-square test.
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Duration of treatment and follow up until death or 3 years post registration
Adverse Event Reporting Description	143 participants who received protocol treatment were evaluable for AEs: 45 on sunitinib arm, 43 on cabozantinib arm, 27 on crizotinib arm, and 28 on savolitinib arm. Adverse Events (AEs) are reported by CTCAE Version 4.0 and Serious Adverse Events (SAEs) are reported by CTCAE Version 5.0. All started participants were monitored/assessed for All-Cause Mortality".
Arm/Group Title	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
Arm/Group Description	Experimental: Arm I (sunitinib malate) Patients receive sunitinib malate PO on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Sunitinib Malate Given PO Other Names: SU011248 SU11248 sunitinib Sunitinib Malate Sutent	Experimental: Arm II (cabozantinib s-malate) Patients receive cabozantinib s-malate PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Cabozantinib S-malate Given PO Other Names: BMS-907351 Cabometyx CABOZANTINIB S-MALATE Cometriq XL-184 XL184	Experimental: Arm III (crizotinib closed to accrual 12/5/18) Patients receive crizotinib PO BID on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Crizotinib Given PO Other Names: CRIZOTINIB MET Tyrosine Kinase Inhibitor PF-02341066 PF-02341066 PF-2341066 Xalkori	Experimental: Arm IV (savolitinib closed to accrual 12/5/18) Patients receive savolitinib PO on days 1-42. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Drug: Savolitinib Given PO Other Names: AZD 6094 AZD6094 HMPL-504 SAVOLITINIB Volitinib
All-Cause Mortality
	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	24/46 (52.17%)	22/44 (50.00%)	16/28 (57.14%)	21/29 (72.41%)
Serious Adverse Events
	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	15/45 (33.33%)	19/43 (44.19%)	8/27 (29.63%)	11/28 (39.29%)
Blood and lymphatic system disorders
Anemia †	1/45 (2.22%)	1/43 (2.33%)	2/27 (7.41%)	0/28 (0.00%)
Blood and lymphatic system disorders - Other †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Cardiac disorders
Sinus tachycardia †	1/45 (2.22%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Endocrine disorders
Hypothyroidism †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Gastrointestinal disorders
Abdominal distension †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Abdominal pain †	1/45 (2.22%)	2/43 (4.65%)	0/27 (0.00%)	1/28 (3.57%)
Ascites †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Constipation †	1/45 (2.22%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Diarrhea †	1/45 (2.22%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Gastrointestinal disorders-Other †	0/45 (0.00%)	2/43 (4.65%)	0/27 (0.00%)	0/28 (0.00%)
Hemorrhoids †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Nausea †	2/45 (4.44%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Pancreatitis †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Small intestinal obstruction †	1/45 (2.22%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Vomiting †	2/45 (4.44%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
General disorders
Death NOS †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Edema face †	0/45 (0.00%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Edema limbs †	1/45 (2.22%)	0/43 (0.00%)	2/27 (7.41%)	1/28 (3.57%)
Fatigue †	1/45 (2.22%)	1/43 (2.33%)	1/27 (3.70%)	1/28 (3.57%)
Fever †	0/45 (0.00%)	0/43 (0.00%)	0/27 (0.00%)	1/28 (3.57%)
Non-cardiac chest pain †	0/45 (0.00%)	0/43 (0.00%)	1/27 (3.70%)	2/28 (7.14%)
Pain †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Sudden death NOS †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Immune system disorders
Allergic reaction †	0/45 (0.00%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Infections and infestations
Device related infection †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Infections and infestations-Other †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Lung infection †	0/45 (0.00%)	2/43 (4.65%)	0/27 (0.00%)	0/28 (0.00%)
Skin infection †	0/45 (0.00%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Urinary tract infection †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	2/28 (7.14%)
Injury, poisoning and procedural complications
Fall †	0/45 (0.00%)	2/43 (4.65%)	0/27 (0.00%)	0/28 (0.00%)
Investigations
Creatinine increased †	2/45 (4.44%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
INR increased †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Lymphocyte count decreased †	2/45 (4.44%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Neutrophil count decreased †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Platelet count decreased †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Metabolism and nutrition disorders
Acidosis †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Dehydration †	1/45 (2.22%)	0/43 (0.00%)	1/27 (3.70%)	1/28 (3.57%)
Hyperkalemia †	1/45 (2.22%)	2/43 (4.65%)	0/27 (0.00%)	0/28 (0.00%)
Hyperuricemia †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Hypoalbuminemia †	2/45 (4.44%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Hypocalcemia †	1/45 (2.22%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Hypomagnesemia †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Hyponatremia †	3/45 (6.67%)	2/43 (4.65%)	0/27 (0.00%)	1/28 (3.57%)
Musculoskeletal and connective tissue disorders
Arthralgia †	0/45 (0.00%)	0/43 (0.00%)	0/27 (0.00%)	1/28 (3.57%)
Back pain †	0/45 (0.00%)	2/43 (4.65%)	0/27 (0.00%)	0/28 (0.00%)
Flank pain †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Generalized muscle weakness †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	1/28 (3.57%)
Muscle weakness lower limb †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Pain in extremity †	0/45 (0.00%)	1/43 (2.33%)	1/27 (3.70%)	0/28 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other †	1/45 (2.22%)	3/43 (6.98%)	2/27 (7.41%)	1/28 (3.57%)
Tumor pain †	0/45 (0.00%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Nervous system disorders
Dizziness †	0/45 (0.00%)	0/43 (0.00%)	2/27 (7.41%)	0/28 (0.00%)
Nervous system disorders-Other †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Paresthesia †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Presyncope †	1/45 (2.22%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Stroke †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Syncope †	0/45 (0.00%)	0/43 (0.00%)	2/27 (7.41%)	0/28 (0.00%)
Psychiatric disorders
Anxiety †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Confusion †	2/45 (4.44%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Delirium †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Renal and urinary disorders
Acute kidney injury †	4/45 (8.89%)	0/43 (0.00%)	0/27 (0.00%)	1/28 (3.57%)
Chronic kidney disease †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Hematuria †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Proteinuria †	2/45 (4.44%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Urine discoloration †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	0/28 (0.00%)
Reproductive system and breast disorders
Genital edema †	0/45 (0.00%)	0/43 (0.00%)	0/27 (0.00%)	1/28 (3.57%)
Respiratory, thoracic and mediastinal disorders
Dyspnea †	2/45 (4.44%)	2/43 (4.65%)	1/27 (3.70%)	2/28 (7.14%)
Pleural effusion †	3/45 (6.67%)	1/43 (2.33%)	0/27 (0.00%)	1/28 (3.57%)
Pneumonitis †	0/45 (0.00%)	2/43 (4.65%)	0/27 (0.00%)	0/28 (0.00%)
Respiratory failure †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Vascular disorders
Hematoma †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Hypertension †	0/45 (0.00%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Hypotension †	2/45 (4.44%)	0/43 (0.00%)	1/27 (3.70%)	0/28 (0.00%)
Thromboembolic event †	1/45 (2.22%)	5/43 (11.63%)	0/27 (0.00%)	1/28 (3.57%)
Vascular disorders-Other †	0/45 (0.00%)	0/43 (0.00%)	0/27 (0.00%)	1/28 (3.57%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sunitinib	Cabozantinib	Crizotinib	Savolitinib
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	44/45 (97.78%)	41/43 (95.35%)	26/27 (96.30%)	27/28 (96.43%)
Blood and lymphatic system disorders
Anemia †	17/45 (37.78%)	12/43 (27.91%)	7/27 (25.93%)	7/28 (25.00%)
Blood and lymphatic system disorders - Other †	2/45 (4.44%)	5/43 (11.63%)	0/27 (0.00%)	1/28 (3.57%)
Cardiac disorders
Sinus bradycardia †	2/45 (4.44%)	1/43 (2.33%)	3/27 (11.11%)	2/28 (7.14%)
Sinus tachycardia †	3/45 (6.67%)	1/43 (2.33%)	0/27 (0.00%)	2/28 (7.14%)
Ear and labyrinth disorders
Ear and labyrinth disorders-Other †	0/45 (0.00%)	1/43 (2.33%)	1/27 (3.70%)	2/28 (7.14%)
Hearing impaired †	0/45 (0.00%)	0/43 (0.00%)	1/27 (3.70%)	2/28 (7.14%)
Endocrine disorders
Hyperthyroidism †	3/45 (6.67%)	6/43 (13.95%)	0/27 (0.00%)	0/28 (0.00%)
Hypothyroidism †	8/45 (17.78%)	17/43 (39.53%)	0/27 (0.00%)	0/28 (0.00%)
Eye disorders
Blurred vision †	2/45 (4.44%)	3/43 (6.98%)	1/27 (3.70%)	0/28 (0.00%)
Eye disorders-Other †	0/45 (0.00%)	3/43 (6.98%)	6/27 (22.22%)	0/28 (0.00%)
Flashing lights †	0/45 (0.00%)	0/43 (0.00%)	2/27 (7.41%)	0/28 (0.00%)
Gastrointestinal disorders
Abdominal pain †	8/45 (17.78%)	8/43 (18.60%)	3/27 (11.11%)	7/28 (25.00%)
Bloating †	2/45 (4.44%)	2/43 (4.65%)	0/27 (0.00%)	2/28 (7.14%)
Constipation †	13/45 (28.89%)	15/43 (34.88%)	8/27 (29.63%)	4/28 (14.29%)
Diarrhea †	22/45 (48.89%)	25/43 (58.14%)	11/27 (40.74%)	6/28 (21.43%)
Dry mouth †	5/45 (11.11%)	8/43 (18.60%)	1/27 (3.70%)	0/28 (0.00%)
Dyspepsia †	6/45 (13.33%)	4/43 (9.30%)	2/27 (7.41%)	1/28 (3.57%)
Esophagitis †	0/45 (0.00%)	0/43 (0.00%)	2/27 (7.41%)	0/28 (0.00%)
Flatulence †	2/45 (4.44%)	3/43 (6.98%)	0/27 (0.00%)	2/28 (7.14%)
Gastroesophageal reflux disease †	3/45 (6.67%)	5/43 (11.63%)	1/27 (3.70%)	1/28 (3.57%)
Gastrointestinal disorders-Other †	3/45 (6.67%)	7/43 (16.28%)	0/27 (0.00%)	0/28 (0.00%)
Mucositis oral †	13/45 (28.89%)	16/43 (37.21%)	1/27 (3.70%)	0/28 (0.00%)
Nausea †	20/45 (44.44%)	18/43 (41.86%)	8/27 (29.63%)	15/28 (53.57%)
Vomiting †	10/45 (22.22%)	10/43 (23.26%)	3/27 (11.11%)	6/28 (21.43%)
General disorders
Chills †	3/45 (6.67%)	1/43 (2.33%)	0/27 (0.00%)	3/28 (10.71%)
Edema limbs †	7/45 (15.56%)	6/43 (13.95%)	9/27 (33.33%)	12/28 (42.86%)
Fatigue †	30/45 (66.67%)	31/43 (72.09%)	16/27 (59.26%)	16/28 (57.14%)
Fever †	2/45 (4.44%)	5/43 (11.63%)	2/27 (7.41%)	2/28 (7.14%)
General disorders and admin site conditions - Other †	2/45 (4.44%)	3/43 (6.98%)	1/27 (3.70%)	1/28 (3.57%)
Non-cardiac chest pain †	6/45 (13.33%)	3/43 (6.98%)	1/27 (3.70%)	1/28 (3.57%)
Pain †	5/45 (11.11%)	8/43 (18.60%)	4/27 (14.81%)	3/28 (10.71%)
Infections and infestations
Lung infection †	2/45 (4.44%)	4/43 (9.30%)	0/27 (0.00%)	0/28 (0.00%)
Upper respiratory infection †	1/45 (2.22%)	3/43 (6.98%)	0/27 (0.00%)	0/28 (0.00%)
Urinary tract infection †	6/45 (13.33%)	3/43 (6.98%)	0/27 (0.00%)	2/28 (7.14%)
Injury, poisoning and procedural complications
Bruising †	4/45 (8.89%)	1/43 (2.33%)	0/27 (0.00%)	0/28 (0.00%)
Fall †	3/45 (6.67%)	2/43 (4.65%)	1/27 (3.70%)	0/28 (0.00%)
Fracture †	1/45 (2.22%)	0/43 (0.00%)	0/27 (0.00%)	2/28 (7.14%)
Investigations
Alanine aminotransferase increased †	7/45 (15.56%)	14/43 (32.56%)	8/27 (29.63%)	4/28 (14.29%)
Alkaline phosphatase increased †	6/45 (13.33%)	6/43 (13.95%)	4/27 (14.81%)	10/28 (35.71%)
Aspartate aminotransferase increased †	9/45 (20.00%)	17/43 (39.53%)	7/27 (25.93%)	4/28 (14.29%)
Blood bilirubin increased †	3/45 (6.67%)	2/43 (4.65%)	0/27 (0.00%)	3/28 (10.71%)
Creatinine increased †	16/45 (35.56%)	8/43 (18.60%)	10/27 (37.04%)	10/28 (35.71%)
Investigations-Other †	4/45 (8.89%)	6/43 (13.95%)	1/27 (3.70%)	1/28 (3.57%)
Lymphocyte count decreased †	12/45 (26.67%)	6/43 (13.95%)	3/27 (11.11%)	5/28 (17.86%)
Neutrophil count decreased †	10/45 (22.22%)	7/43 (16.28%)	1/27 (3.70%)	0/28 (0.00%)
Platelet count decreased †	19/45 (42.22%)	9/43 (20.93%)	0/27 (0.00%)	1/28 (3.57%)
Weight gain †	0/45 (0.00%)	0/43 (0.00%)	0/27 (0.00%)	2/28 (7.14%)
Weight loss †	10/45 (22.22%)	13/43 (30.23%)	2/27 (7.41%)	4/28 (14.29%)
White blood cell decreased †	15/45 (33.33%)	9/43 (20.93%)	0/27 (0.00%)	1/28 (3.57%)
Metabolism and nutrition disorders
Anorexia †	18/45 (40.00%)	22/43 (51.16%)	5/27 (18.52%)	7/28 (25.00%)
Dehydration †	7/45 (15.56%)	3/43 (6.98%)	0/27 (0.00%)	1/28 (3.57%)
Hypercalcemia †	1/45 (2.22%)	4/43 (9.30%)	0/27 (0.00%)	0/28 (0.00%)
Hyperglycemia †	6/45 (13.33%)	11/43 (25.58%)	6/27 (22.22%)	5/28 (17.86%)
Hyperkalemia †	5/45 (11.11%)	7/43 (16.28%)	4/27 (14.81%)	3/28 (10.71%)
Hypernatremia †	1/45 (2.22%)	3/43 (6.98%)	0/27 (0.00%)	2/28 (7.14%)
Hypoalbuminemia †	9/45 (20.00%)	11/43 (25.58%)	6/27 (22.22%)	13/28 (46.43%)
Hypocalcemia †	2/45 (4.44%)	14/43 (32.56%)	5/27 (18.52%)	8/28 (28.57%)
Hypoglycemia †	1/45 (2.22%)	2/43 (4.65%)	0/27 (0.00%)	2/28 (7.14%)
Hypokalemia †	2/45 (4.44%)	7/43 (16.28%)	1/27 (3.70%)	1/28 (3.57%)
Hypomagnesemia †	0/45 (0.00%)	8/43 (18.60%)	0/27 (0.00%)	0/28 (0.00%)
Hyponatremia †	7/45 (15.56%)	6/43 (13.95%)	1/27 (3.70%)	8/28 (28.57%)
Hypophosphatemia †	4/45 (8.89%)	14/43 (32.56%)	1/27 (3.70%)	0/28 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia †	2/45 (4.44%)	5/43 (11.63%)	0/27 (0.00%)	2/28 (7.14%)
Back pain †	3/45 (6.67%)	8/43 (18.60%)	2/27 (7.41%)	4/28 (14.29%)
Bone pain †	0/45 (0.00%)	3/43 (6.98%)	1/27 (3.70%)	1/28 (3.57%)
Flank pain †	2/45 (4.44%)	4/43 (9.30%)	0/27 (0.00%)	1/28 (3.57%)
Musculoskeletal and connective tiss disorder - Other †	1/45 (2.22%)	1/43 (2.33%)	2/27 (7.41%)	1/28 (3.57%)
Myalgia †	1/45 (2.22%)	4/43 (9.30%)	0/27 (0.00%)	1/28 (3.57%)
Pain in extremity †	4/45 (8.89%)	8/43 (18.60%)	2/27 (7.41%)	3/28 (10.71%)
Nervous system disorders
Dizziness †	7/45 (15.56%)	3/43 (6.98%)	2/27 (7.41%)	5/28 (17.86%)
Dysgeusia †	15/45 (33.33%)	19/43 (44.19%)	9/27 (33.33%)	2/28 (7.14%)
Headache †	7/45 (15.56%)	11/43 (25.58%)	1/27 (3.70%)	4/28 (14.29%)
Nervous system disorders-Other †	1/45 (2.22%)	3/43 (6.98%)	1/27 (3.70%)	1/28 (3.57%)
Peripheral sensory neuropathy †	0/45 (0.00%)	7/43 (16.28%)	3/27 (11.11%)	1/28 (3.57%)
Tremor †	1/45 (2.22%)	0/43 (0.00%)	2/27 (7.41%)	0/28 (0.00%)
Psychiatric disorders
Anxiety †	5/45 (11.11%)	4/43 (9.30%)	1/27 (3.70%)	0/28 (0.00%)
Depression †	6/45 (13.33%)	4/43 (9.30%)	0/27 (0.00%)	1/28 (3.57%)
Insomnia †	5/45 (11.11%)	5/43 (11.63%)	0/27 (0.00%)	1/28 (3.57%)
Renal and urinary disorders
Hematuria †	10/45 (22.22%)	8/43 (18.60%)	0/27 (0.00%)	1/28 (3.57%)
Proteinuria †	7/45 (15.56%)	10/43 (23.26%)	0/27 (0.00%)	2/28 (7.14%)
Renal and urinary disorders-Other †	2/45 (4.44%)	5/43 (11.63%)	0/27 (0.00%)	1/28 (3.57%)
Respiratory, thoracic and mediastinal disorders
Cough †	9/45 (20.00%)	5/43 (11.63%)	4/27 (14.81%)	4/28 (14.29%)
Dyspnea †	8/45 (17.78%)	13/43 (30.23%)	5/27 (18.52%)	6/28 (21.43%)
Epistaxis †	4/45 (8.89%)	4/43 (9.30%)	0/27 (0.00%)	0/28 (0.00%)
Hoarseness †	2/45 (4.44%)	7/43 (16.28%)	0/27 (0.00%)	0/28 (0.00%)
Sore throat †	4/45 (8.89%)	3/43 (6.98%)	1/27 (3.70%)	0/28 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia †	3/45 (6.67%)	2/43 (4.65%)	0/27 (0.00%)	0/28 (0.00%)
Dry skin †	4/45 (8.89%)	3/43 (6.98%)	0/27 (0.00%)	1/28 (3.57%)
Palmar-plantar erythrodysesthesia syndrome †	11/45 (24.44%)	21/43 (48.84%)	0/27 (0.00%)	0/28 (0.00%)
Pruritus †	3/45 (6.67%)	4/43 (9.30%)	0/27 (0.00%)	2/28 (7.14%)
Rash acneiform †	2/45 (4.44%)	5/43 (11.63%)	3/27 (11.11%)	0/28 (0.00%)
Rash maculo-papular †	5/45 (11.11%)	9/43 (20.93%)	2/27 (7.41%)	4/28 (14.29%)
Skin and subcutaneous tissue disorders - Other †	9/45 (20.00%)	5/43 (11.63%)	2/27 (7.41%)	0/28 (0.00%)
Vascular disorders
Hot flashes †	0/45 (0.00%)	0/43 (0.00%)	0/27 (0.00%)	2/28 (7.14%)
Hypertension †	21/45 (46.67%)	29/43 (67.44%)	4/27 (14.81%)	9/28 (32.14%)
Hypotension †	1/45 (2.22%)	3/43 (6.98%)	2/27 (7.41%)	0/28 (0.00%)
Thromboembolic event †	0/45 (0.00%)	4/43 (9.30%)	0/27 (0.00%)	2/28 (7.14%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Genitourinary Committee Statistician
• Organization: SWOG Statistics and Data Management Center
• Phone: 2066674623
• EMail: mplets@fredhutch.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pal SK, Tangen C, Thompson IM Jr, Balzer-Haas N, George DJ, Heng DYC, Shuch B, Stein M, Tretiakova M, Humphrey P, Adeniran A, Narayan V, Bjarnason GA, Vaishampayan U, Alva A, Zhang T, Cole S, Plets M, Wright J, Lara PN Jr. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 20;397(10275):695-703. doi: 10.1016/S0140-6736(21)00152-5. Epub 2021 Feb 13.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02761057
• Other Study ID Numbers: NCI-2015-01707; NCI-2015-01707 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S1500 ( Other Identifier: SWOG ); S1500 ( Other Identifier: CTEP ); U10CA180888 ( U.S. NIH Grant/Contract )
• First Submitted: May 2, 2016
• First Posted: May 4, 2016
• Results First Submitted: June 6, 2022
• Results First Posted: September 2, 2022
• Last Update Posted: May 16, 2024