PAZOPANIB Efficacy and Tolerance in Desmoids Tumors (DESMOPAZ)

• ClinicalTrials.gov Identifier: NCT01876082
• Recruitment Status: Completed
• First Posted: June 12, 2013
• Results First Posted: March 5, 2021
• Last Update Posted: March 5, 2021
• Sponsor: Institut Bergonié
• Information provided by (Responsible Party): Institut Bergonié

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Progressive Desmoids Tumors
• Interventions: Drug: PAZOPANIB treatment; Drug: Active Comparator: Vinblastine and Methotrexate
• Enrollment: 72

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description	Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Period Title: Overall Study
Started	48	24
Safety Population [1]	48	22 [2]
Completed [3]	46	20
Not Completed	2	4
Reason Not Completed
Withdrawal by Subject	0	2
Protocol Violation	1	0
Adverse Event	1	1
treatment interruption of more than 21 consecutive days observed in cycle 1	0	1
[1] subjects having received at least one administration of treatment allocated by randomization.; [2] 2 patients did not start control treatment; [3] Subjects contributing data to the primary endpoint analysis (6-month non-progression) are considered to have completed the study.

Baseline Characteristics

Arm/Group Title		PAZOPANIB	Vinblastine and Methotrexate	Total
Arm/Group Description		Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.	Total of all reporting groups
Overall Number of Baseline Participants		48	24	72
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	48 participants	24 participants	72 participants
		35.5; (30.6 to 56.0)	42.5; (30.5 to 54.0)	39.8; (30.6 to 54.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	48 participants	24 participants	72 participants
	Female	31 64.6%	15 62.5%	46 63.9%
	Male	17 35.4%	9 37.5%	26 36.1%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
France	Number Analyzed	48 participants	24 participants	72 participants
		48	24	72

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Remaining Alive and Progression-free at 6 Months as Per RECIST 1.1 After the Day of Randomisation (6-month Non-progression Rate).
Description	Percentage of patients remaining alive and progression-free at 6 months as per RECIST 1.1 after the day of randomisation. Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Population evaluable for efficacy included all patients who met eligibility criteria and had received at least one complete cycle or two incomplete cycles of treatment.

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description:	Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Overall Number of Participants Analyzed	46	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	84.8; (71.1 to 93.7)	45.0; (23.1 to 68.5)

2. Secondary Outcome

Title	Percentage of Patients Remaining Alive With Best Overall Response as Per RECIST v1.1.
Description	Best overall response is defined as the best response across all time points (RECIST v1.1). The best overall response is determined once all the data for the participant is known. Each patient has been assigned one of the following categories (RECIST 1.1): complete response (disappearance of all target lesions); partial response (>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); progression (20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and stable disease (nor CR, PR or progression).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Population evaluable for efficacy included all patients who met eligibility criteria and had received at least one complete cycle or two incomplete cycles of treatment.

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description:	Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Overall Number of Participants Analyzed	46	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Complete response	0; (0 to 0)	0; (0 to 0)
Partial response	41.3; (27.0 to 56.8)	30.0; (11.9 to 54.3)
Stable disease	54.4; (39.0 to 69.1)	45.0; (23.1 to 68.5)
Progression	4.4; (0.5 to 14.8)	20.0; (5.7 to 43.7)
Inevaluable for response	0; (0 to 0)	5.0; (0.1 to 24.9)

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) defined as the time from randomization to the first documented progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first. Patients alive and progression free were censored at the date of last follow-up, death, or last patient contact. Progression is assessed as per RECIST v1.1. Progression-free survival is estimated as a function of time using Kaplan-Meier method. 1- and 2-year PFS rates were reported.
Time Frame	Randomization to disease progression, or death due to any cause, whichever occurs first; until 2 years after the last patient randomized.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description:	Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Overall Number of Participants Analyzed	46	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
PFS rate at 1 year	84.8; (70.7 to 92.4)	68.6; (43.0 to 84.5)
PFS rate at 2 years	65.2; (49.6 to 77.0)	68.6; (43.0 to 84.5)

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) defined as the time from randomization to death (due to any cause). Patients alive were censored at the date of last follow-up or last patient contact. Overall survival was estimated as a function of time using Kaplan-Meier method.1- and 2-Year OS rates were reported.
Time Frame	Randomization to disease progression, or death due to any cause, whichever occurs first; until 2 years after the last patient randomized.

Outcome Measure Data

Analysis Population Description

Population evaluable for efficacy included all patients who met eligibility criteria and had received at least one complete cycle or two incomplete cycles of treatment.

Arm/Group Title	PAZOPANIB	Vinblastine and Methotrexate
Arm/Group Description:	Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum	vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
Overall Number of Participants Analyzed	46	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
OS rate at 1 year	100.0 [1]; (NA to NA)	100.0 [1]; (NA to NA)
OS rate at 2 years	97.8; (85.6 to 99.7)	100.0 [2]; (NA to NA)

[1]

Only 1 patient from arm A died after 1 year hence insufficient patient with event to calculate the confidence limits for the 1-year OS rate.

[2]

Only 1 patient from arm A died after 1 year hence insufficient patient with event to calculate the confidence limits for the 2-year OS rate.

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	PAZOPANIB		Vinblastine and Methotrexate
Arm/Group Description	Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum PAZOPANIB treatment: Pazopanib; 800 mg per day; oral administration; at least 1 hour before or 2 hours after a meal,; until disease progression or for 12 months maximum		vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months. Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.
All-Cause Mortality
	PAZOPANIB		Vinblastine and Methotrexate
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/48 (2.08%)		0/22 (0.00%)
Serious Adverse Events
	PAZOPANIB		Vinblastine and Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/48 (41.67%)		10/22 (45.45%)
Blood and lymphatic system disorders
Anemia † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Blood and lymphatic system disorders - Other, specify † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Eye disorders
Retinal detachment † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	1/48 (2.08%)	1	2/22 (9.09%)	2
Diarrhea † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Duodenal stenosis † 1	0/48 (0.00%)	0	1/22 (4.55%)	1
Gastrointestinal pain † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Gastrointestinal disorders - Other, specify † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
General disorders
Fever † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Infusion site extravasation † 1	0/48 (0.00%)	0	1/22 (4.55%)	1
General disorders and administration site conditions - Other, specify † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify † 1	0/48 (0.00%)	0	2/22 (9.09%)	2
Infections and infestations
Sepsis † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Injury, poisoning and procedural complications
Fracture † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/48 (0.00%)	0	2/22 (9.09%)	2
Neutrophil count decreased † 1	2/48 (4.17%)	2	1/22 (4.55%)	1
Metabolism and nutrition disorders
Hypercalcemia † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Musculoskeletal and connective tissue disorders
Myalgia † 1	0/48 (0.00%)	0	1/22 (4.55%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1	1/48 (2.08%)	2	1/22 (4.55%)	1
Nervous system disorders
Paresthesia † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Nervous system disorders - Other, specify † 1	0/48 (0.00%)	0	1/22 (4.55%)	1
Psychiatric disorders
Depression † 1	0/48 (0.00%)	0	1/22 (4.55%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Surgical and medical procedures
Surgical and medical procedures - Other, specify † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Vascular disorders
Hematoma † 1	1/48 (2.08%)	1	0/22 (0.00%)	0
Hypertension † 1	2/48 (4.17%)	2	0/22 (0.00%)	0
Thromboembolic event † 1	1/48 (2.08%)	1	1/22 (4.55%)	1
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	PAZOPANIB		Vinblastine and Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/48 (100.00%)		22/22 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	2/48 (4.17%)	2	5/22 (22.73%)	7
Endocrine disorders
Hypothyroidism † 1	12/48 (25.00%)	13	0/22 (0.00%)	0
Eye disorders - Other, specify † 1	7/48 (14.58%)	8	1/22 (4.55%)	1
Gastrointestinal disorders
Abdominal pain † 1	16/48 (33.33%)	29	6/22 (27.27%)	6
Bloating † 1	4/48 (8.33%)	4	2/22 (9.09%)	2
Constipation † 1	6/48 (12.50%)	6	12/22 (54.55%)	15
Diarrhea † 1	37/48 (77.08%)	60	9/22 (40.91%)	10
Dry mouth † 1	4/48 (8.33%)	4	1/22 (4.55%)	1
Gastroesophageal reflux disease † 1	1/48 (2.08%)	1	2/22 (9.09%)	2
Gastrointestinal disorders - Other, specify † 1	9/48 (18.75%)	12	2/22 (9.09%)	2
Gastrointestinal pain † 1	8/48 (16.67%)	9	1/22 (4.55%)	1
Mucositis oral † 1	13/48 (27.08%)	17	7/22 (31.82%)	11
Nausea † 1	26/48 (54.17%)	34	16/22 (72.73%)	19
Stomach pain † 1	0/48 (0.00%)	0	4/22 (18.18%)	4
Toothache † 1	3/48 (6.25%)	3	1/22 (4.55%)	3
Vomiting † 1	15/48 (31.25%)	24	6/22 (27.27%)	6
General disorders
Edema limbs † 1	3/48 (6.25%)	3	1/22 (4.55%)	2
Fatigue † 1	40/48 (83.33%)	45	15/22 (68.18%)	19
Fever † 1	3/48 (6.25%)	4	2/22 (9.09%)	2
Flu like symptoms † 1	3/48 (6.25%)	3	1/22 (4.55%)	1
Non-cardiac chest pain † 1	2/48 (4.17%)	2	2/22 (9.09%)	2
Pain † 1	4/48 (8.33%)	4	2/22 (9.09%)	2
Infections and infestations
Infections and infestations - Other, specify † 1	8/48 (16.67%)	9	1/22 (4.55%)	1
Tooth infection † 1	4/48 (8.33%)	4	1/22 (4.55%)	1
Urinary tract infection † 1	3/48 (6.25%)	5	0/22 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	15/48 (31.25%)	16	7/22 (31.82%)	8
Aspartate aminotransferase increased † 1	12/48 (25.00%)	12	4/22 (18.18%)	4
Blood bilirubin increased † 1	3/48 (6.25%)	3	2/22 (9.09%)	2
GGT increased † 1	3/48 (6.25%)	8	3/22 (13.64%)	3
Investigations - Other, specify † 1	6/48 (12.50%)	8	0/22 (0.00%)	0
Neutrophil count decreased † 1	4/48 (8.33%)	5	10/22 (45.45%)	14
Platelet count decreased † 1	5/48 (10.42%)	6	0/22 (0.00%)	0
Weight loss † 1	5/48 (10.42%)	6	2/22 (9.09%)	2
Metabolism and nutrition disorders
Anorexia † 1	17/48 (35.42%)	21	5/22 (22.73%)	5
Hypomagnesemia † 1	3/48 (6.25%)	3	0/22 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	13/48 (27.08%)	17	2/22 (9.09%)	2
Back pain † 1	10/48 (20.83%)	11	1/22 (4.55%)	1
Musculoskeletal and connective tissue disorder - Other, specify † 1	6/48 (12.50%)	6	4/22 (18.18%)	7
Myalgia † 1	8/48 (16.67%)	9	5/22 (22.73%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain † 1	6/48 (12.50%)	6	0/22 (0.00%)	0
Nervous system disorders
Dysesthesia † 1	2/48 (4.17%)	2	2/22 (9.09%)	2
Dysgeusia † 1	13/48 (27.08%)	13	1/22 (4.55%)	1
Headache † 1	21/48 (43.75%)	32	4/22 (18.18%)	5
Nervous system disorders - Other, specify † 1	0/48 (0.00%)	0	2/22 (9.09%)	2
Paresthesia † 1	2/48 (4.17%)	2	6/22 (27.27%)	6
Psychiatric disorders
Anxiety † 1	4/48 (8.33%)	4	1/22 (4.55%)	1
Insomnia † 1	5/48 (10.42%)	6	1/22 (4.55%)	1
Psychiatric disorders - Other, specify † 1	4/48 (8.33%)	4	0/22 (0.00%)	0
Reproductive system and breast disorders
Uterine hemorrhage † 1	3/48 (6.25%)	4	0/22 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	4/48 (8.33%)	4	0/22 (0.00%)	0
Epistaxis † 1	4/48 (8.33%)	4	0/22 (0.00%)	0
Respiratory, thoracic and mediastinal disorders - Other, specify † 1	3/48 (6.25%)	3	0/22 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia † 1	6/48 (12.50%)	6	4/22 (18.18%)	4
Dry skin † 1	7/48 (14.58%)	8	0/22 (0.00%)	0
Palmar-plantar erythrodysesthesia syndrome † 1	16/48 (33.33%)	22	0/22 (0.00%)	0
Pruritus † 1	4/48 (8.33%)	4	1/22 (4.55%)	2
Skin and subcutaneous tissue disorders - Other, specify † 1	36/48 (75.00%)	50	3/22 (13.64%)	3
Skin hypopigmentation † 1	10/48 (20.83%)	10	0/22 (0.00%)	0
Vascular disorders
Hot flashes † 1	5/48 (10.42%)	5	0/22 (0.00%)	0
Hypertension † 1	22/48 (45.83%)	27	0/22 (0.00%)	0
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Pr Antoine Italiano, coordinating investigator
• Organization: Department of Medical Oncology, Institut bergonié
• Phone: 05.47.30.60.88
• EMail: a.italiano@bordeaux.unicancer.fr

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

Toulmonde M, Pulido M, Ray-Coquard I, Andre T, Isambert N, Chevreau C, Penel N, Bompas E, Saada E, Bertucci F, Lebbe C, Le Cesne A, Soulie P, Piperno-Neumann S, Sweet S, Cecchi F, Hembrough T, Bellera C, Kind M, Crombe A, Lucchesi C, Le Loarer F, Blay JY, Italiano A. Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol. 2019 Sep;20(9):1263-1272. doi: 10.1016/S1470-2045(19)30276-1. Epub 2019 Jul 19.

• Responsible Party: Institut Bergonié
• ClinicalTrials.gov Identifier: NCT01876082
• Other Study ID Numbers: IB2011-03
• First Submitted: November 6, 2012
• First Posted: June 12, 2013
• Results First Submitted: December 30, 2020
• Results First Posted: March 5, 2021
• Last Update Posted: March 5, 2021