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Axitinib (AG 013736) As Second Line Therapy For Metastatic Renal Cell Cancer

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ClinicalTrials.gov Identifier: NCT00678392
Recruitment Status : Completed
First Posted : May 15, 2008
Results First Posted : March 27, 2012
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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Brief Summary:
The study is designed to demonstrate that axitinib (AG-013736) is superior to sorafenib in delaying tumor progression in patients with metastatic renal cell cancer after failure of one first line regimen.

Condition or disease Intervention/treatment Phase
Kidney Neoplasms Drug: Axitinib (AG-013736) Drug: Sorafenib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 723 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AXITINIB (AG-013736) AS SECOND LINE THERAPY FOR METASTATIC RENAL CELL CANCER: AXIS TRIAL
Actual Study Start Date : September 3, 2008
Actual Primary Completion Date : August 31, 2010
Actual Study Completion Date : February 25, 2016

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Axitinib Drug: Axitinib (AG-013736)
axitinib will be given at a starting dose of 5 mg twice daily [BID] with continuous dosing
Active Comparator: Sorafenib Drug: Sorafenib
sorafenib will be given at a dose of 400 mg twice daily [BID] with continuous dosing


Outcome Measures
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Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    PFS was defined as the time in months from start of study treatment to the first documentation of objective tumor progression of disease (PD) or to death due to any cause, whichever occurs first. PD was assessed by response evaluation criteria in solid tumors (RECIST) version 1.0. PD: >=20 percent (%) increase in the sum of the longest dimensions (LD) of the target lesions taking as a reference the smallest sum of the LD recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. Occurrence of a pleural effusion or ascites was also considered PD if demonstrated by cytological investigation and it was not previously documented. New bone lesions not previously documented were considered PD if confirmed by computed tomography/magnetic resonance imaging or X-ray.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    OS was defined as the duration from start of study treatment to date of death due to any cause. OS was calculated as (months) = (date of death minus the date of first dose of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive.

  2. Objective Response Rate (ORR) [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    ORR = percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0 recorded from first dose of study treatment until PD or death due to any cause. CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks. PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions. PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray.

  3. Duration of Response (DR) [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    DR: time from first documentation of objective tumor response (CR or PR), that was subsequently confirmed, to the first documentation of PD or to death due to any cause, whichever occurred first as per RECIST version 1.0, a) CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks, b) PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions, c) PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray.

  4. Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life- threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.

  5. Percentage of Participants With Adverse Events (AEs) by Severity [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 1= mild; Grade 2= moderate; Grade 3= severe; Grade 4= life-threatening or disabling; Grade 5= death related to AE.

  6. Percentage of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life -threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non -serious AEs.

  7. Number of Participants With Clinically Significant Laboratory Abnormalities: Hematology [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    Hematology laboratory test included hemoglobin, platelet count, white blood cells count, neutrophils and lymphocytes. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

  8. Number of Participants With Clinically Significant Laboratory Abnormalities: Biochemistry [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    Biochemistry laboratory test included parameters: alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bicarbonate, bilirubin, creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia and lipase. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

  9. Number of Participants With Clinically Significant Laboratory Abnormalities: Urinalysis [ Time Frame: From initiation of treatment up to follow-up period (up to 3 years) ]
    Urinalysis included urine blood/ hemoglobin, glucose and protein. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.

  10. Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15) Score [ Time Frame: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698) ]
    FKSI was used to assess quality of life (QoL) for those diagnosed with renal cell cancer and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher scores indicate greater presence of symptoms.

  11. Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Score [ Time Frame: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698) ]
    FKSI-DRS was used to assess quality of life for those diagnosed with renal cell cancer and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptoms) to 36 (very much); higher scores indicate greater presence of symptoms.

  12. Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Health State Profile Utility Score [ Time Frame: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698) ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility or index score. Health state profile component assesses level of health for 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain was rated on a 3-point response scale (1= no problems, 2= some/moderate problems and 3= extreme problems). Scoring formula developed by EuroQol Group assigned a utility value for each domain in the profile. Score were transformed and resulted in a total score range of 0 to 1, with higher scores indicating better health.

  13. Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Visual Analog Scale (VAS) [ Time Frame: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698) ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. VAS component: participants rated their current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed renal cell cancer with a component of clear cell subtype, with metastasis
  • Evidence of measurable disease
  • Must have failed one prior systemic first-line regimen for metastatic renal cell cancer

Exclusion Criteria:

  • Prior treatment for metastatic renal cell cancer with more that one systemic first line therapy
  • Major surgery less than 4 weeks or radiation less than 2 weeks of starting study drug
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00678392


Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00678392    
Other Study ID Numbers: A4061032
AXIS TRIAL
2008-001451-21 ( EudraCT Number )
AXIS ( Other Identifier: Alias Study Number )
First Posted: May 15, 2008    Key Record Dates
Results First Posted: March 27, 2012
Last Update Posted: January 9, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Keywords provided by Pfizer:
Axitinib in Second Line Treatment of Patients With Metastatic Renal Cell Cancer
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Sorafenib
Axitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action