Axitinib (AG-013736) For the Treatment of Metastatic Renal Cell Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00920816
First received: June 11, 2009
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Kidney Neoplasms
Drug: Axitinib (AG-013736)
Drug: Sorafenib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Axitinib (AG-013736) For the Treatment of Metastatic Renal Cell Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression Free Survival (PFS): First-Line Participants [ Time Frame: Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107) ] [ Designated as safety issue: No ]
    Time in months from randomization to first documentation of objective tumor progression or death due to any cause. PFS calculated as (first event date minus date of randomization plus 1)/30.4. Tumor progression determined from oncologic assessment data (where it meets criteria for progressive disease [PD]), or from adverse event (AE) data (where outcome was "Death"). Progression using Response Evaluation Criteria in Solid Tumors (RECIST) is >= 20 percent (%) increase in sum of longest diameter of target lesions; measurable increase in non-target lesion; appearance of new lesions.

  • Progression Free Survival (PFS): Second-Line Participants [ Time Frame: Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103) ] [ Designated as safety issue: No ]
    Time in months from randomization to first documentation of objective tumor progression or death due to any cause. PFS calculated as (first event date minus date of randomization plus 1)/30.4. Tumor progression determined from oncologic assessment data (where it meets criteria for progressive disease [PD]), or from adverse event (AE) data (where outcome was "Death"). Progression using Response Evaluation Criteria in Solid Tumors (RECIST) is >= 20 percent (%) increase in sum of longest diameter of target lesions; measurable increase in non-target lesion; appearance of new lesions.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response (OR): First-Line Participants [ Time Frame: Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107) ] [ Designated as safety issue: No ]
    Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.

  • Percentage of Participants With Objective Response (OR): Second-Line Participants [ Time Frame: Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103) ] [ Designated as safety issue: No ]
    Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.

  • Duration of Response (DR): First-Line Participants [ Time Frame: Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107) ] [ Designated as safety issue: No ]
    Time in months from the first documentation of objective tumor response that is subsequently confirmed to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

  • Duration of Response (DR): Second-Line Participants [ Time Frame: Baseline until disease progression or death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103) ] [ Designated as safety issue: No ]
    Time in months from the first documentation of objective tumor response that is subsequently confirmed to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

  • Overall Survival (OS): First-Line Participants [ Time Frame: Baseline until death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 107) ] [ Designated as safety issue: No ]
    Time in months from date of randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

  • Overall Survival (OS): Second-Line Participants [ Time Frame: Baseline until death (assessed on Week 6, Week 12 and thereafter every 8 weeks up to Week 103) ] [ Designated as safety issue: No ]
    Time in months from date of randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).


Other Outcome Measures:
  • Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15): First-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    FKSI-15 questionnaires (lack of energy, side effects, pain, weight loss, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria, sleep) was used to assess quality of life (QoL) for those diagnosed with renal cell cancer. Questions answered on 5-point Likert scale: 0 to 4 (0= not at all, 1= little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score 0 to 60; higher scores=better health states (Individual questions may be reversed coded, as appropriate).

  • Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15): Second-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    FKSI-15 questionnaires (lack of energy, side effects, pain, weight loss, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria, sleep) was used to assess quality of life (QoL) for those diagnosed with renal cell cancer. Questions answered on 5-point Likert scale: 0 to 4 (0= not at all, 1= little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score 0 to 60; higher scores=better health states (Individual questions may be reversed coded, as appropriate).

  • Functional Assessment of Cancer Therapy Kidney Symptom Index -Disease Related Symptoms (FKSI-DRS): First-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    FKSI-DRS: subset of FKSI which is FACT-Kidney Symptom Index questionnaire used to assess QoL for participants diagnosed with renal cell cancer. FKSI contains 15 questions and FKSI-DRS 9 questions (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, hematuria) each ranging from 0 (not at all) to 4 (very much). FKSI-DRS total score 0 to 36; higher scores associated with better health states (Individual questions may be reversed coded, as appropriate).

  • Functional Assessment of Cancer Therapy Kidney Symptom Index -Disease Related Symptoms (FKSI-DRS): Second-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    FKSI-DRS: subset of FKSI which is FACT-Kidney Symptom Index questionnaire used to assess QoL for participants diagnosed with renal cell cancer. FKSI contains 15 questions and FKSI-DRS 9 questions (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, hematuria) each ranging from 0 (not at all) to 4 (very much). FKSI-DRS total score 0 to 36; higher scores associated with better health states (Individual questions may be reversed coded, as appropriate).

  • Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Index Score: First-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

  • Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Index Score: Second-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

  • Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Visual Analog Scale (VAS): First-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C23, end of treatment (up to Week 107), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0: worst imaginable health state to 100: best imaginable health state; higher scores indicate a better health state.

  • Euro Quality of Life Questionnaire- 5 Dimensions (EQ-5D) Visual Analog Scale (VAS): Second-Line Participants [ Time Frame: Baseline (Pre-dose on Cycle [C]1 Day [D]1), D1 of each cycle until C21, end of treatment (up to Week 103), follow-up (28 days after last dose) ] [ Designated as safety issue: No ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0: worst imaginable health state to 100: best imaginable health state; higher scores indicate a better health state.


Enrollment: 492
Study Start Date: August 2009
Estimated Study Completion Date: September 2015
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Axitinib (AG-013736)
axitinib will be given at a starting dose of 5 mg BID with continuous dosing
Active Comparator: B Drug: Sorafenib
sorafenib will be given at a dose of 400 mg BID continuous dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented metastatic renal cell cancer with a component of clear cell histology.
  • Evidence of measurable disease.
  • Patients with mRCC must have received no prior systemic first-line therapy or must have progressive disease per RECIST (version 1.0) after one prior systemic first line regimen for metastatic disease containing sunitinib, cytokine(s), or both.

Exclusion Criteria:

  • Prior treatment for metastatic renal cell cancer with more that one systemic first line therapy.
  • Major surgery less that 4 weeks or radiation less than 2 weeks of starting study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00920816

  Show 119 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00920816     History of Changes
Other Study ID Numbers: A4061051
Study First Received: June 11, 2009
Results First Received: July 26, 2013
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Axitinib in First & Second Line Treatment of Patients With Metastatic Renal Cell Cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sorafenib
Axitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014