Evaluation Of The Efficacy Of The Combination Of Axitinib With Pemetrexed And Cisplatin In The Treatment Of Non-Squamous Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00768755
First received: October 7, 2008
Last updated: March 28, 2013
Last verified: March 2013
  Purpose

AG-013736 (axitinib) in combination with cisplatin and pemetrexed will be evaluated as first-line treatment of patients with locally advanced, recurrent, or metastatic non-squamous, non small cell lung cancer (NSCLC).


Condition Intervention Phase
Carcinoma, Non-Small Cell Lung
Drug: axitinib
Drug: chemotherapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase 2 Study Of Cisplatin/Pemetrexed With Or Without Axitinib (AG-013736) As First-Line Treatment For Patients With Non-Squamous Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Phase 2 baseline until the date of first documented progression or death due to any cause or initiation of subsequent anticancer therapy, assessed every 6 weeks up to 84 weeks ] [ Designated as safety issue: No ]
    Time in months from the date of randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus minus the date of randomization plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]); death was determined from AE data (where the outcome was "Death") or from the end of study data.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline until death or collected bimonthly following discontinuation of study treatment until at least 1 year after randomization of the last participant ] [ Designated as safety issue: No ]
    Time in months from the 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 AE data (where outcome was death) or from follow-up contact data (where the participant current status was death).

  • Percentage of Participants With Objective Response (OR) [ Time Frame: Phase 2 baseline until the date of first documented progression or discontinuation from the study due to any cause or initiation of subsequent anticancer therapy, assessed every 6 weeks up to 84 weeks ] [ Designated as safety issue: No ]
    Percentage of participants with OR based assessment of confirmed complete response (CR)/confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors(RECIST).Confirmed responses: those persist on repeat imaging study at least 4 weeks after initial documentation of response.CR: disappearance of all lesions (target/non target) and no appearance of new lesions.PR: those with at least 30 % decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions,without progression of non target lesions and no appearance of new lesions.

  • Duration of Response (DR) [ Time Frame: Phase 2 baseline until the date of first documented progression or discontinuation from the study due to any cause or initiation of subsequent anticancer therapy, assessed every 6 weeks up to 84 weeks ] [ Designated as safety issue: No ]
    Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause, whichever occurs first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to 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.

  • Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score [ Time Frame: Phase 2 baseline (Cycle1/Day1), Cycle1/Day8, then Day 1 and 8 of each cycle of chemotherapy (C) up to CycleC6, Day 1 of each cycle of single-agent phase (A) up to CycleA8 and end of treatment (EOT) ] [ Designated as safety issue: No ]
    Symptom severity score is comprised of average of 13 MDASI core items (pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting, numbness or tingling) and ranges from 0 to 10. Participants were asked to rate severity of each symptom at their worst in last 24 hours; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Lower scores indicated better outcome.

  • Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score [ Time Frame: Phase 2 baseline (Cycle1/Day1), Cycle1/Day8, then Day 1 and 8 of each cycle of chemotherapy (C) up to CycleC6, Day 1 of each cycle of single-agent phase (A) up to CycleA8 and EOT ] [ Designated as safety issue: No ]
    Symptom interference score is comprised of average of 6 function items from MDASI core (general activity, mood, work, relations with others, walking, and enjoyment of life) and ranges from 0 to 10. Participants were asked to rate how much symptoms have interfered in last 24 hours; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Lower scores indicated better outcome.


Enrollment: 180
Study Start Date: January 2009
Study Completion Date: March 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
Axitinib (continuous) + Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles followed by axitinib maintenance
Drug: axitinib
5mg BID po up to max 10mg BID po
Other Name: AG-013736
Experimental: II
Axitinib (modified) + Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles followed by axitinib maintenance
Drug: axitinib
5mg BID po up to max 10mg BID po paused for 3 days before each cycle of concomitant chemotherapy
Other Name: AG-013736
Active Comparator: III
pemetrexed and cisplatin
Drug: chemotherapy
Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles
Other Name: alimta
Experimental: IV
Axitinib interrupted before each chemo cycle (Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles followed by axitinib maintenance
Drug: axitinib
5mg BID po up to max 10mg BID po paused before each concomitant chemotherapy
Active Comparator: V
pemetrexed and cisplatin
Drug: chemotherapy
Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles
Other Name: alimta

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of adeno-, large cell or bronchioalveolar non-small cell lung cancer
  • Cytologic specimens for diagnosis or for cell type classification must have been obtained from bronchial brushings or washings or from needle aspiration of a defined lesion. Sputum cytology alone will not be acceptable for diagnosis or for cell type classification.
  • Patients with mixed NSCLC with predominantly squamous cell carcinoma should be classified as squamous and thus do not qualify for this study.
  • Stage IIIB with malignant effusion (with cytologic confirmation of malignant pleural or pericardial effusion), Stage IV, or recurrent disease after definitive loco-regional therapy.
  • Candidate for primary treatment with cisplatin and pemetrexed

Exclusion Criteria:

  • Any histological/cytological evidence of predominantly squamous NSCLC.
  • Small cell or carcinoid lung cancer patients are also ineligible.
  • NSCLC that cannot be classified as one of the eligible histologies (adenocarcinoma, large cell or bronchioalveolar).
  • Prior systemic therapy for Stage IIIB (with malignant effusion), Stage IV, or recurrent NSCLC. (Prior treatment with systemic therapy as adjuvant chemotherapy or in conjunction with radiotherapy for Stage II or III NSCLC is permitted if the last dose of chemotherapy was completed 12 months or more prior to randomization).
  • Prior treatment with a VEGF or VEGFR inhibitor.
  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: NCT00768755

  Show 52 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: NCT00768755     History of Changes
Other Study ID Numbers: A4061039
Study First Received: October 7, 2008
Results First Received: March 1, 2012
Last Updated: March 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
non-squamous NSCLC
axitinib
pemetrexed/cisplatin

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Axitinib
Cisplatin
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014