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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Carcinoma, Non-Small Cell Lung

Intervention / Treatment
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* Drug: axitinib
* Drug: axitinib
* Drug: chemotherapy
* Drug: axitinib
* Drug: chemotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I<br>Axitinib (continuous) + Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles followed by axitinib maintenance | Drug: axitinib<br>* 5mg BID po up to max 10mg BID po<br>* Other names: AG-013736;|
| Experimental: II<br>Axitinib (modified) + Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles followed by axitinib maintenance | Drug: axitinib<br>* 5mg BID po up to max 10mg BID po paused for 3 days before each cycle of concomitant chemotherapy<br>* Other names: AG-013736;|
| Active Comparator: III<br>pemetrexed and cisplatin | Drug: chemotherapy<br>* Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles<br>* Other names: alimta;|
| Experimental: IV<br>Axitinib interrupted before each chemo cycle (Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles followed by axitinib maintenance | Drug: axitinib<br>* 5mg BID po up to max 10mg BID po paused before each concomitant chemotherapy<br>|
| Active Comparator: V<br>pemetrexed and cisplatin | Drug: chemotherapy<br>* Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles<br>* Other names: alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | 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). | Baseline until death or collected bimonthly following discontinuation of study treatment until at least 1 year after randomization of the last participant | 
| Percentage of Participants With Objective Response (OR) | 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. | 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 | 
| Duration of Response (DR) | 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. | 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 | 
| Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Severity Score | 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. | 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) | 
| Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Symptom Interference Score | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-squamous NSCLC, axitinib, pemetrexed/cisplatin