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

Carcinoma, Non-Small Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00768755
• Other study ID #: A4061039
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 7, 2008
• Last updated: October 6, 2015
• Start date: January 2009
• Est. completion date: March 2012

Study information

• Verified date: October 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: March 2012
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small Cell Lung
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• axitinib
5mg BID po up to max 10mg BID po
• axitinib
5mg BID po up to max 10mg BID po paused for 3 days before each cycle of concomitant chemotherapy
• chemotherapy
Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles
• axitinib
5mg BID po up to max 10mg BID po paused before each concomitant chemotherapy
• chemotherapy
Pemetrexed(500mg/m2)/Cisplatin(75mg/m2) x max 6 cycles

Locations

Country	Name	City	State
Italy	Pfizer Investigational Site	Genova
Italy	Pfizer Investigational Site	Lido di Camaiore (LU)
Italy	Pfizer Investigational Site	Orbassano (TO)
Japan	Pfizer Investigational Site	Sunto-gun	Shizuoka
Poland	Pfizer Investigational Site	Lubin
Poland	Pfizer Investigational Site	Otwock
Poland	Pfizer Investigational Site	Pila
Poland	Pfizer Investigational Site	Poznan
Poland	Pfizer Investigational Site	Poznan
Poland	Pfizer Investigational Site	Prabuty
Poland	Pfizer Investigational Site	Warszawa
Romania	Pfizer Investigational Site	Bacau
Romania	Pfizer Investigational Site	Iasi
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Pyatigorsk
Russian Federation	Pfizer Investigational Site	Saint-Petersburg
Russian Federation	Pfizer Investigational Site	St.Petersburg
Spain	Pfizer Investigational Site	Castellon
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Palma de Mallorca
Spain	Pfizer Investigational Site	Sevilla
Spain	Pfizer Investigational Site	Terrassa	Barcelona
Switzerland	Pfizer Investigational Site	Basel
Switzerland	Pfizer Investigational Site	Basel
Switzerland	Pfizer Investigational Site	Bruderholz
Switzerland	Pfizer Investigational Site	Liestal
Taiwan	Pfizer Investigational Site	Taichung
Taiwan	Pfizer Investigational Site	Taichung
Taiwan	Pfizer Investigational Site	Taipei
Taiwan	Pfizer Investigational Site	Taipei
Ukraine	Pfizer Investigational Site	Dnipropetrovsk
Ukraine	Pfizer Investigational Site	Kyiv
United Kingdom	Pfizer Investigational Site	Bournemouth
United Kingdom	Pfizer Investigational Site	Brighton
United Kingdom	Pfizer Investigational Site	Dundee
United Kingdom	Pfizer Investigational Site	Middlesex
United Kingdom	Pfizer Investigational Site	Northwood	Middlesex
United Kingdom	Pfizer Investigational Site	Poole
United Kingdom	Pfizer Investigational Site	Romford	Essex
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Bloomington	Illinois
United States	Pfizer Investigational Site	Decatur	Georgia
United States	Pfizer Investigational Site	East Providence	Rhode Island
United States	Pfizer Investigational Site	East Providence	Rhode Island
United States	Pfizer Investigational Site	Hershey	Pennsylvania
United States	Pfizer Investigational Site	Huntsville	Alabama
United States	Pfizer Investigational Site	Macon	Georgia
United States	Pfizer Investigational Site	Marietta	Georgia
United States	Pfizer Investigational Site	Peoria	Illinois
United States	Pfizer Investigational Site	Sandy Springs	Georgia
United States	Pfizer Investigational Site	West Reading	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Italy,  Japan,  Poland,  Romania,  Russian Federation,  Spain,  Switzerland,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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	No

External Links

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