A Phase 1b/2 Study in Asian Subjects With Non-Small Cell Lung Cancer

A Phase 1b/2 Study of AV-299 (Formerly SCH 900105) in Combination With Gefitinib in Asian Subjects With Non-Small Cell Lung Cancer (P06162)

Sponsors

Lead Sponsor: AVEO Pharmaceuticals, Inc.

Source AVEO Pharmaceuticals, Inc.
Brief Summary

During Phase 1b portion, there will be a dose-escalation of AV-299 (formerly SCH 900105) in combination with the recommended dose of gefitinib in subjects with NSCLC or advanced solid tumor. The objective is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended Phase 2 dose (RP2D) in combination with gefitinib for the Phase 2 portion. The Phase 2 is an open-label, 2-arm, randomized study designed to compare the combination of AV-299 (formerly SCH900105) and gefitinib versus gefitinib alone in clinically selected Asian subjects with previously untreated lung adenocarcinoma who have a high likelihood of harboring activating EGFR mutations. Subjects who progress after initial disease control in the gefitinib alone arm may crossover to the combination arm.

Overall Status Completed
Start Date 2009-12-01
Completion Date 2013-08-01
Primary Completion Date 2013-08-01
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Phase Ib: Dose Limiting Toxicity and Recommended Phase II Dose Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereaftert
Phase 2: Objective Response Rate Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
Secondary Outcome
Measure Time Frame
Phase 1b: Cmax, Tmax, AUC, t1/2, clearance, and Vd Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
Phase 2: Progression Free Survival, Overall Survival, Safety Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
Enrollment 203
Condition
Intervention

Intervention Type: Biological

Intervention Name: AV-299 + gefitinib

Description: AV-299 is a humanized anti-HGF IgG1 monoclonal antibody directed against free HGF, ligand for c-Met tyrosine kinase receptor.

Arm Group Label: Phase 2: AV-299 + gefitinib

Other Name: Other name: ficlatuzumab, Formerly SCH 900105

Intervention Type: Drug

Intervention Name: Gefitinib

Description: Gefitinib is a small molecule (drug) which selectively inhibits epidermal growth factor receptor's (EGFR) tyrosine kinase domain.

Arm Group Label: Phase 2: Gefitinib

Other Name: Iressa®

Eligibility

Criteria:

Inclusion Criteria: - Asian ethnicity. - ECOG performance status of 0-2. - Phase 1b (only): Diagnosis of one of the following unresectable NSCLC with or without prior therapy advanced solid tumor that progressed after standard therapy - Phase 2 only: Histologic or cytologic confirmation of unresectable locally advanced or metastatic stage IIIB/IV lung adenocarcinoma with at least one measurable lesion, per Response Evaluation Criteria in Solid Tumors (RECIST-Version 1.1). - Phase 2 only: Never smoker or light ex-smoker. - Available tumor tissue for determination of EGFR mutational status and immunohistochemistry analysis - Adequate hematologic, hepatic, renal and coagulation function - No active central nervous system metastases - Prior radiotherapy is allowed if 14 days from first dose of study drug and toxicity is resolved; additionally in Phase 2 only, ≥1 target lesion not irradiated or with definitive progression after prior radiation therapy. - Agreement to use effective contraception. - Phase 2 only: Subjects on Gefitinib monotherapy arm must have documented CR, PR, or SD for ≥12 weeks prior to disease progression in order to cross over to combination therapy arm. Exclusion Criteria: - Phase 2 only: Prior chemotherapy or prior treatment with epidermal growth factor receptor (EGFR) inhibitor, including both tyrosine kinase inhibitors and monoclonal antibodies. There is no limit to the number of therapies for subject being considered for Phase 1b. - History of neoplasm other than the entry diagnosis. - Pregnancy or lactation. - Myocardial infarction within 6 months prior to initiation of study treatment. - A serious active infection. - Known human immunodeficiency virus infection. - A serious underlying medical condition that would impair the ability of the subject to receive protocol treatment. - A major surgical procedure, open biopsy, or significant traumatic injury. - Thrombotic or embolic events. - Known or suspected allergy/hypersensitivity to any agent given in the course of this trial. - Any condition that impairs absorption of oral agents or the subject's ability to swallow whole pills. - Diarrhea ≥ Grade 2 or active Inflammatory Bowel Disease. - Severe acute or chronic medical, psychiatric, or behavioral condition or laboratory abnormality. - Diagnosis of interstitial lung disease. - Any medications or treatments prohibited by the protocol.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Philip Komarnitsky, MD Study Director AVEO Pharmaceuticals, Inc.
Location
Facility:
Investigational Site 1 | Shatin N.T., Hong Kong
Investigational Site 2 | Chungcheongbuk-do, Korea, Republic of
Investigational Site 3 | Gyeonggi-do, Korea, Republic of
Investigational Site 4 | Jeollanam-do, Korea, Republic of
Investigational Site 5 | Seoul, Korea, Republic of
Investigational Site 6 | Seoul, Korea, Republic of
Investigational Site 7 | Seoul, Korea, Republic of
Investigational Site 8 | Seoul, Korea, Republic of
Investigational Site 10 | Kuala Lumpur, Malaysia
Investigational Site 9 | Kuala Lumpur, Malaysia
Investigational Site 11 | Pahang, Malaysia
Investigational Site 12 | Manila, Philippines
Investigational Site 13 | Pasig City, Philippines
Investigational Site 14 | Quezon City, Philippines
Investigational Site 15 | Singapore, Singapore
Investigational Site 16 | Changhua, Taiwan
Investigational Site 17 | Chiayi, Taiwan
Investigational Site 18 | Taichung, Taiwan
Investigational Site 19 | Tainan, Taiwan
Investigational Site 20 | Taipei, Taiwan
Investigational Site 21 | Taipei, Taiwan
Investigational Site 22 | Taoyuan, Taiwan
Investigational Site 23 | Bangkok, Thailand
Investigational Site 24 | Chiang Mai, Thailand
Investigational Site 25 | KhonKaen, Thailand
Investigational Site 26 | Songkla, Thailand
Location Countries

Hong Kong

Korea, Republic of

Malaysia

Philippines

Singapore

Taiwan

Thailand

Verification Date

2015-04-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Phase 2: AV-299 + gefitinib

Type: Experimental

Description: Phase 2: AV-299 (formerly SCH 900105) administered IV at RP2D (as determined by Phase 1b portion) in combination with gefitinib 250 mg/day orally.

Label: Phase 2: Gefitinib

Type: Active Comparator

Description: Phase 2: Gefitinib 250 mg/day, orally.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News