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

Lung Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01039948
• Other study ID #: P06162
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 23, 2009
• Last updated: April 6, 2015
• Start date: December 2009
• Est. completion date: August 2013

Study information

• Verified date: April 2015
• Source: AVEO Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences AuthorityMalaysia: Ministry of HealthHong Kong: Department of HealthPhilippines: Department of HealthKorea: Food and Drug AdministrationTaiwan: Department of HealthThailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small Cell-Lung
• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Neoplasms
• Respiratory Tract Neoplasms

Intervention

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

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

Locations

Country	Name	City	State
Hong Kong	Investigational Site 1	Shatin N.T.
Korea, Republic of	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
Malaysia	Investigational Site 10	Kuala Lumpur
Malaysia	Investigational Site 9	Kuala Lumpur
Malaysia	Investigational Site 11	Pahang
Philippines	Investigational Site 12	Manila
Philippines	Investigational Site 13	Pasig City
Philippines	Investigational Site 14	Quezon City
Singapore	Investigational Site 15	Singapore
Taiwan	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
Thailand	Investigational Site 23	Bangkok
Thailand	Investigational Site 24	Chiang Mai
Thailand	Investigational Site 25	KhonKaen
Thailand	Investigational Site 26	Songkla

Sponsors (1)

Lead Sponsor	Collaborator
AVEO Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Hong Kong,  Korea, Republic of,  Malaysia,  Philippines,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Phase 2: Objective Response Rate		Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter	Yes
Secondary	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	Yes
Secondary	Phase 2: Progression Free Survival, Overall Survival, Safety		Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter	Yes