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

NCT01039948 | Completed Phase 1

• 1 other identifier: P06162
• Study Type: interventional
• Target: 203
• Locations: 7 countries
• Sites: 26

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.

Conditions

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

Keywords

Neoplasms; Carcinoma; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histological Type; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Gefitinib; Antineoplastic Agents; Therapeutic Uses; Pharmacologic Actions; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (2)

Phase 2: AV-299 + gefitinib

EXPERIMENTAL

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.

Biological: AV-299 + gefitinib

Phase 2: Gefitinib

ACTIVE COMPARATOR

Phase 2: Gefitinib 250 mg/day, orally.

Drug: Gefitinib

Interventions

AV-299 + gefitinib BIOLOGICAL

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

Also known as: Other name: ficlatuzumab, Formerly SCH 900105

Phase 2: AV-299 + gefitinib

Gefitinib DRUG

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

Also known as: Iressa®

Phase 2: Gefitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (26)

Investigational Site 1

Shatin N.T., Hong Kong

Location

Investigational Site 10

Kuala Lumpur, Malaysia

Location

Investigational Site 9

Kuala Lumpur, Malaysia

Location

Investigational Site 11

Kuala Pahang, Malaysia

Location

Investigational Site 12

Manila, Philippines

Location

Investigational Site 13

Pasig, Philippines

Location

Investigational Site 14

Quezon City, Philippines

Location

Investigational Site 15

Singapore, Singapore

Location

Investigational Site 2

Chungcheongbuk-do, South Korea

Location

Investigational Site 3

Gyeonggi-do, South Korea

Location

Investigational Site 4

Jeollanam-do, South Korea

Location

Investigational Site 5

Seoul, South Korea

Location

Investigational Site 6

Seoul, South Korea

Location

Investigational Site 7

Seoul, South Korea

Location

Investigational Site 8

Seoul, South Korea

Location

Investigational Site 16

Changhua, Taiwan

Location

Investigational Site 17

Chiayi City, Taiwan

Location

Investigational Site 18

Taichung, Taiwan

Location

Investigational Site 19

Tainan, Taiwan

Location

Investigational Site 20

Taipei, Taiwan

Location

Investigational Site 21

Taipei, Taiwan

Location

Investigational Site 22

Taoyuan District, Taiwan

Location

Investigational Site 23

Bangkok, Thailand

Location

Investigational Site 24

Chiang Mai, Thailand

Location

Investigational Site 25

KhonKaen, Thailand

Location

Investigational Site 26

Songkhla, Thailand

Location

Related Publications (1)

• Tan EH, Lim WT, Ahn MJ, Ng QS, Ahn JS, Shao-Weng Tan D, Sun JM, Han M, Payumo FC, McKee K, Yin W, Credi M, Agarwal S, Jac J, Park K. Phase 1b Trial of Ficlatuzumab, a Humanized Hepatocyte Growth Factor Inhibitory Monoclonal Antibody, in Combination With Gefitinib in Asian Patients With NSCLC. Clin Pharmacol Drug Dev. 2018 Jun;7(5):532-542. doi: 10.1002/cpdd.427. Epub 2018 Jan 18.

  PMID: 29346833 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Interventions

ficlatuzumab; Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Philip Komarnitsky, MD

  AVEO Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2009
• First Posted: December 25, 2009
• Study Start: December 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: April 8, 2015

Record last verified: 2015-04

Locations

SG (1); TW (7); MY (3); HK (1); PH (3); TH (4); KR (7)