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

Primary Purpose

Carcinoma, Non-Small Cell-Lung, Lung Neoplasms, Lung Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AV-299 + gefitinib
Gefitinib
Sponsored by
AVEO Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small Cell-Lung focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site 1
  • Investigational Site 2
  • Investigational Site 3
  • Investigational Site 4
  • Investigational Site 5
  • Investigational Site 6
  • Investigational Site 7
  • Investigational Site 8
  • Investigational Site 10
  • Investigational Site 9
  • Investigational Site 11
  • Investigational Site 12
  • Investigational Site 13
  • Investigational Site 14
  • Investigational Site 15
  • Investigational Site 16
  • Investigational Site 17
  • Investigational Site 18
  • Investigational Site 19
  • Investigational Site 20
  • Investigational Site 21
  • Investigational Site 22
  • Investigational Site 23
  • Investigational Site 24
  • Investigational Site 25
  • Investigational Site 26

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Phase 2: AV-299 + gefitinib

Phase 2: Gefitinib

Arm 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.

Phase 2: Gefitinib 250 mg/day, orally.

Outcomes

Primary Outcome Measures

Phase Ib: Dose Limiting Toxicity and Recommended Phase II Dose
Phase 2: Objective Response Rate

Secondary Outcome Measures

Phase 1b: Cmax, Tmax, AUC, t1/2, clearance, and Vd
Phase 2: Progression Free Survival, Overall Survival, Safety

Full Information

First Posted
December 23, 2009
Last Updated
April 6, 2015
Sponsor
AVEO Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01039948
Brief Title
A Phase 1b/2 Study in Asian Subjects With Non-Small Cell Lung Cancer
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AVEO Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
203 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 2: AV-299 + gefitinib
Arm Type
Experimental
Arm 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.
Arm Title
Phase 2: Gefitinib
Arm Type
Active Comparator
Arm Description
Phase 2: Gefitinib 250 mg/day, orally.
Intervention Type
Biological
Intervention Name(s)
AV-299 + gefitinib
Other Intervention Name(s)
Other name: ficlatuzumab, Formerly SCH 900105
Intervention Description
AV-299 is a humanized anti-HGF IgG1 monoclonal antibody directed against free HGF, ligand for c-Met tyrosine kinase receptor.
Intervention Type
Drug
Intervention Name(s)
Gefitinib
Other Intervention Name(s)
Iressa®
Intervention Description
Gefitinib is a small molecule (drug) which selectively inhibits epidermal growth factor receptor's (EGFR) tyrosine kinase domain.
Primary Outcome Measure Information:
Title
Phase Ib: Dose Limiting Toxicity and Recommended Phase II Dose
Time Frame
Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereaftert
Title
Phase 2: Objective Response Rate
Time Frame
Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
Secondary Outcome Measure Information:
Title
Phase 1b: Cmax, Tmax, AUC, t1/2, clearance, and Vd
Time Frame
Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
Title
Phase 2: Progression Free Survival, Overall Survival, Safety
Time Frame
Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philip Komarnitsky, MD
Organizational Affiliation
AVEO Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site 1
City
Shatin N.T.
Country
Hong Kong
Facility Name
Investigational Site 2
City
Chungcheongbuk-do
Country
Korea, Republic of
Facility Name
Investigational Site 3
City
Gyeonggi-do
Country
Korea, Republic of
Facility Name
Investigational Site 4
City
Jeollanam-do
Country
Korea, Republic of
Facility Name
Investigational Site 5
City
Seoul
Country
Korea, Republic of
Facility Name
Investigational Site 6
City
Seoul
Country
Korea, Republic of
Facility Name
Investigational Site 7
City
Seoul
Country
Korea, Republic of
Facility Name
Investigational Site 8
City
Seoul
Country
Korea, Republic of
Facility Name
Investigational Site 10
City
Kuala Lumpur
Country
Malaysia
Facility Name
Investigational Site 9
City
Kuala Lumpur
Country
Malaysia
Facility Name
Investigational Site 11
City
Pahang
Country
Malaysia
Facility Name
Investigational Site 12
City
Manila
Country
Philippines
Facility Name
Investigational Site 13
City
Pasig City
Country
Philippines
Facility Name
Investigational Site 14
City
Quezon City
Country
Philippines
Facility Name
Investigational Site 15
City
Singapore
Country
Singapore
Facility Name
Investigational Site 16
City
Changhua
Country
Taiwan
Facility Name
Investigational Site 17
City
Chiayi
Country
Taiwan
Facility Name
Investigational Site 18
City
Taichung
Country
Taiwan
Facility Name
Investigational Site 19
City
Tainan
Country
Taiwan
Facility Name
Investigational Site 20
City
Taipei
Country
Taiwan
Facility Name
Investigational Site 21
City
Taipei
Country
Taiwan
Facility Name
Investigational Site 22
City
Taoyuan
Country
Taiwan
Facility Name
Investigational Site 23
City
Bangkok
Country
Thailand
Facility Name
Investigational Site 24
City
Chiang Mai
Country
Thailand
Facility Name
Investigational Site 25
City
KhonKaen
Country
Thailand
Facility Name
Investigational Site 26
City
Songkla
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
29346833
Citation
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.
Results Reference
derived

Learn more about this trial

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

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