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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01039948
First received: December 23, 2009
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Carcinoma, Non-Small Cell-Lung
Lung Neoplasms
Lung Cancer
Respiratory Tract Neoplasms
Biological: AV-299 + gefitinib
Drug: Gefitinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by AVEO Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Phase 2: Objective Response Rate [ Time Frame: Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 203
Study Start Date: December 2009
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 2: AV-299 + gefitinib
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
AV-299 is a humanized anti-HGF IgG1 monoclonal antibody directed against free HGF, ligand for c-Met tyrosine kinase receptor.
Other Name: Other name: ficlatuzumab, Formerly SCH 900105
Active Comparator: Phase 2: Gefitinib
Phase 2: Gefitinib 250 mg/day, orally.
Drug: Gefitinib
Gefitinib is a small molecule (drug) which selectively inhibits epidermal growth factor receptor's (EGFR) tyrosine kinase domain.
Other Name: Iressa®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01039948

Locations
Hong Kong
Investigational Site 1
Shatin N.T., Hong Kong
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, Korea, Republic of
Malaysia
Investigational Site 9
Kuala Lumpur, Malaysia
Investigational Site 10
Kuala Lumpur, Malaysia
Investigational Site 11
Pahang, Malaysia
Philippines
Investigational Site 12
Manila, Philippines
Investigational Site 13
Pasig City, Philippines
Investigational Site 14
Quezon City, Philippines
Singapore
Investigational Site 15
Singapore, 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, Taiwan
Thailand
Investigational Site 23
Bangkok, Thailand
Investigational Site 24
Chiang Mai, Thailand
Investigational Site 25
KhonKaen, Thailand
Investigational Site 26
Songkla, Thailand
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
Investigators
Study Director: Philip Komarnitsky, MD AVEO Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01039948     History of Changes
Other Study ID Numbers: P06162
Study First Received: December 23, 2009
Last Updated: March 19, 2013
Health Authority: Singapore: Health Sciences Authority
Malaysia: Ministry of Health
Hong Kong: Department of Health
Philippines: Department of Health
Korea: Food and Drug Administration
Taiwan: Department of Health
Thailand: Food and Drug Administration

Keywords provided by AVEO Pharmaceuticals, Inc.:
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

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Gefitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014