Clinical trial NCT01039948: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2009-12-25
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Phase Ib: Dose Limiting Toxicity and Recommended Phase II Dose
timeFrame: Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereaftert
measure: Phase 2: Objective Response Rate
timeFrame: Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
Secondary outcomes:
measure: Phase 1b: Cmax, Tmax, AUC, t1/2, clearance, and Vd
timeFrame: Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
measure: Phase 2: Progression Free Survival, Overall Survival, Safety
timeFrame: Every 4 weeks for the first 4 months of treatment period, every 8 weeks thereafter
Other outcomes:
Locations:
city: Shatin N.T.
country: Hong Kong
facility: Investigational Site 1
city: Chungcheongbuk-do
country: Korea, Republic of
facility: Investigational Site 2
city: Gyeonggi-do
country: Korea, Republic of
facility: Investigational Site 3
city: Jeollanam-do
country: Korea, Republic of
facility: Investigational Site 4
city: Seoul
country: Korea, Republic of
facility: Investigational Site 5
city: Seoul
country: Korea, Republic of
facility: Investigational Site 6
city: Seoul
country: Korea, Republic of
facility: Investigational Site 7
city: Seoul
country: Korea, Republic of
facility: Investigational Site 8
city: Kuala Lumpur
country: Malaysia
facility: Investigational Site 10
city: Kuala Lumpur
country: Malaysia
facility: Investigational Site 9
city: Pahang
country: Malaysia
facility: Investigational Site 11
city: Manila
country: Philippines
facility: Investigational Site 12
city: Pasig City
country: Philippines
facility: Investigational Site 13
city: Quezon City
country: Philippines
facility: Investigational Site 14
city: Singapore
country: Singapore
facility: Investigational Site 15
city: Changhua
country: Taiwan
facility: Investigational Site 16
city: Chiayi
country: Taiwan
facility: Investigational Site 17
city: Taichung
country: Taiwan
facility: Investigational Site 18
city: Tainan
country: Taiwan
facility: Investigational Site 19
city: Taipei
country: Taiwan
facility: Investigational Site 20
city: Taipei
country: Taiwan
facility: Investigational Site 21
city: Taoyuan
country: Taiwan
facility: Investigational Site 22
city: Bangkok
country: Thailand
facility: Investigational Site 23
city: Chiang Mai
country: Thailand
facility: Investigational Site 24
city: KhonKaen
country: Thailand
facility: Investigational Site 25
city: Songkla
country: Thailand
facility: Investigational Site 26
Study officials:
affiliation: AVEO Pharmaceuticals, Inc.
name: Philip Komarnitsky, MD
role: STUDY_DIRECTOR
References:
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.