A Safety Study of an Oral EGFR Inhibitor, AV-412, Administered Three Times Weekly in Advanced Solid Tumor Patients

NCT00551850 | Completed Phase 1

• 1 other identifier: AV-412-07-102
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 4

Brief Summary

The Epidermal Growth Factor Receptor (EGFR) is a validated target for the treatment of cancer, and agents targeting EGFR such as erlotinib (Tarceva®) are approved by the FDA for treatment of various solid tumors. AV-412 is a novel inhibitor of the EGFR-tyrosine kinase, with added activity against Her2 and other oncogenic kinases. Based on evidence of preclinical activity in various solid tumors, AV-412 is being developed as a possible novel treatment for cancer in humans. PURPOSE: The purpose of this study is to test the safety and tolerability of AV-412, and determine the maximum tolerated dose of AV-412 when administered orally three times weekly.

Conditions

Advanced Cancer; Refractory Cancer

Keywords

epidermal growth factor inhibitor; solid tumors; advanced cancer

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety, tolerability, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of AV-412 administered orally 3 times weekly and once weekly in subjects with relapsed or refractory solid tumor malignancies.

  4 weeks (1 cycle)

Secondary Outcomes (3)

• Characterize the pharmacokinetic (PK) profile of AV-412

  8 weeks ( 2 cycles)

• Determine the effect of AV-412 on global and targeted gene expression patterns in blood from all subjects enrolled in the MTD expansion cohorts

  8 weeks (2 cycles)

• Evaluate the antineoplastic activity of AV-412

  8 weeks (2 cycles)

Study Arms (1)

1

EXPERIMENTAL

Drug: AV-412

Interventions

AV-412 DRUG

oral solid dosage form administered three times weekly for 4 weeks (1 cycle)

1

Eligibility Criteria

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

You may qualify if:

• Ability to give written informed consent
• years and older
• Evaluable disease or measurable disease according to RECIST.
• Subjects enrolled in the MTD Cohort B must have the following:
• A diagnosis of non-small cell lung carcinoma (NSCLC)
• Received prior therapy with erlotinib or gefitinib for a minimum of 12 weeks
• Demonstrated disease stabilization or an objective response during that prior treatment
• Evidence of disease progression and measurable disease, according to RECIST
• Histologically confirmed solid tumor malignancy that is locally advanced or metastatic
• Disease that is currently refractory to, or not amenable to, standard therapy and/or subjects who are unwilling to try standard chemotherapy
• Disease that is currently not amenable to surgical intervention, due to either medical contraindications or non-resectability of the tumor
• Karnofsky performance status ≥ 70%
• Life expectancy ≥ 3 months, as judged by the investigator
• No childbearing potential; or use of a medically acceptable form of contraception during the study through the end of follow-up period

You may not qualify if:

• Pregnant or lactating women
• Primary CNS malignancy and/or active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy
• Hematologic malignancies (including leukemia of any form, lymphoma, and multiple myeloma)
• Active second malignancy or history of another malignancy within 2 years with the exception of:
• Treated, non-melanoma skin cancers
• Treated carcinoma in situ (CIS) of the breast or cervix
• Controlled, superficial carcinoma of the bladder
• T1a or b prostate carcinoma comprising \< 5% of resected tissue, with prostate specific antigen (PSA) within normal limits (WNL) since resection
• Any of the following hematologic abnormalities:
• Hemoglobin ≤ 9.0 g/dL
• ANC ≤ 1500 per mm3
• Platelet count ≤ 75,000 per mm3
• Any of the following serum chemistry abnormalities:
• Total bilirubin \> 1.5 × the ULN
• AST or ALT ≥ 3 × ULN (≥ 5 × ULN if due to hepatic involvement by tumor)

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (4)

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Kansas Masonic Cancer Research Center

Kansas City, Kansas, 66160, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Montefiore Medical Center

New York, New York, 10461, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

MP 412

Study Officials

• Pankaj Bhargava, M.D.

  AVEO Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 30, 2007
• First Posted: October 31, 2007
• Study Start: October 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: May 1, 2010
• Last Updated: October 4, 2011

Record last verified: 2011-09

Locations

US (4)