A Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors

NCT ID: NCT01325558

Last Updated: 2016-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-02-28

Brief Summary

This is a Phase I, open-label, multi-center, competitive enrollment and dose-escalation study of ALT-836 in combination with standard of care gemcitabine in participants who have locally advanced or metastatic solid tumors. The purpose of this study is to determine the maximum tolerated dose (MTD), and to assess the safety and pharmacokinetic profile of ALT-836 given with gemcitabine. The clinical benefit, progression-free survival and overall survival of study participants will also be assessed.

Detailed Description

Tissue Factor (TF) is over-expressed in most cancer types. Results from many recent studies have suggested a key role for TF in the development of cancer-associated thrombosis, tumor growth, tumor angiogenesis, and tumor metastasis. ALT-836, a recombinant human-chimeric monoclonal antibody, is designed as a direct TF antagonist to block TF displayed by cancers and to inhibit cancer-associated venous thromboembolism, tumor growth, tumor angiogenesis and tumor metastasis. In numerous pre-clinical studies in laboratory animals, including non-human primates, ALT-836 exhibits potent anti-tumor, anti-thrombotic and anti-inflammatory activities with a remarkable safety profile. In humans, ALT-836, administered as a single bolus and monotherapy in patients with coronary artery disease (CAD) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS), is safe and exhibits anti-coagulant and anti-inflammatory effects. A Phase II study using a multi-dose regimen of ALT-836 is being conducted in patients with ALI/ARDS. In the dose-escalation study described in this protocol, the investigators will assess the safety and determine the maximum tolerated dose (MTD) of ALT-836 in combination with gemcitabine in patients with advanced malignancies known to overexpress TF and in which venous thromboembolism is a major complication.

Conditions

Locally Advanced Malignant Neoplasm; Malignant Solid Tumour

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

ALT-836 in combination with gemcitabine

Study participants will receive up to four courses of a 28-day biochemotherapy with the study drug (ALT-836) and gemcitabine. Each treatment course consists of five doses of ALT-836 (on Day 1, 4, 8, 15 and 22) and three doses of gemcitabine (Day 1, 8 and 15). Participants with persistent responses will receive additional two cycles, three doses each, of standard of care gemcitabine therapy.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Exclusion Criteria

• Unfractionated heparin of > 15,000 units/day within 8 hours prior to each dose of study treatment
• Low-molecular weight heparin at a higher dose than recommended for prophylactic used or required within 20 hours prior to each dose of study treatment
• Warfarin used or required within 48 hours prior to each dose of study treatment and the prothrombin time (INR) exceeded the upper limit of normal range
• Direct thrombin inhibitors or Xa inhibitors
• Acetylsalicylic acid used or required within 72 hours prior to each dose of study treatment
• Clopidogrel bisulfate used or required within 48 hours prior to each dose of study treatment
• Anticipated requirement for anti-platelet or anti-coagulant agents excluding non-aspirin NSAID within 48 hours following study treatment infusion

Other

• No active systemic infection requiring parenteral antibiotic therapy
• No history of or presence of a CNS disease
• No history of allergic reactions to compounds of similar chemical or biologic composition
• Not HIV positive
• No women who are pregnant or nursing
• A negative serum pregnancy test if female
• Patients, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
• No history of significant renal, endocrinologic, metabolic, immunologic or hepatic disease
• No evidence of psychiatric illness/social situations
• Other illness that in the opinion of the investigator would exclude the patient from participating
• Must provide informed consent and HIPAA authorization and comply with protocol-specified procedures and follow-up evaluations

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Altor BioScience

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Emory University, Winship Cancer Institute

Atlanta, Georgia, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Rochester Medical Center, James P. Wilmot Cancer Center

Rochester, New York, United States

Carolinas Hematology-Oncology Associates

Charlotte, North Carolina, United States

Countries

United States

Other Identifiers

CA-ALT-836-02-10

Identifier Type: -

Identifier Source: org_study_id