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

Phase 1

Completed

• Conditions: Locally Advanced Malignant Neoplasm; Malignant Solid Tumour

• Registration Number: NCT01325558
• Lead Sponsor: Altor BioScience

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.

Study Timeline

• Study First Submitted: 2011-03-09
• Study First Submitted QC: 2011-03-29
• Study First Posted: 2011-03-30
• Study Start: 2011-05
• Primary Completion: 2012-08
• Study Completion: 2015-02
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-13
• Last Update Posted: 2016-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Safety Profile	18 months	Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment
Maximum Tolerated Dose (MTD) of ALT-836 in combination with gemcitabine	18 months
Clinical Benefit	18 months	Number of participants with complete response, partial response or stable disease
Progression Free Survival	36 months	Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month progression-free survival

Secondary Outcome Measures

Name	Time	Method
Overall Survival	36 months	Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month overall survival
Pharmacokinetics	18 months	Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-836

Trial Locations

Locations (4)

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

Emory University, Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Carolinas Hematology-Oncology Associates; 🇺🇸 Charlotte, North Carolina, United States

University of Rochester Medical Center, James P. Wilmot Cancer Center; 🇺🇸 Rochester, New York, United States