- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01325558
A Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors
July 13, 2016 updated by: Altor BioScience
A Phase I, Open-Label, Multi-center, Competitive Enrollment and Dose-escalation Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors
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.
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Interventional
Enrollment (Anticipated)
30
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University, Winship Cancer Institute
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-
Iowa
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Iowa City, Iowa, United States, 52242
- University of Iowa Hospitals and Clinics
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New York
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Rochester, New York, United States, 14642
- University of Rochester Medical Center, James P. Wilmot Cancer Center
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North Carolina
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Charlotte, North Carolina, United States, 28203
- Carolinas Hematology-Oncology Associates
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed
- Locally advanced or metastatic non-hematologic malignancies
- Measureable
- Refractory to standard therapies or single agent gemcitabine is indicated as a standard treatment option
PRIOR/CONCURRENT THERAPY:
- No concurrent radiotherapy, chemotherapy, immunotherapy or other investigational agents
- Must have recovered from side effects of prior therapies
PATIENT CHARACTERISTICS:
Life expectancy
- > 12 weeks
Performance Status
- ECOG 0 or 1
Bone Marrow Reserve
- Absolute Neutrophil count (AGC/ANC) ≥ 1,500/uL
- Platelets ≥ 100,000/uL
- Hemoglobin > 9 g/dL
Renal Function
- Calculated Glomerular filtration rate (GFR) > 59mL/min/1.73M^2
Hepatic Function
- Total bilirubin ≤ 1.5 X ULN
- AST, ALT, and ALP ≤ 3 X ULN or ≤ 5.0 x ULN, if liver metastasis exists
- PT INR ≤ 1.5 X ULN
Cardiovascular
- No history of clinically significant vascular disease
- No New York Heart Association (NYHA) Class > II heart failure
Hematologic
- No history of bleeding disorders
- No evidence of bleeding diathesis or coagulopathy
- No presence of clinically significant hemoptysis or hematuria, presence of serious non-healing wound or ulceration, or signs of other bleeding
- No evidence of a tumor invasion of any major blood vessel
- No trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within two months of study entry
Surgery/Procedures
- No major surgery or open biopsy within 28 days before drug infusion or evidence of active bleeding postoperatively
- No plan for any major surgery during treatment period
- No presence or requirement of an epidural catheter or lumbar puncture within 48 hours prior to each dose of study treatment
- No anticipation of receiving an epidural catheter or a lumbar puncture within 48 hours after each dose of study treatment
Excluded Medications or Treatment Regimens
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of ALT-836 in combination with gemcitabine
Time Frame: 18 months
|
18 months
|
|
Safety Profile
Time Frame: 18 months
|
Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment
|
18 months
|
Clinical Benefit
Time Frame: 18 months
|
Number of participants with complete response, partial response or stable disease
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18 months
|
Progression Free Survival
Time Frame: 36 months
|
Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month progression-free survival
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36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 36 months
|
Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month overall survival
|
36 months
|
Pharmacokinetics
Time Frame: 18 months
|
Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-836
|
18 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2011
Primary Completion (Actual)
August 1, 2012
Study Completion (Actual)
February 1, 2015
Study Registration Dates
First Submitted
March 9, 2011
First Submitted That Met QC Criteria
March 29, 2011
First Posted (Estimate)
March 30, 2011
Study Record Updates
Last Update Posted (Estimate)
July 15, 2016
Last Update Submitted That Met QC Criteria
July 13, 2016
Last Verified
July 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CA-ALT-836-02-10
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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