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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Altor Bioscience Corporation
ClinicalTrials.gov Identifier:
NCT01325558
First received: March 9, 2011
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Locally Advanced Malignant Neoplasm
Malignant Solid Tumour
Biological: ALT-836 in combination with gemcitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Altor Bioscience Corporation:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of ALT-836 in combination with gemcitabine [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Safety Profile [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment

  • Clinical Benefit [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Number of participants with complete response, partial response or stable disease

  • Progression Free Survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month progression-free survival


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month overall survival

  • Pharmacokinetics [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-836


Estimated Enrollment: 30
Study Start Date: May 2011
Estimated Study Completion Date: March 2014
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01325558

Locations
United States, Georgia
Emory University, Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, New York
University of Rochester Medical Center, James P. Wilmot Cancer Center
Rochester, New York, United States, 14642
United States, North Carolina
Carolinas Hematology-Oncology Associates
Charlotte, North Carolina, United States, 28203
Sponsors and Collaborators
Altor Bioscience Corporation
  More Information

No publications provided

Responsible Party: Altor Bioscience Corporation
ClinicalTrials.gov Identifier: NCT01325558     History of Changes
Other Study ID Numbers: CA-ALT-836-02-10
Study First Received: March 9, 2011
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Altor Bioscience Corporation:
cancer
tissue factor
solid tumor
ovarian cancer
breast cancer
non-small cell lung cancer
colon cancer
pancreatic cancer
head and neck cancer
prostate cancer
soft-tissue sarcoma
metastatic
gemcitabine
anti-tumor
venous thromboembolism

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014