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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

Phase 1
18 Years
Open (Enrolling)
Locally Advanced Malignant Neoplasm, Malignant Solid Tumour

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Trial Information

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

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

Inclusion Criteria


- 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


- No concurrent radiotherapy, chemotherapy, immunotherapy or other investigational

- Must have recovered from side effects of prior therapies


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


- No history of clinically significant vascular disease

- No New York Heart Association (NYHA) Class > II heart failure


- 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


- 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

- Clopidogrel bisulfate used or required within 48 hours prior to each dose of study

- Anticipated requirement for anti-platelet or anti-coagulant agents excluding
non-aspirin NSAID within 48 hours following study treatment infusion


- 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

- 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

- No evidence of psychiatric illness/social situations

- Other illness that in the opinion of the investigator would exclude the patient from

- Must provide informed consent and HIPAA authorization and comply with
protocol-specified procedures and follow-up evaluations

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of ALT-836 in combination with gemcitabine

Outcome Time Frame:

18 months

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

May 2011

Completion Date:

October 2013

Related Keywords:

  • Locally Advanced Malignant Neoplasm
  • Malignant Solid Tumour
  • 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
  • Neoplasms



University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Carolinas Hematology-Oncology AssociatesCharlotte, North Carolina  28203
University of Rochester Medical Center, James P. Wilmot Cancer CenterRochester, New York  14642
Emory University, Winship Cancer InstituteAtlanta, Georgia  30322