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

Altor BioScience

Status and phase

Completed

Phase 1

Conditions

Locally Advanced Malignant Neoplasm

Malignant Solid Tumour

Treatments

Biological: ALT-836 in combination with gemcitabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT01325558

CA-ALT-836-02-10

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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