A Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors
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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 |
- 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
- 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: | October 2013 |
| Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
-
Biological: ALT-836 in combination with gemcitabine
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 |
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| 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 | |
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: | March 11, 2013 |
| 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 May 22, 2013