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

NCT01325558 | Completed Phase 1 DMC

• 1 other identifier: CA-ALT-836-02-10
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Locally Advanced Malignant Neoplasm; Malignant Solid Tumour

Keywords

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

Outcome Measures

Primary Outcomes (4)

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

  18 months

• Safety Profile

  Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment

  18 months

• Clinical Benefit

  Number of participants with complete response, partial response or stable disease

  18 months

• Progression Free Survival

  Number of participants with 9-month, 12-month, 18-month, 24-month, 30-month or 36-month progression-free survival

  36 months

Secondary Outcomes (2)

• Overall Survival

  36 months

• Pharmacokinetics

  18 months

Interventions

ALT-836 in combination with gemcitabine BIOLOGICAL

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Altor BioScience: lead

Study Sites (4)

Emory University, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Rochester Medical Center, James P. Wilmot Cancer Center

Rochester, New York, 14642, United States

Location

Carolinas Hematology-Oncology Associates

Charlotte, North Carolina, 28203, United States

Location

MeSH Terms

Conditions

Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Colonic Neoplasms; Pancreatic Neoplasms; Head and Neck Neoplasms; Prostatic Neoplasms; Sarcoma; Neoplasm Metastasis; Venous Thromboembolism

Interventions

ALT-836; Gemcitabine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Pancreatic Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2011
• First Posted: March 30, 2011
• Study Start: May 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: February 1, 2015
• Last Updated: July 15, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)