A New Agent GM-CT-01 in Combination With 5-FU, Avastin and Leucovorin in Subjects With Colorectal Cancer

Open-Label, Phase 2 Study of GM-CT-01 When Added to a Regimen of Leucovorin, 5-FU, and Avastin as First Line Treatment for Locally Advanced, Unresectable or Metastatic Colorectal Cancer in Subjects Unable to Tolerate Intensive Chemotherapy

The purpose of this clinical trial is to determine whether the combination of 5-fluorouracil (5-FU) plus a DAVANAT (carbohydrate polymer) along with Avastin and Leucovorin (LV) is beneficial in treating colorectal cancer in patients unable to tolerate intensive chemotherapy.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: GM-CT-01; Drug: 5-Fluorouracil, Leukovorin, bevacizumab

Detailed Description

This is a Phase II, multi-center study of DAVANAT which has been shown to increase the anti-tumor activity of 5-FU in mice. 5-FU is a chemotherapy drug commonly used to treat tumors. A Phase I study of 40 patients showed that DAVANAT in different doses plus 5-FU was well tolerated in patients with different types of solid tumors who failed standard, approved treatments.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Rechovot, Israel
    • Kaplan MC
  • Tel Hashomer, Israel, 52621
    • Sheba MC
  • Tel-Aviv, Israel, 64239
    • Sourasky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older.
• Histologically confirmed, unresectable, locally advanced or metastatic colorectal adenocarcinoma (stage III and IV), not amenable to curative surgery or radiotherapy.
• Intolerant of oxaliplatin and/or irinotecan, as demonstrated by unacceptable toxicity after a trial of these agents as first-line therapy, or in the opinion of the Investigator, be judged at high risk for unacceptable toxicity to oxaliplatin and/or irinotecan,
• Presence of at least 1 measurable lesion,
• Have a life expectancy of at least 4 months.
• Women of childbearing potential, have a negative serum pregnancy test at screening and Day 1 treatment and agree to practice abstinence or use an effective method of contraception.

Exclusion Criteria:

• Central nervous system metastasis.
• Bony metastasis as the sole metastasis.
• Received any prior first-line chemotherapy for colorectal cancer.
• Previously exposed to DAVANAT® or Avastin®.
• Known or clinically suspected infection with HIV.
• Participated within 30 days or will participate concurrently in another investigational drug or vaccine study.
• History of drug or alcohol dependence in the past 3 years.
• Other serious, non-malignant, significant, acute or chronic medical or psychiatric illness that in the judgment of the Investigator could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GM-CT-01

Drug: GM-CT-01; On Day 1 and 2 of each cycle, GM-CT-01 280 mg/m2 administered IV over 30 minutes with 5-FU (400 mg/m2), followed by a 22-hour continuous infusion of GM-CT-01 (280 mg/m2) with 5-FU (600 mg/m2 .); Other Names: DAVANAT; Drug: 5-Fluorouracil, Leukovorin, bevacizumab; On Day 1 and 2 of each cycle, LV (200 mg/m2) will be administered IV over 2 hours, followed by 5-FU 400 mg/m2 in solution with GM-CT-01 280 mg/m2 administered over 30 minutes, followed by a 22-hour continuous infusion of GM-CT-01 (280 mg/m2) and 5-FU (600 mg/m2 ). on Day 3 Avastin® (5 mg/kg)will be given IV over 30 to 90 minutes per the package insert.; Other Names: 5-FU, LV, Avastin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcomes: Assess the efficacy and safety of GM-CT-01 administered with 5-FU, LV, and Avastin® in the first-line treatment of unresectable, locally advanced, and/or metastatic CRC.	To assess the clinical benefit of a regimen of GM-CT-01/5-FU, LV plus Avastin® when administered intravenously as a first-line treatment to patients with Stage III or IV ,advanced or metastatic CRC. Clinical activity will be assessed by determining the percentage of subjects exhibiting an objective response (complete response [CR]) plus partial response [PR]). Tumor response will be assessed following Response Evaluation by RECIST guidelines.	When 17 evaluable patients will complete the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of the DAVANAT®/5-FU, LV plus Avastin® regimen.	Assess safety of regimen and also patient reported outcomes using a Quality of Life (QoL) instrument.	Throughout the study and when 17 evaluable patients will when complete the study
Explore progression-free survival (PFS) and survival	To explore time to tumor progression, duration of response and and survival at 6 and 12 months after the first dose of study drug.	When at least 17 evaluable patients complete the study

Collaborators and Investigators

• Sponsor: Galectin Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: October 13, 2006
• First Submitted That Met QC Criteria: October 13, 2006
• First Posted (Estimate): October 17, 2006

Study Record Updates

• Last Update Posted (Actual): February 14, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Colorectal cancer, DAVANAT, colon cancer, 5-FU
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Leucovorin
• Other Study ID Numbers: DAVFU006