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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: GM-CT-01
* Drug: 5-Fluorouracil, Leukovorin, bevacizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GM-CT-01<br> | Drug: GM-CT-01<br>* 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 .)<br>* Other names: DAVANAT;Drug: 5-Fluorouracil, Leukovorin, bevacizumab<br>* 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.<br>* Other names: 5-FU, LV, Avastin®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, DAVANAT, colon cancer, 5-FU