Safety Study of Recombinant NAPc2 to Prevent Tumor Progression and Metastases in Metastatic Colon Cancer

Study Overview
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Brief Summary
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This is a multicenter, two-stage trial with the goal of evaluating up to 100 subjects. This trial will be performed to initiate identification of a safe and effective dose of twice-weekly, subcutaneous rNAPc2 for the second-line treatment of metastatic colorectal carcinoma in combination with contemporary 5-FU-based chemotherapy.

Detailed Description
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Cytotoxic chemotherapy combining 5-fluorouracil and leucovorin with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) or, more recently, treatment with XELOX (Roche) (capecitabine + oxaliplatin) has been the main approach for the treatment of metastatic colorectal carcinoma (mCRC), but with the advent of targeted therapies, biologic treatments are becoming an area of intense interest. Tissue factor (TF) is a transmembrane glycoprotein expressed by upwards of 85% of mCRCs.

Official Title
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Multicenter, Two-Stage Study to Evaluate the Safety and Efficacy of Second-Line Metastatic Colorectal Carcinoma Treatment With Recombinant NAPc2

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: recombinant nematode anticoagulant protein c2 (rNAPc2)


Participation Criteria
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Eligibility Criteria
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Tissue diagnosis of adenocarcinoma of the colon or rectum Documented metastatic disease with at least one measurable lesion by RECIST criteria Previously treated with 5-FU-based chemotherapy in the form of FOLFIRI, FOLFOX, or XELOX plus bevacizumab as first-line chemotherapy and have recorded progressive disease during treatment or after discontinuation of treatment, when discontinuation of treatment occurred less than 6 months before enrollment (Stage I) or randomization (Stage II) Estimated life expectancy of at least 6 months Age 18 to 75 years Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before enrollment No other active malignancy for which the subject is currently receiving treatment (other than mCRC) No ongoing therapy with or need for parenteral and oral antithrombotics including anticoagulants and anti-platelet agents (including aspirin) and thrombolytics No contraindication to systemic anticoagulation No contraindication to modified FOLFOX6 or FOLFIRI combination chemotherapy No receipt of any investigational compound within 28 days of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: recombinant nematode anticoagulant protein c2 (rNAPc2)|escalating dose administered 2x/week sq.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by major hemorrhage (NCI CTCAE v3.0 grade 3 or greater), during and up to 30 days after completion of study drug administration or, if treatment is ongoing, by 8 months after study enrollment (Stage I) or randomization (Stage II) |  | 30 days after study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by adverse events |  | 30 days after study completion | 
| Efficacy measured by new metastasis-free survival by 8 months |  | 8 months | 
| Survival by 8 months |  | 8 months | 
| Arterial or venous thrombosis |  | 8 months | 
| Tumor response rate, as assessed by RECIST criteria |  | 30 days after study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leucovorin, metastatic colorectal carcinoma (mCRC), colorectal carcinoma (CRC), tissue factor, factor VIIa, rNAPc2, adenocarcinoma, targeted therapy, coagulation-dependent, RECIST, 5-FU-based chemotherapy, FOLFOX, FOLFIRI, XELOX