Colon Cancer
Conditions
Keywords
metastatic colorectal carcinoma (mCRC), colorectal carcinoma (CRC), tissue factor, factor VIIa, rNAPc2, adenocarcinoma, targeted therapy, coagulation-dependent, RECIST, 5-FU-based chemotherapy, FOLFOX, FOLFIRI, leucovorin, XELOX
Brief summary
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
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.
Interventions
DRUGrecombinant nematode anticoagulant protein c2 (rNAPc2)
escalating dose administered 2x/week sq.
Sponsors
ARCA Biopharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed