The aim of this study is to see how well an investigational drug (called BBI-608) works when it is given in combination with a standard anticancer treatment for people with advanced colon or rectal cancer.
- Conditions
- Histologically confirmed adenocarcinoma of the colon or rectum that is metastatic (Stage IV).MedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001627-31-IT
- Lead Sponsor
- BOSTON BIOMEDICAL, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1250
1.1 Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable ICH guidelines and local and regulatory requirements prior to the performance of any study specific procedure.
1.2 Must have histologically confirmed advanced CRC that is metastatic.
1.3 Must have failed treatment with one regimen containing only a fluoropyrimidine and oxaliplatin with or without bevacizumab for metastatic disease. All patients must have received a minimum of 6 weeks of the first-line regimen that included oxaliplatin and a fluoropyrimidine with or without bevacizumab in the same cycle. Treatment failure is defined as radiologic progression during or < 6 months after the last dose of first-line therapy.
1.4 FOLFIRI therapy is appropriate for the patient and is recommended by the Investigator.
1.5 Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed within 21 days prior to randomization. Patients with either measurable disease or non-measurable evaluable disease are eligible.
1.6 Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
1.7 Must be = 18 years of age.
1.8 For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days for female and for male patients, of the final FOLFIRI dose. Patients who receive single agent BBI-608 without FOLFIRI must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days for female patients and 90 days for male patients, of the final BBI-608 dose. Female patients of child producing potential treated with bevacizumab, per investigator choice, must agree to use contraception or take measures to avoid pregnancy during the study and for 6 months, of the final bevacizumab dose.
1.9 Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG.
1.10 Must have alanine transaminase (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presence of liver metastases] within 14 days prior to randomization.
1.11 Must have hemoglobin (Hgb) = 9.0 g/dL within 14 days prior to randomization. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.
1.12 Must have total bilirubin = 1.5 × institutional ULN [= 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.
1.13 Must have creatinine = 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min as calculated by the Cockcroft-Gault equation (CKD-EPI equation may also be used) within 14 days prior to randomization.
1.14 Must have absolute neutrophil count = 1.5 x 109/L within 14 days prior to randomization.
1.15 Must have platelet count = 100 x 109/L within 14 days prior to randomization. Must not have required transfusion of platelets within 1 week of baseline platelet assessment.
1.16 Patient must have adequate nutritional status with Body Mass Index (BMI) > 18 kg/m2 and body weight of > 40 kg with serum albumin > 3 g/dL.
1.17 Other baseline laboratory evaluations must be done within 14 days prior to randomization.
1.18 Patient must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative formalin f
2.1 Anti-cancer chemotherapy or biologic therapy if administered prior to the first planned dose of study medication (BBI-608 or FOLFIRI) within period of time equivalent to the usual cycle length of the regimen. An exception is made for oral fluoropyrimidines (e.g. capecitabine, S-1), where a minimum of 10 days since last dose must be observed prior to the first planned dose of study medication.
2.2 More than one prior chemotherapy regimen administered in the metastatic setting.
2.3 Major surgery within 4 weeks prior to randomization.
2.4 Patients with any known brain or leptomeningeal metastases are excluded, even if treated.
2.5 Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of BBI-608 or while undergoing treatment with FOLFIRI and for 180 days after the last dose of FOLFIRI.
2.6 Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the
absorption of an oral agent (e.g. intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
2.7 Unable or unwilling to swallow BBI-608 capsules daily.
2.8 Prior treatment with BBI-608 or possible hypersensitivity to BBI-608 or one of the excipients which include azo dyes sunset yellow and allura red.
2.9 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
a. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B (patients who have had an HBV immunization are eligible), or hepatitis C.
b. Patients with clinically significant ascites or pleural effusions.
2.10 Known hypersensitivity to 5-fluorouracil/leucovorin
2.11 Known dihydropyrimidine dehydrogenase (DPD) deficiency
2.12 Known hypersensitivity to irinotecan
2.13 Chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis)
2.14 Patients receiving treatment with St. John's wort or Phenytoin.
2.15 Patients who plan to receive yellow fever vaccine during the course of the study treatment.
2.16 Abnormal glucuronidation of bilirubin, known Gilbert's syndrome
2.17 Patients with QTc interval > 470 milliseconds
2.18 For patients to be treated with a regimen containing bevacizumab: please refer to protocol
2.19 Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 3 years.
2.20 Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
2.21 Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
(Please refer to protocol for further information).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method