A Clinical Trials with a Combination of Investigational Prodcuts in Patients with Colorectal Cancer
- Conditions
- Microsatellite-stable (MSS) Metastatic Colorectal Cancer with RAS MutationMedDRA version: 20.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003464-12-GB
- Lead Sponsor
- Array BioPharma Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 90
Prescreening Inclusion Criteria:
1. Provide a signed and dated Prescreening ICF.
2. Male or female = 18 years of age at the time of signing the Screening ICF.
3. Measurable, histologically/cytologically confirmed mCRC per RECIST v1.1
4. Have willingness and ability to participate in the study.
5. Able to provide a sufficient amount (tumor block or minimum of 6 slides) of representative tumor specimen (primary or metastatic, archival or newly obtained) for central laboratory testing of RAS mutation status and MSS.
a. If a fresh tissue sample is provided, a blood sample is required.
6. Have received no more than 2 prior lines of systematic therapy in the metastatic setting (maintenance therapy given in the metastatic setting will not be considered a separate regimen). Generally, treatments that are separated by an event of progression are considered different regimens.
7. Have received prior systemic treatment as recommended by National Comprehensive Cancer Network (NCCN) or European Society for Medical Oncology (ESMO) guidelines, including fluoropyrimidines, oxaliplatin, irinotecan or bevacizumab in the metastatic setting or similar treatments, as per local guidelines.
8. No known contraindications to study treatment.
Screening Inclusion Criteria:
1. Patients must meet all Prescreening inclusion criteria.
2. Provide a personally signed and dated Screening ICF.
3. mCRC categorized as MSS by immunohistochemistry (IHC) or polymerase chain reaction (PCR)-based local assay at any time prior to Screening or by the central laboratory.
4. RAS mutation per local assay at any time prior to Screening or by the central laboratory.
5. Have received at least 1 prior line of systematic therapy in the metastatic setting as recommended by National Comprehensive Cancer Network (NCCN) or European Society for Medical Oncology (ESMO) guidelines, including fluoropyrimidines, oxaliplatin, irinotecan or bevacizumab, or similar treatments, as per local guidelines, and meets at least one of the following criteria:
a. were unable to tolerate the prior first-line regimen
b. experienced disease progression during or after prior first-line regimen for metastatic disease
c. progressed during or within 6 months of completing adjuvant chemotherapy
Note: Generally, treatments that are separated by an event of progression are considered different regimens.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
7. Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks; if a female patient is of childbearing potential, she must agree to follow instructions for acceptable or highly effective method(s) of contraception for the duration of study treatment and for 5 months after the last dose of study treatment with nivolumab (i.e., 30 days [duration of ovulatory cycle] plus the time required for the investigational drug to undergo approximately 5 half-lives)
8. Non-sterile male patients who are sexually active with female partners of childbearing potential must agree to follow instructions for acceptable or highly effective method(s) of c
Prescreening Exclusion Criteria:
1. Prior treatment with any MEK inhibitor.
2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
3. Any untreated central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery, and b) patients remained without evidence of CNS disease progression = 4weeks after treatment, and c) patients must be off corticosteroid therapy for = 3 weeks.
4. Patients with an active, known or suspected autoimmune disease, with the following exceptions: patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
5. Partial or complete bowel obstruction.
6. Impaired gastrointestinal function or disease that may significantly alter the absorption of binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) or baseline diarrhea = Grade 1.
7. Known history of RVO.
8. Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
9. Known history of Gilbert’s syndrome.
10. Severe uncontrolled medical illness.
11. Psychiatric illness inhibiting informed consent or protocol compliance.
12. Pregnant or breastfeeding females.
13. History of severe hypersensitivity reactions to mAbs.
14. History of allergy or intolerance (unacceptable AEs) to study drug components or polysorbate-80-containing infusions.
Screening Exclusion Criteria:
1. Patients must not meet any of the Prescreening exclusion criteria.
2. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to first day of study treatment:
a. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) and topical steroids are allowed. Patients who have received acute and/or low-dose systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or chronic use of = 10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the study after discussion with and approval by the Sponsor’s Medical Monitor.
3. Impaired gastrointestinal function or disease that may significantly alter the absorption of binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) or baseline diarrhea = Grade 1.
4. History of thromboembolic or cerebrovascular events = 6 months prior to starting study treatment, including transient ischemic at
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