A clinical study that will test whether cobimetinib plus atezolizumab and atezolizumab alone are effective and safe in patients with colorectal cancer that has spread when compared to regorafenib
- Conditions
- The patient population are patients with metastatic or locally advanced unresectable colorectal adenocarcinoma that have received at least two lines of chemotherapy in this setting. The patients must have received 5-FU, oxaliplatin, and irinotecan. Patients who have received an anti-VEGF and anti-EGFR are eligible.MedDRA version: 20.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000202-11-BE
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 363
Disease specific inclusion criteria:
• Histologically confirmed adenocarcinoma originating from the colon or rectum (Stage IV American Joint Committee on Cancer 7th edition)
• Experienced disease progression on at least two prior systemic chemotherapy regimens for mCRC
1. Prior systemic cytotoxic chemotherapy must include ALL of the following agents:
a) Fluoropyrimidines
b) Irinotecan
c) Oxaliplatin
2. Patients who have received prior anti-angiogenic therapy (e.g., bevacizumab) and/or anti epidermal growth factor receptor therapy (e.g., cetuximab) are eligible.
3. Patients must have had documented disease progression within 3 months of the last systemic therapy administration.
4. Patients who were intolerant to prior systemic chemotherapy regimens are eligible if there is documented evidence of clinically significant intolerance despite adequate supportive measures.
5. For patients who had disease recurrence within 6 months of completing adjuvant chemotherapy, the adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease.
General inclusion criteria:
• Signed Informed Consent Form
• Age = 18 years
• In the investigator’s judgment, patient is able to comply with the requirements and assessments of the study protocol
•Eastern Cooperative Oncology Group performance status of 0 or 1
•Anticipated life expectancy = 3 months
•Able to comply with the requirements and assessments of the study protocol
•Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to first dose of study drug treatment:
1.Hemoglobin = 9 g/dL, platelet count = 100,000/mm3, ANC = 1500/mm3
2.Creatinine clearance = 30 mL/min
3.Amylase and lipase = 1.5 x the upper limit of normal (ULN)
4.Serum bilirubin = 1.5x ULN; patients with known Gilbert’s disease may have a bilirubin = 3.0x ULN
5.AST, ALT, and alkaline phosphatase (ALP) = 2.5 ULN with the following exceptions:
a)Patients with documented liver metastases: AST and/or ALT = 5 x ULN
b)Patients with documented liver or bone metastases: ALP = 5 x ULN
6.INR and PTT = 1.5 x ULN. Patients who are on therapeutic doses of anti coagulants are eligible if they are on a stable dose of anti-coagulant for 28 days with stable INR and PTT values.
•Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of < 1% per year) during the treatment period, within 5 months after the last dose of atezolizumab, and within 3 months after the last dose of cobimetinib and regorafenib
7.A woman of childbearing potential is defined as a sexually mature woman without prior oophorectomy or hysterectomy who have had menses within the last 12 months.
8.A woman is not considered to be of childbearing potential if she has become amenorrheic for > 12 months and has a follicle stimulating hormone level = 40 IU/L.
•Men must agree not to donate sperm or have intercourse with a female partner without using appropriate barrier c
Cancer-related exclusion criteria:
•After the approximate 5% cap for MSI-high patients is reached, only MSI-stable patients will be eligible.
•Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment.
•Treatment with any anti-cancer agent within 14 days prior to Cycle 1 Day 1
•Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry.
•Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX ) are allowed.
•Active or untreated CNS metastases are excluded. Patients with treated and asymptomatic CNS metastases are eligible,
•Exclusion criteria related to study medication:
Any cancer immunotherapy including CD137 agonists, anti-programmed death-1, anti PD L1, or anti CTLA4; Any MEK or ERK inhibitor; and Regorafenib
•Patients with active malignancy (other than CRC) or a prior malignancy within the past 3 years are excluded. Patients with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible.
Exclusion criteria based on organ function or medical history:
Cardiovascular:
•Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure New York Heart Association Class II or higher.
•Left ventricular ejection fraction below institutional lower limit of normal or below 50%, whichever is lower.
•Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 mmHg despite optimal medical management.
Infections:
•HIV infection
•Severe infections within 2 weeks prior to Cycle 1 Day 1
•Signs or symptoms of significant infection within 2 weeks prior to Cycle 1 Day 1
•Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
•Active or chronic viral hepatitis B or C infection
Ocular:
•History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion, or neovascular macular degeneration
•Patients will be excluded if they currently have risk factors for retinal vein occlusion
Autoimmune conditions and immunomodulatory drugs:
•History of autoimmune disease
•History of idiopathic pulmonary fibrosis, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis
Other medical conditions or medications:
•Any hemorrhage or bleeding event CTCAE Grade 3 or higher within 28 days of Cycle 1 Day 1
•Foods, supplements or drugs that are potent CYP3A4 enzyme inducer or inhibitors are prohibited at least 7 days prior to Cycle 1 Day 1 and during study treatment. General exclusion criteria:
•Inability to swallow medications
•Ma
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