Atezolizumab Monotherapy vs Atezolizumab Plus Cobimetinib in Liver Metastases From Colorectal Cancer

Withdrawn before enrolling · Phase 2

Conditions studied: Metastatic Colorectal Cancer

In brief

This study is for patients with metastatic colorectal cancer who are candidates for resection of metastases. This study will be conducted sequentially with 2 cohorts: 1.) Monotherapy Cohort and 2.) Combination Cohort Pre-metastatectomy * Monotherapy Cohort: The first 10 subjects will receive Atezolizumab 840 mg IV on Day 1 and Day 15 of each 28-day cycle. * Combination Cohort: The next 15 subjects will receive Atezolizumab 840 mg IV on Day 1 and Day 15 and Cobimetinib 60 mg PO on Days 1-21 of each 28-day cycle. Note: Cobimetinib must be held for the 7 days prior to metastatectomy. All subjects will be treated for 2 cycles (8 weeks) prior to metastatectomy Metastatectomy Subjects will undergo liver metastatectomy within 42 days of completion of Cycle 2 of pre-metastatectomy treatment. No study treatment is administered while the patient is healing after surgery. Post-metastatectomy Once the patient has healed from the surgery, adjuvant treatment may be administered at the discretion of the treating physician. Restaging following standards of care for this setting.

Key facts

Study ID: NCT03340558
Run by: Niharika Mettu
People needed: 0
Starts: 2018-05-01
Expected to finish: 2025-02-01
Last updated by the study team: 2018-10-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Histologically and/or cytologically confirmed and radiographically measurable per RECIST v1.1 colorectal cancer with liver metastasis. Patients may have other sites of metastatic disease.µlµ
Liver lesion safely amenable to core needle biopsy.
Willing to undergo core needle biopsy of liver metastatic site.
Microsatellite stable disease as determined by IHC and/or PCR.
Plan for next therapeutic intervention to be surgical resection of metastatic disease.
Age ≥18 years with ability to understand and willingness to provide informed consent.
ECOG performance status of 0 or 1.
Life expectancy of >3 months.
For Combination Therapy cohort only: Able to swallow pills.
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to start of study drug and must be willing to use two methods of contraception, one of them being a barrier method during the study and for 3 months (or 6 months for subjects on Combination Therapy cohort) after last study drug administration.
Adequate organ and marrow function as defined below:
Absolute neutrophil count (ANC) ≥1500 µl
WBC counts > 2500/µl
Lymphocyte count ≥ 300/µl
Platelets ≥ 100,000/µl
Hemoglobin (Hgb) ≥ 9 g/dL
Total bilirubin ≤ 1.5 x upper limit of normal (ULN); ≤ 3 x ULN for patients with known Gilbert disease
AST/ALT ≤ 3 x ULN without liver metastasis; ≤ 5 x ULN for patients with liver metastasis
Alkaline phosphatase ≤ 2.5 x ULN; ≤ 5 x ULN for patients with liver metastasis
Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation
INR and aPTT ≤ 1.5 x ULN. Note that this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.

You may not qualify if…

Prior therapy with anti-PD-1 or anti-PD-L1 therapeutic antibody or pathway targeting agents.
a. Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: i. Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose.
ii. No history of severe immune-related adverse effects from anti-CTLA-4 (NCI CTCAE Grade 3 and 4)
For Combination Therapy cohort only: Prior therapy with MEK inhibitors.
Anticancer therapy, including but not limited to chemotherapy, hormonal therapy, or radiotherapy, within 4 weeks prior to start of study treatment; however, the following are allowed:
Hormone-replacement therapy or oral contraceptives
Herbal therapy > 1 week prior to start of study treatment (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to start of study treatment)
Palliative radiotherapy for bone metastases > 2 weeks prior to start of study treatment
Expected to require any other form of systemic or localized anticancer therapy while on study.
Adverse events from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia.
Investigational agent within 4 weeks prior to start of study treatment (or within five half-lives of the investigational product, whichever is longer).
Major surgical procedure within 28 days prior to start of study treatment or anticipation of need for a major surgical procedure during the course of the study. This does not refer to the planned liver metastatectomy that is part of the study.
Malignancies other than the disease under study within 5 years prior to start of study treatment, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g. chronic lymphocytic leukemia Rai stage 0, prostate cancer with Gleason score < 6, and prostate-specific [PSA] ≤ 10 mg/mL, etc).
Diagnosis of acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma.
Prior allogenic bone marrow transplantation or prior solid organ transplantation.
Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases.
a. Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met: i. Evaluable or measurable disease outside the CNS ii. No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm) iii. No history of intracranial hemorrhage or spinal cord hemorrhage iv. No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.
v. No neurosurgical resection or brain biopsy within 28 days prior to start of study treatment b. Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following: i. Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study ii. No stereotactic radiation or whole-brain radiation within 28 days prior to start of study treatment iii. Screening CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids
Serious, non-healing wound, ulcer, or bone fracture.
Pregnancy, lactation, or breastfeeding
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or Chinese hamster ovary cell products.
History of malabsorption or other condition that would interfere with absorption of cobimetinib.
Bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis for osteoporosis) is allowed.
Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.

Where it is running

Duke University Medical Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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