This study is a non-randomized, open-label, multi-cohort, multi-site, pilot feasibility therapeutic trial. The study will enroll 20 patients across 4 cohorts (CRC, gastric, PDAC, and HCC/intra-hepatic-/extra-hepatic-, gall bladder adenocarcinomas) diagnosed with histologically confirmed GI cancers. These patients will have already completed all Standard of Care (SOC) treatments (including neoadjuvant, surgery, local therapies, and/or adjuvant therapy as applicable), as defined by the treating primary physician or research team, with curative intent but have a positive SignateraTM tumor-informed ctDNA test and NED radiographically by standard imaging within 28 days prior to enrollment and within 1 year of completing all curative-intent therapy. All patients will be treated with intravenous (IV) atezolizumab 1200 mg IV and bevacizumab 15 mg/kg on Day 1 of 21-day cycles until disease recurrence, ctDNA POD, unacceptable toxicity, or subject withdrawal of consent with a maximum 12 month total duration of study therapy. Atezolizumab and bevacizumab drug will be provided.
Signed Informed Consent Form
Age >= 18 years at time of signing Informed Consent Form
Ability to comply with the study protocol, in the investigator's judgment
Histologically or cytologically confirmed colorectal adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, hepatocellular carcinoma, or extra-hepatic/intra-hepatic/gallbladder adenocarcinoma. Patients may be enrolled irrespective of any mutational analyses.
There is suspicion or evidence of gross residual, recurrent, or metastatic disease present on physical exam, imaging, or by biopsy within 28 days of starting study treatment.
Patients who were/are eligible for but have not received all guideline-recommended standard of care therapy within the recommended time-frame for definitive treatment. The exception (permitting inclusion) would be if any standard of care treatment was deferred due to valid medical reasoning based on the investigator's discretion or patient's preference.
Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix 6 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions: o Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. o Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. o Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: - Rash must cover < 10% of body surface area; - Disease is well controlled at baseline and requires only low-potency topical corticosteroids; - No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Single group
Atezolizumab
DrugAtezolizumab is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway,
Bevacizumab
DrugBevacizumab is a tumor-starving (anti-angiogenic) therapy. Avastin is designed to block a protein called vascular endothelial growth factor, or VEGF.
Rates of SignateraTM ctDNA positive Patient identification
The number of local and regional SignateraTM ctDNA positive patients identified over 12 months in the setting of NED after all SOC definitive therapies (identified patients). This data will be obtained on a local and regional level through the SignateraTM company, Natera.
Rate of Enrollment
Percentage and absolute number of contacted patients who ultimately enrolled on trial (enrolled patients)
Rate of ctDNA Complete Response (CR)
Percentage of patients in each cohort (and collectively) who achieve ctDNA CR (defined as ctDNA clearance on two sequential tests compared to baseline ctDNA and ongoing NED clinically/radiographically) within 12 weeks ± 14 days of study therapy.
Rate of ctDNA Partial Response (PR)
Percentage of patients in each cohort (and collectively) who achieve ctDNA PR (ctDNA does not clear on two sequential tests, ctDNA does not double on each of two consecutive tests, does not increase on each of three consecutive tests, and ongoing NED clinically/radiographically) within 12 weeks ± 14 days of study therapy.
Toxicity by CTCAE v5.0 criteria
Toxicity and safety analysis will occur in patients who received at least one full or partial dose of study treatment. Adverse events will be graded per NCI CTCAE v.5.0.
Reasons for failure of enrollment
Reasons for failure of enrollment characterized as patient preference, physician preference, or ineligibility, among others of identified and contacted patients will be reported
Click on the lead sponsor to view all of their trials.
