Evaluating Novel Therapies in ctDNA Positive GI Cancers

Recruiting now · Phase 3

Conditions studied: Colon Adenocarcinoma, Rectal Adenocarcinoma, Gastric Adenocarcinoma, Pancreatic Adenocarcinoma, Hepatocellular Carcinoma, Adenocarcinoma of Biliary Tract, Gallbladder Adenocarcinoma

In brief

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.

Key facts

Study ID

NCT05482516

Run by

Georgetown University

People needed

20

Starts

2023-03-29

Expected to finish

2028-12-01

Last updated by the study team

2025-05-22

Who can join

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

You may qualify if…

• 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.
• Must have been diagnosed with any stage disease (including localized and metastatic disease) that was felt to have already been treated completely with curative-intent per investigator's, primary physician's, or research team's judgement. Curative-intent treatment strategies are unique to each tumor type and stage but includes all surgeries and perioperative therapies recommended. If patients were appropriately treated with curative intent but felt to be high-risk for relapse, they may be still be included.
• o Patients diagnosed with hepatocellular carcinoma specifically must have Child Pugh A score at the time of screening; o Patients must have completed all definitive SOC treatment with curative intent (neoadjuvant, surgery, radiation, and adjuvant treatments) for specific tumor-type and stage per investigator's/primary physician's or research team's judgment. Curative treatment regimens including chemotherapy, radiation, treatment sequencing, and surgery should have been followed as per local standards and NCCN guidelines or non-standard curative-intent therapy through a clinical trial at the discretion of the investigator/treating physician.
• Patients who have undergone definitive, curative-intent treatment of oligometastatic (synchronous or metachronous) disease with NED per investigator judgement are acceptable for enrollment.
• Must have disease-free status documented by complete physical examination and imaging studies with no evidence of recurrent, residual, or metastatic disease on standard imaging (chest, abdomen, and pelvis captured by CT chest and CT or MRI of abdomen and pelvis) per investigator assessment within 28 days prior to enrollment
• Must have a tumor-specific ctDNA SignateraTM test with a positive result (any mean tumor molecule/mL) drawn within 1 year of completing all curative-intent treatment and within 28 days prior to enrollment. In the setting of a negative scan for recurrence, this will be defined as subclinical molecular disease.
• ECOG Performance Status of 0-2
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 28 days prior to initiation of study treatment:
• ANC ≥1.5 x 109/L (1500/uL) without granulocyte colony-stimulating factor support
• Lymphocyte count ≥ 0.5 x 10\^9/L (500/uL)
• Platelet count ≥ 75 x 10\^9/L (75,000/uL) without transfusion
• Hemoglobin ≥ 90 g/L (9 g/dL) Patients may be transfused to meet this criterion.
• AST, ALT, and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN)
• Note: for HCC, AST, ALT, and alkaline phosphatase (ALP) ≤ 5 x upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 x ULN with the following exception: Patients with known Gilbert disease or HCC: serum bilirubin ≤3 x ULN
• Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
• Urine dipstick for proteinuria < 2 + (if ≥ 2+ proteinuria on dipstick urinalysis, patient should undergo 24-hour urine collection and must demonstrate < 1 g protein in 24 hours).
• Serum albumin ≥ 25 g/L (2.5 g/dL). Cut-off of ≥ 28 g/L (2.8 g/dL) will be used for HCC patients.
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN. Note: for HCC patients INR or aPTT should be ≤ 2 x ULN.
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200µL, and have an undetectable viral load.
• Select patients with well compensated, treated HBV infection and chronic HCV infection may be considered

You may not qualify if…

• 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.
• Active tuberculosis
• Clinically significant cardiovascular disease, such as cerebrovascular accidents within 12 months prior to randomization, myocardial infarction within 12 months prior to study treatment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with study treatment.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization.
• Inadequately controlled hypertension (defined as systolic blood pressure >150mmHg and/or diastolic blood pressure >100 mmHg), based on an average of ≥ 3 BP blood pressure readings on ≥ 2 sessions. Anti-hypertensive therapy to achieve these parameters is allowable.
• History of hypertensive crisis or hypertensive encephalopathy
• History of Grade ≥ 4 venous thromboembolism
• History or evidence upon physical or neurological examination of central nervous system bleed
• History of Grade ≥ 2 hemoptysis (defined as ≥ 2.5 mL of bright red blood per episode) within 1 month prior to screening.
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation).
• Current or recent (<10 days prior to initiation of study treatment) use of aspirin (>325 mg/day), or clopidogrel (>75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. For prophylactic use of anticoagulants or thrombolytic therapies, local label approved dose levels may be used. The use of direct oral anticoagulant therapies such as dabigatran (Pradaxa) and rivaroxaban (Xarelto) is not recommended due to bleeding risk.
• Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID); o Occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or joint pain is allowed.
• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to initiation of study treatment, or anticipation of need for major surgical procedure during the course of the study.
• Local therapy to liver or other organ (e.g. radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization, etc.) within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding in high-risk patients (patients with HCC, cirrhosis, or other conditions predisposing patients to high-risks of portal hypertension).
• High risk patients must undergo an esophagogastroduodenoscopy (EGD) and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months prior to initiation of study treatment do not need to repeat the procedure.
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of study treatment.
• Placement of a vascular access device should be at least 2 days prior to initiation of study treatment.
• Active infection requiring IV antibiotics at the time of initiation of study treatment.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety
• History of abdominal fistula, GI perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to study treatment. o If GI bleeding was from a lesion or a condition that was appropriately treated and patient is deemed to be low risk for recurrent GI bleed per investigator judgement, enrollment will be allowed.

Where it is running

• Georgetown Lombardi Comprehensive Cancer Center — Washington D.C., District of Columbia, United States (enrolling)
• Medstar Washington Hospital Center — Washington D.C., District of Columbia, United States (enrolling)
• John Theurer Cancer Center at Hackensack University Medical Center — Hackensack, New Jersey, United States (enrolling)

Full record on ClinicalTrials.gov

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