Evaluating Novel Therapies in ctDNA Positive GI Cancers

NCT05482516 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: STUDY00005282ML43975
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Colon Adenocarcinoma; Rectal Adenocarcinoma; Gastric Adenocarcinoma; Pancreatic Adenocarcinoma; Hepatocellular Carcinoma; Adenocarcinoma of Biliary Tract; Gallbladder Adenocarcinoma

Outcome Measures

Primary Outcomes (5)

• 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.

  12 months

• Rate of Enrollment

  Percentage and absolute number of contacted patients who ultimately enrolled on trial (enrolled patients)

  12 months

• 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.

  12 weeks from start of treatment

• 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.

  12 weeks from start of treatment

• Rate of ctDNA Progression of Disease (POD) or Clinical/radiographic Relapse

  Rate of ctDNA POD or clinical/radiographic relapse is defined as the percentage of patients in each cohort (and collectively) who experience ctDNA doubling (at least) on each of two consecutive, sequential tests using the prior ctDNA value as the reference point for doubling for each test, ctDNA rise on each of three consecutive ctDNA tests using the prior ctDNA value as the reference point for each test (ctDNA POD), or clinical/radiographic relapse within 12 weeks ± 14 days of study therapy.

  12 weeks from start of treatment

Secondary Outcomes (2)

• Toxicity by CTCAE v5.0 criteria

  12 months

• Reasons for failure of enrollment

  12 months

Study Arms (1)

Atezolizumab plus Bevacizumab

EXPERIMENTAL

atezolizumab 1200 mg and bevacizumab 15 mg/kg given intravenously on Day 1 of each 21-day cycle (every 3 weeks \[Q3W\]) for a maximum of 12 months.

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Atezolizumab 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,

Also known as: TECENTRIQ

Atezolizumab plus Bevacizumab

Bevacizumab DRUG

Bevacizumab is a tumor-starving (anti-angiogenic) therapy. Avastin is designed to block a protein called vascular endothelial growth factor, or VEGF.

Also known as: Avastin

Atezolizumab plus Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.
• 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.

Sponsors & Collaborators

• Georgetown University: lead
• Genentech, Inc.: collaborator
• Natera, Inc.: collaborator

Study Sites (3)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• John L. Marshall, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Loyanna Hubbard

CONTACT

202-784-0038; lh1065@georgetown.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: August 1, 2022
• Study Start: March 29, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 22, 2025

Record last verified: 2025-05

Locations

US (3)