Actively Recruiting
Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies
Led by Anwaar Saeed · Updated on 2026-01-21
117
Participants Needed
2
Research Sites
557 weeks
Total Duration
On this page
Sponsors
A
Anwaar Saeed
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
The investigators propose to evaluate the safety of drug combinations in patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies. Finding effective novel therapies for patients with advanced gastric cancer and other GI malignancies is an area of great unmet need. The investigators believe that modulating the tumor microenvironment with biologic agents like cabozantinib will have synergistic effect when combined with checkpoint-based immunotherapeutics like durvalumab in this patient population. This is a phase I/II, open label, multi-cohort trial looking at safety, tolerability and efficacy endpoints.
CONDITIONS
Official Title
Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
- Histologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma, esophageal adenocarcinoma, colorectal adenocarcinoma, or hepatocellular carcinoma
- Advanced (stage IV) or locally unresectable (stage III) disease
- Measurable disease per RECIST version 1.1 criteria
- Willingness to undergo required tumor biopsies at screening/baseline and possibly at disease response or progression
- For gastric, gastroesophageal, or esophageal adenocarcinoma: progression or intolerance to at least one prior standard systemic therapy
- For colorectal cancer: progression or intolerance to at least two prior standard systemic therapies; Ras wild type patients must have failed EGFR monoclonal antibody therapy
- For hepatocellular carcinoma cohort 3: progression or intolerance to at least one prior systemic regimen (maximum two lines of prior therapy)
- For hepatocellular carcinoma cohort 4: treatment-naïve or progression or intolerance to at least one prior systemic regimen (maximum two lines of prior therapy)
- Known tumor microsatellite instability (MSI) or mismatch repair (MMR) status or agreement to testing
- Recovery to baseline or no greater than Grade 1 toxicity from prior treatments unless clinically nonsignificant or stable on supportive therapy
- Body weight greater than 66 pounds (30 kg)
- Adequate organ and marrow function
- Post-menopausal status or negative pregnancy test for pre-menopausal women
- Agreement to use effective contraception during and for 180 days after study participation for women of child-bearing potential and men with partners of child-bearing potential
- Men must agree not to donate sperm during study and for 180 days after last treatment
You will not qualify if you...
- Prior treatment with PD-1 or PD-L1 inhibitors, including durvalumab, except for HCC and gastric/esophageal cancer patients
- Prior treatment with cabozantinib or other MET/HGF monoclonal antibodies or tyrosine kinase inhibitors
- Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose
- Tumor invading the gastrointestinal tract (T4 primary tumor) in gastric, gastroesophageal, esophageal adenocarcinoma, or colorectal cancer
- Untreated or incompletely treated gastric or esophageal varices with bleeding or high bleeding risk
- Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, or gastric outlet obstruction
- Inability to swallow tablets
- Uncontrollable ascites or pleural effusion
- Cavitating pulmonary lesions or known endotracheal/endobronchial disease
- Significant bleeding history or pulmonary hemorrhage within specified timeframes
- Lesions invading major blood vessels (except hepatic portal vasculature in HCC)
- Unresolved toxicity Grade 2 or higher from prior cancer therapy
- Extensive radiotherapy to bone marrow or wide-field radiation within 4 weeks of first dose
- Major surgery within 8 weeks before first dose
- Recent use of immunosuppressive medication except some corticosteroids
- History of allogenic organ transplantation
- Active or prior autoimmune or inflammatory disorders
- History of primary immunodeficiency
- Active infection including tuberculosis, hepatitis B or C, HIV (with exceptions for some HCC patients)
- Receipt of live attenuated vaccine within 30 days prior to first dose
- Uncontrolled hypertension despite treatment
- Recent stroke, myocardial infarction, ischemic or thromboembolic events within 6 months
- Untreated central nervous system metastases or carcinomatous meningitis
- Clinically significant disorders precluding safe participation
- History of other primary malignancy with exceptions for treated and inactive conditions
- Concomitant anticoagulation with oral anticoagulants or platelet inhibitors except certain low-dose or stable low molecular weight heparins
- Known allergy or hypersensitivity to study drugs or their components
AI-Screening
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Trial Site Locations
Total: 2 locations
1
University of Kansas Cancer Center
Westwood, Kansas, United States, 66205
Terminated
2
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
Research Team
D
Debra Diecks, RN
CONTACT
C
Clare Grzejka, RN
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
4
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