Atezolizumab + Cabozantinib in Patients w/ Metastatic, Refractory Pancreatic Cancer

Running, not enrolling · Phase 2

Conditions studied: Pancreatic Cancer, Metastatic Pancreatic Cancer

In brief

Pancreatic cancer is one of the leading causes of cancer deaths in the United States with limited treatment options, especially for those patients with metastatic disease. Combination treatment with cabozantinib and atezolizumab, has demonstrated safety for the treatment of other cancers and has shown promise in preclinical studies utilizing patient derived pancreas organoids. In this study, patients with refractory, metastatic pancreatic cancer will receive combination cabozantinib + atezolizumab and the efficacy of this treatment will be assessed through overall response rate (ORR), disease control rate (DCR), median overall survival (mOS), and median progression free survival (mPFS). Safety and tolerability of combination cabozantinib plus atezolizumab in metastatic pancreatic cancer patients will also be assessed and immune profiling pre- and post-treatment will be explored.

Key facts

Study ID

NCT04820179

Run by

University of Arizona

People needed

30

Starts

2021-10-12

Expected to finish

2027-01-31

Last updated by the study team

2026-04-02

Who can join

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

You may qualify if…

• Stage IV pancreatic adenocarcinoma, confirmed by histology or cytology. (Note: the primary pancreatic adenosarcoma must be confirmed by histology or cytology. The stage IV metastatic disease does not necessarily need to be confirmed by histology or cytology).
• Clinical and/or radiographic progression on and/or intolerance to and/or ineligibility for treatment with at least one of the following: a fluoropyrimidine or gemcitabine based chemotherapy treatment regimens
• Radiographically measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Images (MRI or CT Scan) must be completed within 28 days prior to treatment start.
• Age ≥ 18 years
• Patients who progress on adjuvant treatment and develop metastatic disease within < 6 months of adjuvant therapy will be considered as having one prior line of treatment and may be eligible pending subject meeting all other inclusion/exclusion criteria.
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support.
• White blood cell count ≥ 2500/µL
• Platelets ≥ 100,000/µL without transfusion.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions:
• Patients with documented liver metastases: AST and ALT ≤ 5 x ULN Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
• Serum albumin ≥ 2.8 g/dl
• (PT)/INR or partial thromboplastin time (PTT) test < 1.3 x the laboratory ULN
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation:
• Males: (140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72) Females: [(140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g
• For patients receiving therapeutic anticoagulation, they must have a stable anticoagulant regimen.
• No clinically significant hypertension as per treating physician or if hypertension, adequate control with anti-hypertensives
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test.
• ECOG performance status ≤ 1
• Recovered to baseline or to CTCAE v5.0 ≤ Grade 1 treatment-related toxicity from prior therapies
• At least two weeks since last dose of prior treatment

You may not qualify if…

• Prior treatment with cabozantinib.
• Prior treatment with atezolizumab and/or CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 28 days before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a) Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
• iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
• iv. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #6) for at least 1 week before first dose of study treatment.
• b) Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.
• iii. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• Lesions invading or encasing any major blood vessels.
• History of leptomeningeal disease
• Uncontrolled tumor-related pain
• Patients requiring pain medication must be on a stable regimen at study entry.
• Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.

Where it is running

• University of Arizona Cancer Center — Tucson, Arizona, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.