Cabozantinib in Combination With Pembrolizumab for the Treatment of Patients With Locally Advanced, Metastatic, or Unresectable Adrenal Cortical Cancer

Recruiting now · Phase 2

Conditions studied: Locally Advanced Adrenal Cortex Carcinoma, Adrenal Cortical Carcinoma, Stage III Adrenal Cortex Carcinoma, Stage IV Adrenal Cortex Carcinoma AJCC v8, Unresectable Adrenal Cortex Carcinoma

In brief

This phase II trial tests how well cabozantinib in combination with pembrolizumab works in treating patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), that has spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Cabozantinib inhibits receptor tyrosine kinases, which are receptors commonly over-expressed by tumor cells. This may result in an inhibition of both tumor growth and blood vessel formation, eventually leading to a decrease in tumor size or extent in the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Adding cabozantinib to pembrolizumab may be more effective at treating patients with adrenal cortical cancer than giving these drugs alone.

Key facts

Study ID: NCT06006013
Run by: Emory University
People needed: 21
Starts: 2025-01-15
Expected to finish: 2028-12-16
Last updated by the study team: 2026-02-18

Who can join

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

You may qualify if…

Male or female
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 ,Karnofsky >= 50%.
Metastatic disease or unresectable locally advanced disease.
Histologically documented adrenal cortical carcinoma.
Untreated or having received any number of lines of prior therapy.
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
Life expectancy >= 12 weeks
Tumor tissue samples must be available for submission prior to initiation of study treatment. If not, agree to undergo biopsy.
Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version 5 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy.
Absolute neutrophil count (ANC) >= 1500/uL without granulocyte colony-stimulating factor support within 28 days before first dose of study treatment.
Lymphocyte count 0.5 x 10\^9/L (500/mL) within 28 days before first dose of study treatment.
White blood cell count >= 2500/uL within 28 days before first dose of study treatment.
Platelets >= 100,000/uL without transfusion within 28 days before first dose of study treatment.
Hemoglobin >= 9 g/dL (>= 90 g/L). Patients may be transfused to meet this criterion within 28 days before first dose of study treatment.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =< 3 x upper limit of normal (ULN). ALP =< 5 x ULN with documented bone metastases within 28 days before first dose of study treatment.
Total bilirubin =< 1.5 x ULN for subjects with Gilbert's disease =< 3 x ULN within 28 days before first dose of study treatment.
Serum albumin >= 2.8 g/dl within 28 days before first dose of study treatment.
Prothrombin time (PT) / international normalized ratio (INR) or partial thromboplastin time (PTT) test < 1.3 x the laboratory ULN within 28 days before first dose of study treatment.
Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 40mL/min (>= 0.675mL/sec) using the Cockcroft-Gault equation within 28 days before first dose of study treatment.
Urine protein/creatinine ratio (UPCR) =< 1 mg/mg (=< 113.2 mg/mmol), or 24-h urine protein =< 1 g within 28 days before first dose of study treatment.
Negative human immunodeficiency virus (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 >= 200/uL, and have an undetectable viral load.
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 hepatitis C virus (HCV) ribonucleic acid (RNA) test at screening.
The hepatitis C virus (HCV) ribonucleic acid (RNA) test must be performed for patients who have a positive HCV antibody test

You may not qualify if…

Receipt of any type of small molecule kinase inhibitor including investigational kinase inhibitor within 2 weeks before first dose of study treatment
Prior treatment with 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 cytotoxic, biologic or other systemic anticancer therapy (including immunostimulatory agents or investigational agents) within 4 weeks or 5 half-lives of the drug (whichever is longer) 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 with known brain metastases or cranial epidural disease should also have no history of intracranial hemorrhage or spinal hemorrhage. 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. If subject is receiving anti-convulsant therapy, the dose is considered stable
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
Administration of a live, attenuated vaccine within 30 days before first dose of study treatment or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
Concomitant mitotane use
Mitotane must have been discontinued 28 days prior to first dose of study treatment, with mitotane serum level < 2 mg/L if mitotane administered within last 6 months
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
Cardiovascular disorders:
Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias
Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment
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
Subjects with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep vein thrombosis (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
Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
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
Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment
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 (see exclusion criteria #4 for minimal required duration prior to trial enrollment)
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
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

Where it is running

Emory University Hospital Midtown — Atlanta, Georgia, United States (enrolling)
Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States (enrolling)

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.