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

NCT06006013 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00005532NCI-2023-04952WINSHIP5823-22P30CA138292
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Locally Advanced Adrenal Cortex Carcinoma; Adrenal Cortical Carcinoma; Stage III Adrenal Cortex Carcinoma; Stage IV Adrenal Cortex Carcinoma AJCC v8; Unresectable Adrenal Cortex Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Overall response rate is defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors version 1.1. Overall response rate will be estimated by the Clopper-Pearson method with 95% confidence intervals. Descriptive statistics on continuous data will include means, medians, standard deviations, and ranges, while categorical data will be summarized using frequency counts and percentages. Will explore whether the sample size can inform on the association between overall response rate and demographics or molecular biomarkers by Fisher's exact test -categorical variables and Wilcoxon rank-sum test -continuous variables, wherever appropriate this analysis is exploratory in nature.

  Every 12 weeks, assessed up to 2 years

Secondary Outcomes (3)

• Progression free survival

  From treatment initiation until disease progression, death due to disease, or lost to follow up, assessed up to 2 years

• Overall survival

  From treatment initiation until death due to any cause or loss to follow up, assessed up to 2 years

• Incidence of adverse events

  Up to 2 years

Study Arms (1)

Treatment (cabozantinib, pembrolizumab)

EXPERIMENTAL

Patients receive cabozantinib orally (PO) once daily (QD) on days 1-21 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) at screening and then every 12 weeks on study and undergo collection of blood samples at screening, on study, and at end of treatment. Patients without archival tissue also undergo biopsy at screening.

Biological: Pembrolizumab; Procedure: Biospecimen Collection; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: KEYTRUDA

Treatment (cabozantinib, pembrolizumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (cabozantinib, pembrolizumab)

Cabozantinib S-malate DRUG

Given PO

Also known as: Cabometyx, Cometriq

Treatment (cabozantinib, pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (cabozantinib, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, Nuclear Magnetic Resonance Imaging

Treatment (cabozantinib, pembrolizumab)

Eligibility Criteria

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

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.

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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Adrenocortical Carcinoma; Adrenal Cortex Neoplasms

Interventions

pembrolizumab; Specimen Handling; cabozantinib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Shahid S. Ahmed, MBBS

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shahid S. Ahmed, MBBS

CONTACT

404-778-1900; shahid.sattar.ahmed@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 23, 2023
• Study Start: January 15, 2025
• Primary Completion (Estimated): December 16, 2027
• Study Completion (Estimated): December 16, 2028
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (2)