Phase II Open Label, Single-Arm Study of Cabozantinib in Combination With Pembrolizumab in the Treatment of Locally Advanced or Metastatic Adrenocortical Carcinoma
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.
• 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
• The effects of study drugs on the developing human fetus are unknown. For this reason, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
• Female of child-bearing potential (FCBP) and men treated or enrolled on this protocol must agree to use adequate contraception with a failure rate \< 1% prior to study entry, for the duration of study participation, and 5 months after completion of study drug administration.
‣ Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices
⁃ The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence e.g., calendar, ovulation, symptothermal, or postovulation methods and withdrawal are not adequate methods of contraception
⁃ Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating \[FSH\] level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site
• Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation