Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV
Pilot Trial of Nivolumab Plus Cabozantinib for Advanced Solid Tumors in Patients With HIV Infection
3 other identifiers
interventional
8
1 country
3
Brief Summary
This phase I trial investigates the side effects of cabozantinib and nivolumab in treating patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and who are undergoing treatment for human immunodeficiency virus (HIV). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and nivolumab may shrink or stabilize cancer in patients undergoing treatment for HIV.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2021
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 14, 2020
CompletedFirst Posted
Study publicly available on registry
August 17, 2020
CompletedStudy Start
First participant enrolled
November 22, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 11, 2024
CompletedResults Posted
Study results publicly available
May 28, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
February 6, 2027
ExpectedMay 28, 2026
May 1, 2026
3 years
August 14, 2020
April 7, 2026
May 8, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of Dose Limiting Toxicities (DLTs)
Dose-limiting toxicity (DLT) were defined as any treatment-related grade 3 or 4 nonhematologic toxicity during the first cycle of therapy, including grade 3 nausea and/or vomiting and grade 3 diarrhea despite prophylaxis and/or treatment or any of the following grade 4 hematologic toxicities during the first cycle of therapy: thrombocytopenia and neutropenia of more than 7 days duration, neutropenia of any duration with fever or documented infection; additionally, treatment delay of 14 days or greater during Cycle 1 due to unresolved toxicity will be considered a DLT.
28 days
Secondary Outcomes (31)
Objective Response Rate (ORR)
Up to 24 months
Best Overall Response
Up to 24 months
Best Overall Response (Off Treatment)
Up to 24 months
12-month Progression-free Survival (PFS)
At 12 months (from start of treatment)
24-month Progression-free Survival (PFS)
At 24 months (from start of treatment)
- +26 more secondary outcomes
Other Outcomes (4)
Change in Serum Markers of Immune Activation
Baseline up to 16 weeks post treatment
Change in Immune Checkpoint Markers
Baseline up to 16 weeks post treatment
Change in Angiogenesis Markers
Baseline up to 16 weeks post treatment
- +1 more other outcomes
Study Arms (1)
Treatment (cabozantinib s-malate, nivolumab)
EXPERIMENTALPatients receive cabozantinib s-malate PO QD on days 1-28 of each cycle and nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 1 year or 1 year after a partial response is achieved, or 6 months after a complete response is achieved in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT scan and/or MRI as well as blood sample collection throughout the trial.
Interventions
Undergo blood sample collection
Given PO
Undergo CT
Undergo MRI
Given IV
Eligibility Criteria
You may qualify if:
- Age \>= 18 years. Children are excluded from this study, but will be eligible for future pediatric trials
- For the six-patient safety cohort, subjects must have histologically or cytologically confirmed advanced solid tumors that are metastatic or recurrent, and require palliative systemic treatment, for which there are either Food and Drug Administration (FDA) approved indications for XL184 (cabozantinib) or nivolumab or have at least phase 2 data clearly indicating activity (such as renal cell carcinoma \[RCC\], hepatocellular carcinoma \[HCC\], medullary thyroid carcinoma \[MTC\], melanoma, non-small cell lung cancer \[NSCLC\], head and neck cancer, urothelial carcinoma, small cell lung cancer \[SCLC\], radioiodine-refractory differentiated thyroid cancer, ovarian cancer, castration-resistant prostate carcinoma \[CRPC\], and triple-negative breast cancer \[TNBC\]). Subjects must have progressed, or are intolerant, or decline systemic therapy associated with clinically significant survival benefit if checkpoint blockade is not an approved or accepted treatment. The expansion cohort is limited to subjects with KS. Histologic, cytologic, and pathologic confirmation of KS is required
- Any number of prior cancer therapies will be permitted, including treatment naive subjects. (Note: For KS, treatment naive asymptomatic subjects will be permitted. But treatment naive KS subjects with visceral symptomatic disease or complicated KS HHV 8 disease including Castleman's disease will be excluded and should receive front-line standard of care)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky \>= 80%)
- Subjects with tumors other than KS must have evaluable disease
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 75,000/mcL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (If, however, the participant has Gilbert's disease or unconjugated hyperbilirubinemia that is considered to be secondary to antiretroviral therapy, then the total bilirubin must be =\< 3 x ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
- Creatinine =\< 1.5 institutional ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula)
- Hemoglobin \>= 9 g/dL
- CD4 count \>= 50/mcL
- Subjects must have known HIV infection as below: Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive Western blot, or any other federally approved licensed HIV test. Alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and Western blot, or other approved diagnostic tests. Subjects must receive appropriate care and treatment for HIV infection. An eligible patient should be on anti-retroviral therapy (ART) that is not strongly CYP3A4 inhibiting or otherwise prohibited by the protocol (e.g. drug-drug interactions) or the patient must be converted to one of these regimens before starting investigational therapy in order to avoid dose modulation of cabozantinib
- Life expectancy of \>= 12 weeks
- For subjects with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- +5 more criteria
You may not qualify if:
- For the safety run-in cohort, subjects who have received prior XL184 (cabozantinib), PD-1/PD-L1 inhibitor, or VEGFR inhibitor are ineligible. Prior treatment with these agents is allowed for the expansion KS cohort
- Subjects on potent CYP3A4-inhibiting agents are ineligible, such as:
- Antiretroviral: ritonavir, cobicistat, indinavir, atazanavir, delavirdine
- Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin
- Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole, posaconazole
- Antidepressants: nefazodone
- Antidiuretic: conivaptan
- Gastrointestinal (GI): cimetidine, aprepitant
- Hepatitis C: boceprevir, telaprevir
- Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or pummelos, star fruit, exotic citrus fruits, or grapefruit hybrids Of note, to meet the eligibility requirement, subjects are allowed to convert their antiretroviral medications to one of the regimens not including potent CYP3A4-inhibiting agents, when the subjects have progressed, are intolerant, or decline the standard systemic therapy for their advanced tumors.
- Subjects must receive appropriate care and treatment for HIV infection, including antiretroviral medications, when clinically indicated (including no ART) and should be under the care of a physician experienced in HIV management. Subjects will be eligible provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 8 weeks following study entry.
- To enroll in the study, the participants should be on the protocol accepted ART as long as they are receiving XL184 (cabozantinib)
- Subjects who have had cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment, or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier
- The subject has received radiation therapy:
- To the thoracic cavity, abdomen, or pelvis within 4 weeks before the first dose of study treatment, or has ongoing complications, or is without complete recovery and healing from prior radiation therapy
- +45 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
Northwestern University
Chicago, Illinois, 60611, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Haiying Cheng, MD - Associate Professor, Department of Oncology
- Organization
- Albert Einstein College of Medicine, Montefiore Einstein Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Haiying Cheng
Albert Einstein College of Medicine EDDOP
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 14, 2020
First Posted
August 17, 2020
Study Start
November 22, 2021
Primary Completion
November 11, 2024
Study Completion (Estimated)
February 6, 2027
Last Updated
May 28, 2026
Results First Posted
May 28, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.