A Phase I/II Trial of Sapanisertib in Combination With Cabozantinib in β-catenin-mutated Hepatocellular Carcinoma (SAPHIRE)

Status: Recruiting
Location: See all (4) locations...
Intervention Type: Procedure, Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This phase I/II trial studies the side effects and best dose of sapanisertib when given together with cabozantinib, and to see how well they work in treating patients with liver cancer that has spread from where it first started to other places in the body (metastatic) and contains a mutation (change) in the β-catenin gene. Sapanisertib and cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sapanisertib and cabozantinib together may work better than giving cabozantinib alone in treating β-catenin-mutated metastatic hepatocellular carcinoma.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Patients must have histologically or cytologically confirmed HCC, not amenable to curative treatment approach

• For Phase 2, patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam

• For phase 2, patients must have a β-catenin mutation, based on next generation eequencing (NGS) testing through Clinical Laboratory Improvement Amendments (CLIA)-certified commercially available standard of care assay

• Patients must have received at least one prior line of systemic therapy in the metastatic setting, including a prior immune checkpoint inhibitor therapy unless not eligible. For the phase 2 portion, patients must have received at least one and no more than two prior lines of systemic therapy in the metastatic setting, including a prior immune checkpoint inhibitor therapy unless not eligible

• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of sapanisertib in combination with cabozantinib in patients \<18 years of age, children are excluded from this study

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)

• Child Pugh score of A

• Absolute neutrophil count ≥ 1,000/mcL

• Platelets ≥ 30,000/mcL

• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 5 × institutional ULN

• Glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m\^2

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression

• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better

• For the phase 2 portion, availability of archival tumor tissue at the time of patient enrollment for banking for molecular profiling studies

• The effects of sapanisertib and cabozantinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and after completion of drug administration. 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. Both men and women treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and for the following duration after completion of sapanisertib and cabozantinib administration:

‣ 90 days and 120 days after last dose of sapanisertib for women of childbearing potential and men respectively,

⁃ 5 months and 7 months after last dose of cabozantinib for women of childbearing potential and men respectively

• Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Locations
United States
California
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
RECRUITING
Irvine
UC Irvine Health/Chao Family Comprehensive Cancer Center
RECRUITING
Orange
Oregon
Oregon Health and Science University
RECRUITING
Portland
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
RECRUITING
Pittsburgh
Time Frame
Start Date: 2025-11-17
Estimated Completion Date: 2027-08-31
Participants
Target number of participants: 92
Treatments
Experimental: Arm I (Sapanisertib + cabozantinib)
Patients receive sapanisertib PO QD and cabozantinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood collection and imaging scans throughout the study.
Active_comparator: Arm II (Cabozantinib)
Patients receive cabozantinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood collection imaging scans throughout the study.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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