Sapanisertib + Cabozantinib for Liver Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Pregnancy, Allergies, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, sapanisertib and cabozantinib, to determine if they are more effective together than cabozantinib alone in treating liver cancer with a specific gene change called β-catenin mutation. Researchers aim to find the optimal dose and identify any side effects. This trial targets individuals with liver cancer that has spread, possess a β-catenin mutation, and have previously tried at least one unsuccessful treatment. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong CYP3A4-inhibiting agents due to interactions with cabozantinib. It's best to discuss your current medications with the trial team to ensure there are no conflicts.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cabozantinib, when used alone, often causes side effects but has extended patient survival. About 60% of those taking cabozantinib experience side effects, such as diarrhea, tiredness, and loss of appetite.

Studies suggest that combining sapanisertib with cabozantinib could be a promising new treatment. Current research aims to determine how well patients can tolerate this combination. As this trial is in its early stages, it gathers initial safety information, meaning the treatment has only been tested in a small group so far.

In summary, while cabozantinib alone has known side effects, the safety of its combination with sapanisertib remains under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because sapanisertib and cabozantinib together offer a novel approach for liver cancer. Unlike traditional treatments that focus on single targets, this combo acts on both mTOR and MET signaling pathways, potentially enhancing their effectiveness. Sapanisertib inhibits mTOR, a key player in cell growth and survival, while cabozantinib targets MET, which is often linked to cancer spread. This dual-action strategy could provide a more comprehensive attack on the cancer, offering hope for improved outcomes compared to standard therapies like sorafenib or lenvatinib.

What evidence suggests that this trial's treatments could be effective for liver cancer?

This trial will compare the effectiveness of sapanisertib combined with cabozantinib versus cabozantinib alone for treating liver cancer with a β-catenin mutation. Research has shown that using sapanisertib with cabozantinib might be more effective than cabozantinib alone. These drugs block certain proteins that tumors need to grow, which can prevent cancer from spreading. This combination has shown promise in other cancers, such as kidney cancer, suggesting it could be a strong option for liver cancer as well. Cabozantinib alone has an average response time of 8.3 months and a 55.7% response rate, so adding sapanisertib might improve these results. While specific data for liver cancer are still being gathered, the combined approach is believed to enhance treatment effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Anwaar Saeed

Principal Investigator

UPMC Hillman Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with metastatic liver cancer that has a β-catenin gene mutation. They must have tried at least one systemic therapy, be in good physical condition (ECOG ≤ 2), and have proper liver function (Child Pugh score A). Patients should not join if they've had more than two systemic treatments or are too sick to participate.

Inclusion Criteria

My cancer has a β-catenin mutation.

My white blood cell count is healthy.

My bilirubin levels are within normal range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

Dose-escalation study of sapanisertib and cabozantinib to establish the recommended phase 2 dose

28 days per cycle, multiple cycles

Daily oral administration, regular blood collection and imaging scans

Treatment Phase II

Randomized study comparing sapanisertib and cabozantinib combination versus cabozantinib alone

28 days per cycle, multiple cycles

Daily oral administration, regular blood collection and imaging scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Sapanisertib

Trial Overview The SAPHIRE Trial is testing the combination of Sapanisertib and Cabozantinib versus Cabozantinib alone in treating metastatic liver cancer with a specific gene change. It aims to find the best dose and see if this combo is more effective.

How Is the Trial Designed?

Group I: Arm I (Sapanisertib + cabozantinib) Experimental Treatment 4 Interventions

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.

Group II: Arm II (Cabozantinib) Active Control 3 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06811116

Testing the Addition of an Anti-cancer Drug, Sapanisertib ... Giving sapanisertib and cabozantinib together may work better than giving cabozantinib alone in treating β-catenin-mutated metastatic hepatocellular carcinoma.

2. trialx.com trialx.com/clinical-trials/listings/298983/testing-the-addition-of-an-anti-cancer-drug-sapanisertib-to-the-usual-chemotherapy-treatment-cabozantinib-in-metastatic-liver-cell-cancer-with-a-change-in-genes-for-the-protein-catenin-the-saphire-trial/

Testing the Addition of an Anti-cancer Drug, Sapanisertib ... Sapanisertib and cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sapanisertib and cabozantinib ...

3. withpower.com withpower.com/trial/sapanisertib-cabozantinib-for-liver-cancer-fbf41

Sapanisertib + Cabozantinib for Liver Cancer Giving sapanisertib and cabozantinib together may work better than giving cabozantinib alone in treating β-catenin-mutated metastatic hepatocellular carcinoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10722140/

Combining the Tyrosine Kinase Inhibitor Cabozantinib and ... Our findings suggest that cabozantinib plus sapanisertib could be an effective new treatment option for patients with RCC, even those who failed ...

5. oncodaily.com oncodaily.com/drugs/cabozantinib

Cabozantinib: Uses in Cancer, Side effects, Dosage ... 8.3 months, with a response rate of 55.7% for the combination. Common side effects included diarrhea, fatigue, liver toxicity, skin reactions, ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/condition/197/Liver%20Cancer?page=2

Liver Cancer Clinical Research Trials III. To determine the safety and tolerability of the combination of sapanisertib and cabozantinib. IV. To identify molecular subpopulations associated with ...