A Phase II Study to Evaluate the Effects of Sequential Therapy With the Anti c-MET/VEGFR Tyrosine Kinase Inhibitor (TKI), Cabozantinib, Followed by an Anti-PD-1 Antibody (Nivolumab) in Patients With Advanced HCC Who Progressed on First-line Therapy

NCT05039736 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0680NCI-2021-09178
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this clinical research study is to learn about the safety and effectiveness of cabozantinib and nivolumab in people with hepatocellular carcinoma (HCC).

Conditions

Hepatocellular Carcinoma; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate overall response rate

  through study completion, an average of 1 year

Study Arms (2)

cabozantinib

EXPERIMENTAL

cabozantinib by mouth every day for 6 weeks

Drug: Cabozantinib

nivolumab

EXPERIMENTAL

nivolumab by vein every 4 weeks for up to 2 years

Drug: Nivolumab

Interventions

Cabozantinib DRUG

Given by PO

Also known as: XL-184, XL184

cabozantinib

Nivolumab DRUG

Given by IV

Also known as: BMS-936558, Opdivo

nivolumab

Eligibility Criteria

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

You may qualify if:

• Is willing and able to provide written informed consent for the trial. Consent for Future Biomedical Research is optional-the subject may participate in the main trial without participating in Future Biomedical Research.
• Has a histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) confirmed by a pathologist at
• Has Barcelona Clinic Liver Cancer (BCLC) Stage-C disease or BCLC Stage-B disease not amenable to locoregional therapy or refractory to locoregional therapy and not amenable to a curative treatment approach (see Appendix 12.8).
• Has a Child-Pugh A liver score within 7 days of first dose of study drug.
• Has documented objective radiographic progression after at least one line of therapy with sorafenib, lenvatinib, bevacizumab, regorafenib, ramucirumab, and immune checkpoint inhibitors including nivolumab, atezolizumab, pembrolizumab, ipilimumab, avelumab, durvalumab, and tremelimumab, or had intolerance to sorafenib, lenvatinib, regorafenib, bevacizumab, or ramucirumab.
• Has measurable disease based on RECIST 1.1 as confirmed by the MD Anderson radiologist.
• Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Patients who have chronic, untreated hepatitis C virus (HCV) are allowed. Has recovered to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Has a performance status of 0 or 1 using the Eastern Cooperative Oncology Group performance status scale within 7 days of first dose of study drug.
• Has adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 7 days before first dose of study treatment
• Has a negative urine or serum pregnancy test (if female) within 72 hours prior to receiving the first dose of study medication (Cycle 1, Day 1) (female subjects of childbearing potential). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception during the course of the study and for 1 year after the last dose of study treatment.
• Acceptable methods of contraception are as follows:
• Single method (one of the following is acceptable):
• intrauterine device (IUD)

You may not qualify if:

• Received prior treatment with cabozantinib.
• Has participated (or is currently participating) in a study of an investigational agent and received (or is receiving) study therapy, herbal/complementary oral or IV medicine including cytotoxic, biologic, or other systemic anticancer therapy, or used (is using) an investigation device, other than sorafenib, lenvatinib, bevacizumab, regorafenib, ramucirumab, and immune checkpoint inhibitors including nivolumab, atezolizumab, pembrolizumab, ipilimumab, avelumab, durvalumab, and tremelimumab, within 4 weeks of the first dose of treatment. Subjects must also have recovered from associated therapy (i.e., to Grade ≤1 or baseline) and from adverse events due to any prior therapy.
• Has developed grade 3 or higher adverse events from prior immune checkpoint inhibitors including nivolumab, atezolizumab, pembrolizumab, ipilimumab, avelumab, durvalumab, and tremelimumab and could not continue the treatment are excluded..
• Had esophageal or gastric variceal bleeding within the last 6 months. All subjects will be screened for esophageal varices, unless such screening has been performed in the past 12 months before first dose of treatment. If varices are present, they should be treated according to institutional standards before starting study treatment.
• Has an ALT \>5x upper limit of normal (ULN) on Day 1 of study treatment.
• Has a total bilirubin \>2.0 mg/dL on Day 1 of study treatment.
• Has clinically apparent ascites or encephalopathy, or untreated varices. Must have undergone an upper endoscopy within 3 months from trial and treated per institutional guidelines for esophageal varices to be eligible.
• Has portal vein HCC invasion at the main portal branch (Vp4) or inferior vena cava, or has cardiac involvement of HCC based on imaging.
• Had encephalopathy in the last 6 months. Subjects on rifaximin or lactulose to control their encephalopathy are not allowed.
• Had a solid organ or hematologic transplant.
• Received radiation therapy for bone metastasis within 2 weeks, and any other radiation therapy within 4 weeks, before first dose of study treatment. Received systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• The use of physiologic doses of corticosteroids may be approved after consultation with BMS/Exelixis or IND Office. -Has received locoregional therapy to liver (TACE, TAE, radiation, radioembolization, or ablation) or surgery to liver or other site within 6 weeks prior to the first dose of study drug.
• Minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7 days prior to the first dose of study treatment (Cycle 1, Day 1). Subjects must have recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to starting therapy.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Exelixis: collaborator

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

cabozantinib; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sunyoung Lee

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 10, 2021
• Study Start: February 24, 2023
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: May 12, 2023

Record last verified: 2023-05