Cabozantinib in Patients With Advanced Hepatocellular Carcinoma With Child Pugh Class B Cirrhosis After First-Line Therapy

NCT ID: NCT04497038

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-06
• Study Completion Date: 2023-05-02

Brief Summary

The aim of this study is to determine the safety and efficacy of cabozantinib in the management of unresectable or metastatic hepatocellular carcinoma (HCC) with underlying Child-Pugh class B cirrhosis.

Conditions

Advanced Adult Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cabozantinib

Cabozantinib 20-60 mg by mouth once daily.

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Patients will receive therapy with cabozantinib. Dosage in the trial will start at 40 mg PO daily. Each patient will be assessed for the development of toxicity according to the NCI Common Terminology Criteria for Adverse Events, version 5.0. Dose adjustments may be made per the Time-To-Event modification of the Continual Reassessment Method (TITE-CRM). The maximum dosage will be 60 mg PO daily and the minimum will be 20 mg PO daily.

Interventions

Cabozantinib

Patients will receive therapy with cabozantinib. Dosage in the trial will start at 40 mg PO daily. Each patient will be assessed for the development of toxicity according to the NCI Common Terminology Criteria for Adverse Events, version 5.0. Dose adjustments may be made per the Time-To-Event modification of the Continual Reassessment Method (TITE-CRM). The maximum dosage will be 60 mg PO daily and the minimum will be 20 mg PO daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must have a radiologically consistent (early enhancement and delayed enhancement washout) or pathologically confirmed diagnosis of hepatocellular carcinoma that is not eligible for curative resection, transplantation, or ablative therapies.
• Prior radiation, liver directed therapy (including bland, chemo- or radioembolization, or ablation), or hepatic resection are permitted if ≥4 weeks from start of therapy. Extra-hepatic palliative radiation is permitted if completed ≥2 weeks prior to first dose of study therapy and the patient has recovered to ≤ grade 1 toxicity.
• Patients must have radiographically measurable disease (RECIST1.1) in at least one site not previously treated or with progression after radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic site.
• Patients must have either progressed or deemed intolerant of first-line systemic therapy. More than one line of systemic therapy is not permitted. The last dose should be at least 2 weeks from first dose of study therapy. Prior treatment may not contain cabozantinib.
• Recovery to ≤ grade 1 from toxicities related to any prior treatments, unless the AEs were clinically non-significant and/or stable on supportive therapy
• Must have a Child-Pugh score of B7 or B8
• Must have an ECOG performance status of 0-1.
• Ability to understand and willingness to sign IRB-approved informed consent.
• Willing to provide archived tissue, if available, from a previous diagnostic biopsy.
• Must be able to tolerate CT and/or MRI with contrast.
• Adequate organ function obtained ≤ 2 weeks prior to enrollment.

Exclusion Criteria

• Must not have uncontrolled ascites (requiring paracentesis within 3 months of screening) or hepatic encephalopathy requiring hospitalization (within 6 months of screening)
• Must not have prior history of organ transplantation.
• No known brain metastasis unless adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before registration. Eligible subjects must have been without corticosteroid treatment at the time of registration.
• Must not have undergone a major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (e.g., simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
• Must not have an active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ. Patients with history of malignancy are eligible provided primary treatment of that cancer was completed > 1 year prior to enrollment and the patient is free of clinical or radiologic evidence of recurrent or progressive malignancy.
• Must not have uncontrolled, significant intercurrent or recent illness including, but not limited to the following conditions:

• Cardiovascular disorders (Congestive heart failure or uncontrolled hypertension; or stroke, myocardial infarction, or other ischemic or thromboembolic event within 6 months before first dose)
• Gastrointestinal disorders, including those associated with a high risk of perforation or fistula formation
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon of red blood or other history of significant bleeding within 12 weeks before first dose
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
• Lesions invading or encasing any major blood vessels except thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor
• Other clinically significant disorders that would preclude safe study participation (serious non-healing wound/ulcer/bone fracture; uncompensated/symptomatic hypothyroidism; known HIV)
• Must not have untreated or incompletely treated varices with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (in accordance with institutional standards) without any episodes of recurrent overt GI bleeding requiring transfusion or hospitalization for at least 6 months prior to study entry are eligible
• Must not have a psychiatric illness, other significant medical illness, or social situation (such as involuntary incarceration) which, in the investigator's opinion, would limit compliance or ability to comply with study requirements
• Women must not be pregnant or breastfeeding since cabozantinib may harm the fetus or child.
• Women of child-bearing potential (not surgically sterilized and between menarche and 1-year post menopause) and men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) OR abstinence prior to study entry, for the duration of study participation, and for 4 months following completion of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Prisoners or subjects who are involuntarily incarcerated, or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness would be excluded.
• Concomitant treatment with strong inducers or inhibitors of CYP3A4 is not allowed. Patients must discontinue the drug(s) at least 14 days prior to first study dose on the study.
• Concomitant anticoagulation with oral anticoagulants (e.g. warfarin, direct thrombin and factor Xa inhibitors), or platelet inhibitors (e.g. clopidogrel) is not allowed.
• Must not have corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exelixis

INDUSTRY

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vaibhav Sahai, MBBS, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

Northwestern University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HUM00176488

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2020.007

Identifier Type: -

Identifier Source: org_study_id