Phase 1/2 Trial to Evaluate Cabozantinib in Patients With Advanced Hepatocellular Carcinoma With Child Pugh Class B Cirrhosis After First-Line Therapy

University of Michigan Rogel Cancer Center4 sites in 1 country3 target enrollmentAugust 6, 2021

ConditionsAdvanced Adult Hepatocellular Carcinoma

InterventionsCabozantinib

DrugsCabozantinib

Overview

Phase: Phase 1
Intervention: Cabozantinib
Conditions: Advanced Adult Hepatocellular Carcinoma
Sponsor: University of Michigan Rogel Cancer Center
Enrollment: 3
Locations: 4
Primary Endpoint: Number of DLT Events to Occur
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 6, 2021

End Date

May 2, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Michigan Rogel Cancer Center

Responsible Party

Sponsor

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-
•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.

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

Arms & Interventions

Cabozantinib

Cabozantinib 20-60 mg by mouth once daily.

Intervention: Cabozantinib

Outcomes

Primary Outcomes

Number of DLT Events to Occur

Time Frame: Up to 29 days after initiating treatment

MTD/RP2D determined by dose limiting toxicities (DLT) during the first 29 days of therapy. DLTs are outlined in the protocol and assessed per the NCI CTCAE v5.0. The MTD/RP2D will be determined as the dose level with the highest probability of DLT not exceeding 35%.