Clinical Trials /

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

NCT04497038

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2020.007
  • SECONDARY ID: HUM00176488
  • NCT ID: NCT04497038

Conditions

  • Advanced Adult Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
CabozantinibCabozantinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CabozantinibExperimentalCabozantinib 20-60 mg by mouth once daily.
  • Cabozantinib

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D)
Time Frame:Up to 29 days after initiating treatment
Safety Issue:
Description: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%.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:PFS defined as time from date of treatment to date of radiological or clinical progressing (leading to withdrawal from the study), or death from any cause, whichever comes first. PFS will be estimated using the product-limit method of Kaplan and Meier.
Measure:Median time to progression (TTP)
Time Frame:Until date of last disease evaluation (up to 2 years)
Safety Issue:
Description:TTP defined as time from date of treatment to date of radiological or clinical progression (leading to withdrawal from the study).
Measure:Overall survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:Patients will be followed for up to 2 years from treatment discontinuation or until death, whichever comes first, or 3 years after first date of treatment initiation for those that remain on treatment. OS will be estimated using the product-limit method of Kaplan and Meier.
Measure:Overall response rate (ORR) (partial response + complete response)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR (PR + CR) per RECIST v1.1 criteria during active study treatment.
Measure:Pharmacokinetic (PK) profile: Elimination clearance (L/hr)
Time Frame:Up to 2 months
Safety Issue:
Description:Blood draws pre-dose, every 2 weeks until the start of cycle 3

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

July 31, 2020