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Advanced Adult Hepatocellular CarcinomaPhase 1/2NCT04497038

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

A Phase 1/2 study testing Cabozantinib in people with Advanced Adult Hepatocellular Carcinoma, run by University of Michigan Rogel Cancer Center at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Adult Hepatocellular Carcinoma
What is being tested?
Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
4 sitesUnited States
Study dates
6 Aug 2021to 2 May 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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:
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  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

Other trials in United States

About this study

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

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.

Being tested
Cabozantinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    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.

Study groups in NCT04497038
Study groupRoleWhat they receive
CabozantinibExperimentalCabozantinib 20-60 mg by mouth once daily.
Receives: Drug: Cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of DLT Events to Occur

    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%.

    Measured: Up to 29 days after initiating treatment

Secondary outcomes (5)

  1. Progression-free Survival (PFS)

    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.

    Measured: 1.7 years

  2. Median Time to Progression (TTP)

    TTP defined as time from date of treatment to date of radiological or clinical progression (leading to withdrawal from the study).

    Measured: 1.7 years

  3. Overall Survival (OS)

    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.

    Measured: 1.7 years

  4. Overall Response Rate (ORR) (Partial Response + Complete Response)

    ORR (PR + CR) per RECIST v1.1 criteria during active study treatment.

    Measured: 1.7 years

  5. Pharmacokinetic (PK) Profile: Elimination Clearance (L/hr)

    Blood draws pre-dose, every 2 weeks until the start of cycle 3

    Measured: Up to 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2020
  2. Study start6 Aug 2021
  3. Primary completion2 May 2023
  4. Study completion2 May 2023

Why it stopped: loss of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04497038
Sponsor's protocol ID
UMCC 2020.007
Other IDs
HUM00176488
Status last verified
Jul 2024
First submitted
29 Jun 2020
Last updated
6 Aug 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cabozantinib in people with Advanced Adult Hepatocellular Carcinoma, run by University of Michigan Rogel Cancer Center at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of DLT Events to Occur (time frame: Up to 29 days after initiating treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04497038.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.

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