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Hepatocellular Carcinoma Non-resectablePhase 2CPABNCT06535737

A Phase 2, Single Arm Study of Cabozantinib in Patients With Hepatocellular Carcinoma Who Have Received Prior Atezolizumab and Bevacizumab

A Phase 2 study testing Cabozantinib in people with Hepatocellular Carcinoma Non-resectable, run by Chulalongkorn University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Hepatocellular carcinoma (HCC) is the most common liver cancer and a leading cancer death worldwide. Currently, atezolizumab and bevacizumab combination is the standard of care for patients with advanced HCC. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma Non-resectable
What is being tested?
Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
No sites listed yet
Study dates
Aug 2024to Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Radiological, histological or cytological diagnosis of HCC
  • The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation)
  • Received prior atezolizumab and bevacizumab
  • Progression following atezolizumab and bevacizumab treatment for advanced HCC
  • Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically nonsignificant and/or stable on supportive therapy
  • Age ≥ 18 years old on the day of consent
Show all 23Show fewer
  • ECOG performance status of 0 or 1
  • Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before enrollment:
  • absolute neutrophil count (ANC) ≥ 1200/mm3 (≥ 1.2 x 109/L)
  • platelets ≥ 60,000/mm3 (≥ 60 x 109/L)
  • hemoglobin ≥ 8 g/dL (≥ 80 g/L)
  • Adequate renal function, based upon meeting the following laboratory criteria within 7 days before enrollment:
  • serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation: (140 - age) x weight (kg)/(serum creatinine × 72 [mg/dL]) for males. (For females multiply by 0.85.) AND
  • urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein < 1g
  • Child-Pugh Score of A or B7
  • Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L) within 7 days before enrollment
  • Serum albumin ≥ 2 g/dL (≥ 20 g/L) within 7 days before enrollment
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5.0 upper limit of normal (ULN) within 7 days before enrollment
  • Hemoglobin A1c (HbA1c) ≤ 8% within 7 days before enrollment
  • Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
  • Capable of understanding and complying with the protocol requirements and signed informed consent
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
  • Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression, low body weight, or other reasons.

Who cannot join

  • • Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
  • Receipt of more than one prior systemic therapy for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed.
  • Any type of anticancer agent (including investigational) within 2 weeks before enrollment
  • Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of enrollment. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy.
  • Prior cabozantinib treatment
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before enrollment. Eligible subjects must be without corticosteroid treatment at the time of enrollment.
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  • Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and low-dose LMWH are permitted.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including
  • Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias
  • Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment
  • Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before enrollment
  • Thromboembolic event within 3 months before enrollment. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible
  • o Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
  • Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
  • Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before enrollment, Note: Complete healing of an intra-abdominal abscess must be confirmed prior to enrollment
  • Major surgery within 2 months before enrollment. Complete healing from major surgery must have occurred 1 month before enrollment. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before enrollment. Subjects with clinically relevant complications from prior surgery are not eligible
  • Cavitating pulmonary lesion(s) or endobronchial disease
  • Lesion invading a major blood vessel (eg, pulmonary artery or aorta)
  • Clinically significant bleeding risk including the following within 3 months of enrollment: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors
  • Other clinically significant disorders such as:
  • Active infection requiring systemic treatment, known infection with human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)-related illness
  • Serious non-healing wound/ulcer/bone fracture
  • Malabsorption syndrome
  • Uncompensated/symptomatic hypothyroidism
  • Requirement for hemodialysis or peritoneal dialysis
  • History of solid organ transplantation
  • 9. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry.
  • Moderate or severe ascites
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 7 days before enrollment
  • Note: If the QTcF is > 500 ms in first ECG, a total of 3 ECGs should be performed. If the average of these 3 consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
  • Inability to swallow tablets
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations
  • Pregnant or lactating females
  • Diagnosis of another malignancy within 2 years before enrollment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Suebpong Tanasanvimon, M.D. contact

+666494000 ext. 80648

surbpong@yahoo.com

Nattaya Teeyapan, M.D. contact

+666494000 ext. 80648

nattaya.te@chula.ac.th

About this study

Hepatocellular carcinoma (HCC) is the most common liver cancer and a leading cancer death worldwide. Currently, atezolizumab and bevacizumab combination is the standard of care for patients with advanced HCC. There have not been proven therapy for patients with advanced HCC previously treated with atezolizumab and bevacizumab. Cabozantinib is a proven therapy for patients with advanced HCC previously treated with sorafenib. The study aims to demonstrate the efficacy and safety of cabozantinib in patients with advanced previously treated with atezolziumab and bevacizumab. It is a multi-center single-arm study which all participants will receive cabozantinib. Participants will continue cabozantinib until. disease progression or unacceptable toxicities.

Read the detailed description

Currently, atezolizumab and bevacizumab combination is the standard of care for patients with advanced HCC. There have not been proven therapy for patients with advanced HCC previously treated with atezolizumab and bevacizumab. Cabozantinib is a proven therapy for patients with advanced HCC previously treated with sorafenib. The study aims to demonstrate the efficacy and safety of cabozantinib in patients with advanced previously treated with atezolziumab and bevacizumab.

This is a phase II, single-arm, multi-center trial which all participants will receive cabozantinib. Eligible patients will provide informed consent to participate the trial. The study will enroll 40 patients. All participants will receive cabozantinib until disease progression or unacceptable toxicities. Efficacy assessment will be performed with CT scan or MRI every 8 weeks. Clinical assessments and laboratory tests will be scheduled every 2-4 weeks for safety assessments.

Being tested
Cabozantinib
Keywords
Hepatocellular carcinoma, Cabozantinib
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

Study groups in NCT06535737
Study groupRoleWhat they receive
cabozantinibExperimentalOpen-labelled
Receives: Drug: Cabozantinib

What is being measured

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

  1. Disease control rate (DCR) per RECIST 1.1 at 4th month

    Proportion of participants with stable disease, partial response and complete response at 4th month of cabozantinib treatment based on RECIST 1.1

    Measured: 4th month of treatment

Secondary outcomes (3)

  1. Objective response rate (ORR) per RECIST 1.1 at 4th month

    Proportion of participants with partial response or complete response at 4th month of treatment based on RECIST 1.1

    Measured: 4th month of treatment

  2. Progression-free survival (PFS) per RECIST 1.1

    Time from treatment initiation to documented disease progression per RECIST 1.1 or death

    Measured: Time from treatment initiation to documented disease progression per RECIST 1.1 or death, whichever came first, assessed up to 24 months

  3. Overall survival (OS)

    Time from treatment initiation to patient death

    Measured: Time from treatment initiation to patient death, assessed up to 36 months

Timeline

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

  1. First posted2 Aug 2024
  2. Study startAug 2024 (estimated)
  3. Primary completionJul 2026 (estimated)
  4. Study completionDec 2026 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06535737
Sponsor's protocol ID
onco-059/67
Acronym
CPAB
Status last verified
Jul 2024
First submitted
24 Jul 2024
Last updated
2 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: undecided

Publications

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

    PubMed 18650514

  • Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.

    PubMed 19095497

  • Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

    PubMed 32402160

  • Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, Cicin I, Merle P, Chen Y, Park JW, Blanc JF, Bolondi L, Klumpen HJ, Chan SL, Zagonel V, Pressiani T, Ryu MH, Venook AP, Hessel C, Borgman-Hagey AE, Schwab G, Kelley RK. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018 Jul 5;379(1):54-63. doi: 10.1056/NEJMoa1717002.

    PubMed 29972759

  • Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

    PubMed 29433850

  • Kelley RK, Rimassa L, Cheng AL, Kaseb A, Qin S, Zhu AX, Chan SL, Melkadze T, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Rangel JDG, Ryoo BY, Makharadze T, Merle P, Benzaghou F, Banerjee K, Hazra S, Fawcett J, Yau T. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Aug;23(8):995-1008. doi: 10.1016/S1470-2045(22)00326-6. Epub 2022 Jul 4.

    PubMed 35798016

  • Rumgay H, Arnold M, Ferlay J, Lesi O, Cabasag CJ, Vignat J, Laversanne M, McGlynn KA, Soerjomataram I. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022 Dec;77(6):1598-1606. doi: 10.1016/j.jhep.2022.08.021. Epub 2022 Oct 5.

    PubMed 36208844

  • Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012 Jan 24;12(2):89-103. doi: 10.1038/nrc3205.

    PubMed 22270953

  • Kaposi-Novak P, Lee JS, Gomez-Quiroz L, Coulouarn C, Factor VM, Thorgeirsson SS. Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype. J Clin Invest. 2006 Jun;116(6):1582-95. doi: 10.1172/JCI27236. Epub 2006 May 18.

    PubMed 16710476

  • You H, Ding W, Dang H, Jiang Y, Rountree CB. c-Met represents a potential therapeutic target for personalized treatment in hepatocellular carcinoma. Hepatology. 2011 Sep 2;54(3):879-89. doi: 10.1002/hep.24450. Epub 2011 Jul 19.

    PubMed 21618573

  • Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, Van Vlierberghe H, Trojan J, Kolligs FT, Weiss A, Miles S, Gasbarrini A, Lencioni M, Cicalese L, Sherman M, Gridelli C, Buggisch P, Gerken G, Schmid RM, Boni C, Personeni N, Hassoun Z, Abbadessa G, Schwartz B, Von Roemeling R, Lamar ME, Chen Y, Porta C. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol. 2013 Jan;14(1):55-63. doi: 10.1016/S1470-2045(12)70490-4. Epub 2012 Nov 20.

    PubMed 23182627

  • Greten TF, Korangy F, Manns MP, Malek NP. Molecular therapy for the treatment of hepatocellular carcinoma. Br J Cancer. 2009 Jan 13;100(1):19-23. doi: 10.1038/sj.bjc.6604784. Epub 2008 Nov 18.

    PubMed 19018262

  • You WK, Sennino B, Williamson CW, Falcon B, Hashizume H, Yao LC, Aftab DT, McDonald DM. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res. 2011 Jul 15;71(14):4758-68. doi: 10.1158/0008-5472.CAN-10-2527. Epub 2011 May 25.

    PubMed 21613405

  • Sennino B, Ishiguro-Oonuma T, Wei Y, Naylor RM, Williamson CW, Bhagwandin V, Tabruyn SP, You WK, Chapman HA, Christensen JG, Aftab DT, McDonald DM. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer Discov. 2012 Mar;2(3):270-87. doi: 10.1158/2159-8290.CD-11-0240. Epub 2012 Feb 24.

    PubMed 22585997

  • Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16.

    PubMed 21926191

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Hepatocellular Carcinoma Non-resectable, run by Chulalongkorn University.

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 23 inclusion and 35 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: opening soon, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

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

Contact Suebpong Tanasanvimon, M.D. (+666494000 ext. 80648, surbpong@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease control rate (DCR) per RECIST 1.1 at 4th month (time frame: 4th month of 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 NCT06535737, which also lists 15 linked publications.

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 2 Aug 2024.

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