Efficacy and Safety of Cabozantinib in Patients With Hepatocellular Carcinoma

NCT04435977 | Unknown Phase 2

• 1 other identifier: ONC-2019-002
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-center, Phase II trial designed to estimate in terms of PFS the efficacy of cabozantinib, given as second- or third- line treatment in HCC patients that progress on or are intolerant to immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 antibodies.

Conditions

Hepatocarcinoma

Outcome Measures

Primary Outcomes (1)

• PFS

  PFS on cabozantinib treatment (considering as PFS events: clinical or radiological progressive disease, per RECIST 1.1, or death).

  through study completion, an average of 1 year

Secondary Outcomes (2)

• ORR

  through study completion, an average of 1 year

• safety and tolerability

  through study completion, an average of 1 year

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Drug: Cabozantinib Subjects who meet all study eligibility criteria will take tablets containing 60 mg of cabozantinib once daily orally. Required dose reductions will be in decrements of 20 mg cabozantinib (maximum two dose reductions).

Drug: Cabozantinib 60 MG

Interventions

Cabozantinib 60 MG DRUG

• The assigned dose for study treatment is 60 mg qd. Two dose reductions will be permitted (Table 2): * 60 mg qd to 40 mg qd (level 1) * 40 mg qd to 20 mg qd (level 2)

Cabozantinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted)
• A baseline tumor tissue (newly obtained) available at screening is optional. Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines and requirements for such procedure. Biopsy cannot be performed less than ten days before treatment start.
• The subject has disease that is not amenable to a locoregional treatment approach (eg, transplant, surgery, radiofrequency ablation, TACE)
• Patients must have documented disease progression following at least 1 and no more than 2 prior systemic regimens for advanced disease (nonresectable or metastatic), the last of which includes immune checkpoint inhibitors. Alternatively, eligible patients may have experienced an immune-related, requiring treatment discontinuation.
• Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically not significant and/or stable on supportive therapy
• Age ≥ 18 years old on the day of consent
• ECOG performance status of 0 or 1 (See Appendix V)
• Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before treatment beginning:
• a. absolute neutrophil count (ANC) ≥ 1200/mm3 (≥ 1.2 x 109/L)
• b. platelets ≥ 60,000/mm3 (≥ 60 x 109/L)
• c. hemoglobin ≥ 8 g/dL (≥ 80 g/L)
• Adequate renal function, based upon meeting the following laboratory criteria: 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)
• Child-Pugh Score of A (See Appendix IV)
• Total bilirubin ≤ 2 mg/dL within 7 days before treatment start
• Serum albumin ≥ 2.8 g/dL (≥ 28 g/L) within 7 days before treatment start

You may not qualify if:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
• Child-Pugh score of B or C
• Any type of anticancer agent (including investigational) within 2 weeks before treatment start
• 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 treatment start. 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 treatment start. Eligible subjects must be without corticosteroid treatment at the time of treatment start
• 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:
• a. Cardiovascular disorders including:
• i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias
• ii. Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic, or \> 100 mm Hg diastolic despite optimal antihypertensive treatment
• iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before treatment start.
• iv. Thromboembolic event within 3 months before treatment start. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible
• b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Lorenza Rimassa, MD

  Istituto Clinico Humanitas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenza Rimassa, MD

CONTACT

02 8224; lorenza.rimassa@humanitas.it

Nicola Personeni, MD

CONTACT

02 8224; nicola.personeni@humanitas.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single group assignement

Study Record Dates

• First Submitted: June 12, 2020
• First Posted: June 17, 2020
• Study Start: January 30, 2020
• Primary Completion: June 1, 2023
• Study Completion: September 1, 2023
• Last Updated: June 17, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)