Cabozantinib Treatment in a Phase II Study for Patients With Hepatocellular Carcinoma (HCC) Refractory to PD-1 Inhibitors

NCT04767906 | Completed Phase 2 DMC

• 1 other identifier: CaPture
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 5

Brief Summary

The CaPture trial is a prospective, multi-centre, non-randomized phase II study. Its aim is to assess feasibility, safety and efficacy signals of Cabozantinib treatment in patients with HCC and prior non-response or disease progression during a PD-1 or PD-L1 inhibitor treatment. Since the potential study population is very small, the sample size has been fixed in advance to N = 40. Time on treatment (TT) will be measured as primary endpoint.

Conditions

Hepatocellular Carcinoma

Keywords

HCC, Cabozantinib, PD-1 inhibitor, PD-L1 inhibitor

Outcome Measures

Primary Outcomes (1)

• time on treatment (TT)

  Primary endpoint of the trial is the time on treatment (TT). TT is defined as one plus the last date of treatment with Cabozantinib minus the first date of treatment with Cabozantinib, and will be measured in days (note that Cabozantinib will be administered as a single dose per day). The end of treatment must be confirmed by the investigator. In particular, planned discontinuations or missing compliance will not be considered as end of treatment without confirmation.

  start of treatment until end of treatment (max. 336 days)

Secondary Outcomes (15)

• Overall survival (OS)

  screening visit until date of death, maximum until the last registered patient reached the second follow-up (6 months after end of therapy)

• Progression-free survival (PFS)

  screening visit until the time to tumor progression or date of death from any cause, whichever came first, maximum until the last registered patient reached the second follow-up (6 months after end of therapy)

• Duration of response (DoR)

  screening visit until the time from achievement of response or date of death from any cause, whichever came first, maximum until the last registered patient reached the second follow-up (6 months after end of therapy)

• Response rates

  screening visit until end of treatment (max. 336 days)

• Median average dose

  start of treatment until end of treatment (max. 336 days)

Study Arms (1)

Cabozantinib

OTHER

Enrolled patients start with 60mg of Cabozantinib. The maximum duration of treatment is 336 days. The dose can be adjusted by the physician to 40mg or 20mg.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

The medication is taken once a day for 336 days (max.). The start dose is 60mg and can be reduced according to the physicians decision. 40mg and 20mg are also available.

Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Patients with diagnosis of locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC)
• Pre-Treatment with a PD-1/PD-L1 inhibitor for at least one administration which was given as first line or as following line systemic treatment alone or in combination with other systemic or local treatments (e.g. TACE)
• Disease progression or end of therapy due to toxicity during/after pre-therapy
• CTCAE ≤ Grade 2 prior to study registration, with the exception of alopecia
• ECOG (Eastern Cooperative of Onco-logy Group) Index 0 or 1
• Age ≥ 18 years
• Written informed consent

You may not qualify if:

• Significant portal hypertension (moderate or severe ascites)
• No adequate controlled arterial hypertension (RR \> 140/80mmHg)
• ALAT/ASAT five times higher then upper normal value
• Hepatic encephalopathy (every stage)
• Liver cirrhosis Child-Pugh B and C
• Known fibrolamellar HCC, sarcomatoid HCC, or cholangiocarcinoma mixed with HCC
• Major surgical procedure, other than for diagnosis, within eight weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Severe infection with alteration of general condition within four weeks prior to initiation of study treatment
• Severely impaired kidney function (CDK: stadium 4: GFR\<30)
• Myocardial infarction within 12 months prior to initiation of study treatment
• Epilepsy
• Heart failure, Cardiac arrhythmia, respectively long-QT syndrome
• Severe bleeding or high risk for the development of severe bleeding, including esophageal varices \> 1° or esophageal varices with red marks as seen on a lighted stomach scope (endoscopy)
• Chronic inflammatory bowel disease (e.g. colitis ulcerosa, diverticulitis, Crohn's disease)
• Increased risk of thromboembolism due to medical history or disease

Sponsors & Collaborators

• University of Leipzig: lead

Study Sites (5)

Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus Medizinische Klinik und Poliklinik I

Dresden, Saxony, 01307, Germany

Location

MVZ Mitte/MVZ Delitzsch GmbH

Leipzig, Saxony, 04103, Germany

Location

University Hospital Leipzig

Leipzig, Saxony, 04103, Germany

Location

Charite Universitätsmedizin, Campus Virchow Klinikum, Klinik für Hepatologie/Gastroenterologie

Berlin, 13353, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

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

• Florian van Bömmel, MD

  Authorised representative of the sponsor (University of Leipzig)

  STUDY CHAIR

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: Patients with hepatocellular carcinoma with prior non-response or disease progression during a PD-1 or PD-L1 inhibitor treatment will be treated with Cabozantinib.

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: February 23, 2021
• Study Start: December 14, 2021
• Primary Completion: July 19, 2024
• Study Completion: July 19, 2024
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: After publication of the major results.
• Access Criteria: Individual patient data underlying published results will be shared after re-identification. This requires approval by the local Institutional Review Board (IRB) of the researcher requesting the data along with public registration of the meta-analysis.

Locations

DE (5)