Trial Outcomes & Findings for Cabozantinib in Patients With Advanced Hepatocellular Carcinoma With Child Pugh Class B Cirrhosis After First-Line Therapy (NCT NCT04497038)

Last Updated: 2024-08-06

Results Overview

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%.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Up to 29 days after initiating treatment

Results posted on

2024-08-06

Participant Flow

Participant milestones

Participant milestones
Measure	Cabozantinib Cabozantinib 20-60 mg by mouth once daily. Patients received 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.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cabozantinib n=3 Participants Cabozantinib 20-60 mg by mouth once daily. Patients received 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.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=99 Participants
Age, Categorical >=65 years	1 Participants n=99 Participants
Sex: Female, Male Female	0 Participants n=99 Participants
Sex: Female, Male Male	3 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	1 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants
Region of Enrollment United States	3 participants n=99 Participants

PRIMARY outcome

Timeframe: Up to 29 days after initiating treatment

Outcome measures

Outcome measures
Measure	Cabozantinib n=3 Participants Cabozantinib 20-60 mg by mouth once daily. Patients received 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.
Number of DLT Events to Occur	0 Number of DLT events to occur

SECONDARY outcome

Timeframe: 1.7 years

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.

Outcome measures

Outcome measures
Measure	Cabozantinib n=3 Participants Cabozantinib 20-60 mg by mouth once daily. Patients received 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.
Progression-free Survival (PFS)	5.42 Months Interval 4.3 to 5.51

SECONDARY outcome

Timeframe: 1.7 years

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

Outcome measures

Outcome measures
Measure	Cabozantinib n=3 Participants Cabozantinib 20-60 mg by mouth once daily. Patients received 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.
Median Time to Progression (TTP)	5.42 months Interval 4.3 to 5.51

SECONDARY outcome

Timeframe: 1.7 years

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.

Outcome measures

Outcome measures
Measure	Cabozantinib n=3 Participants Cabozantinib 20-60 mg by mouth once daily. Patients received 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.
Overall Survival (OS)	9.33 months Interval 7.91 to 13.4

SECONDARY outcome

Timeframe: 1.7 years

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

Outcome measures

Outcome measures
Measure	Cabozantinib n=3 Participants Cabozantinib 20-60 mg by mouth once daily. Patients received 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.
Overall Response Rate (ORR) (Partial Response + Complete Response)	0 participants with a PR or CR

SECONDARY outcome

Timeframe: Up to 2 months

Population: PK data was never conducted as study was halted prematurely

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

Outcome measures

Outcome data not reported

Adverse Events

Cabozantinib

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Cabozantinib n=3 participants at risk Cabozantinib 20-60 mg by mouth once daily. Patients received 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. Due to low number of enrolled patients, we cannot separate based on dose level in order to maintain confidentiality.
Gastrointestinal disorders Abdominal Pain	33.3% 1/3 • Number of events 1 • 1.7 years
Nervous system disorders Encephalopathy	33.3% 1/3 • Number of events 3 • 1.7 years
Hepatobiliary disorders Hepatic failure	33.3% 1/3 • Number of events 1 • 1.7 years

Other adverse events

Other adverse events
Measure	Cabozantinib n=3 participants at risk Cabozantinib 20-60 mg by mouth once daily. Patients received 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. Due to low number of enrolled patients, we cannot separate based on dose level in order to maintain confidentiality.
Endocrine disorders Hypothyroidism	33.3% 1/3 • Number of events 1 • 1.7 years
Gastrointestinal disorders Abdominal Pain	66.7% 2/3 • Number of events 2 • 1.7 years
Gastrointestinal disorders constipation	66.7% 2/3 • Number of events 2 • 1.7 years
Gastrointestinal disorders diarrhea	66.7% 2/3 • Number of events 5 • 1.7 years
Gastrointestinal disorders Gastroesophageal reflux disease	33.3% 1/3 • Number of events 1 • 1.7 years
Gastrointestinal disorders Periodontal disease	33.3% 1/3 • Number of events 1 • 1.7 years
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • 1.7 years
General disorders fatigue	66.7% 2/3 • Number of events 2 • 1.7 years
Injury, poisoning and procedural complications burn	33.3% 1/3 • Number of events 1 • 1.7 years
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • Number of events 1 • 1.7 years
Musculoskeletal and connective tissue disorders Muscle cramp	66.7% 2/3 • Number of events 2 • 1.7 years
Nervous system disorders Tremor	33.3% 1/3 • Number of events 1 • 1.7 years
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • 1.7 years
Renal and urinary disorders Dysuria	33.3% 1/3 • Number of events 1 • 1.7 years
Respiratory, thoracic and mediastinal disorders Hoarseness	33.3% 1/3 • Number of events 1 • 1.7 years
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	66.7% 2/3 • Number of events 7 • 1.7 years
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Number of events 1 • 1.7 years
Vascular disorders Hypertension	66.7% 2/3 • Number of events 3 • 1.7 years

Additional Information

University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin

University of Michigan Rogel Cancer Center

Phone: 734-936-9499

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place