Cabozantinib treatment for patients with hepatocellular carcinoma (HCC) refractory to previous treatment

Phase 1

Active, not recruiting

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; Hepatocellular carcinoma

• Registration Number: EUCTR2019-004126-13-DE
• Lead Sponsor: niversity Leipzig

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-06-04
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Patients with diagnosis of locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC)
2. 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)
3. Disease progression or end of therapy due to toxicity during/after pre-therapy
4. CTCAE = Grade 2 prior to study registration, with the exception of alopecia
5. ECOG (Eastern Cooperative of Onco-logy Group) Index 0 or 1
6. Age = 18 years
7. Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion Criteria

1. Significant portal hypertension (moderate or severe ascites)
2. No adequate controlled arterial hypertension (RR > 140/80mmHg)
3. ALAT/ASAT five times higher then upper normal value
4. Hepatic encephalopathy (every stage)
5. Liver cirrhosis Child-Pugh B or C
6. Known fibrolamellar HCC, sarcomatoid HCC, or cholangiocarcinoma mixed with HCC
7. 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
8. Severe infection with alteration of general condition within four weeks prior to initiation of study treatment
9. Severely impaired kidney function (CKD: stadium 4: GFR<30)
10. Myocardial infarction within 12 months prior to initiation of study treatment
11. Epilepsy
12. Heart failure, Cardiac arrhythmia, respectively long-QT syndrome
13. 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)
14. Chronic inflammatory bowel disease (e.g. colitis ulcerosa, diverticulitis, Crohn’s disease)
15. Increased risk of thromboembolism due to medical history or disease
16. Significant alcohol consumption (>1 drink/day; 1 drink=0.25l beer or 0,1l wine or 2cl spirituous beverages)
17. Known active HIV infection
18. Known hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption
19. Prior Cabozantinib use
20. Concomitant anticoagulation, at therapeutic doses*
21. Predicted life expectancy of less than 6 months
22. Female patients who do not meet at least one of the following criteria:
• Postmenopausal women (Appendix 18.1) (for at least 1 year before the screening visit) OR
• Postoperative status (6 weeks after bilateral ovariectomy with or without hysterectomy) OR
• If they are of childbearing potential, agree to practice one highly effective method of contraception and one additional effective (barrier) method at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.) OR
• Abstinence OR
• Vasectomy of the partner
23. Male patients not using one of the following variants for contraception including a period of 4 months after the completion of the therapy:
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. OR
• Condition after vasectomy OR
• Condom
24. Participation in any other interventional trials within 28 days prior to initiation of study treatment
25. Suspected lack of compliance to previous treatments; inability to take the medication
26. Pregnancy or lactation, or intention of becoming pregnant during study treatment
* Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (= 1 mg/day), and low-dose LMWH are permitted.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess feasibility, safety and efficacy signals of Cabozantinib in patients with prior non-response or disease progression during a PD-1 or PD-L1 inhibitor treatment.;Secondary Objective: 1. Survival and response:<br>a) Overall survival (OS)<br>b) Progression-free survival (PFS)<br>c) Duration of response (DoR)<br>d) Response rates including ORR<br>2. Feasibility <br>e) Median average dose<br>3. Image-based endpoints<br>f) Tumor progression<br>g) Progression of tumoral macrovascular invasion<br>h) Progression of extrahepatic HCC manifestations<br>i) Total tumor volume<br>j) Affection rate<br>4. Biomarkers and health status<br>k) Concentration of Alpha-fetoprotein<br>l) Child-Pugh classification score<br>m) ECOG Performance status<br>5. Safety;Primary end point(s): Time on treatment (TT) for patients with HCC who have shown disease progression during treatment with a PD-1 or PD-L1 inhibitor;Timepoint(s) of evaluation of this end point: At end of treatment or end of study, respectively.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Survival and response:<br>a) Overall survival (OS)<br>b) Progression-free survival (PFS)<br>c) Duration of response (DoR)<br>d) Response rates including ORR<br><br>2. Feasibility <br>e) Median average dose<br><br>3. Image-based endpoints<br>f) Tumor progression<br>g) Progression of tumoral macrovascular invasion<br>h) Progression of extrahepatic HCC manifestations<br>i) Total tumor volume (TTV)<br>j) Affection rate<br><br>4. Biomarkers and health status<br>k) Concentration of Alpha-fetoprotein<br>l) Child-Pugh classification score<br>m) ECOG Performance status<br><br>5. Safety (descriptive documentation);Timepoint(s) of evaluation of this end point: Secondary endpoints (survival, response, feasibility): at end of treatment, documented tumor progression, death, or end of study, respectively.<br>Secondary endpoints (image-based endpoints, biomarkers, health status): at visits at 3, 6, 9 and 12 months after registration, and end-of-treatment-visit (if applicable).