Study on the effect of 2 immunotherapy drugs in combination with radioactive glass spheres on the survival in liver cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum der Universitaet Muenchen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Dec 2023 → ongoing

Decision date (initial)

2024-08-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Boston Scientific · AstraZeneca

External identifiers

EU CT number

2024-515127-11-00

EudraCT number

2020-003925-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To assess the objective response rate in non-resectable HCC patients employing a treatment strategy with first-line systemic treatment in combination with personalized SIRT compared to standard SIRT (historical control)

Secondary objectives 2

1. To evaluate the safety and quality of life of treatment with durvalumab/tremelimumab in combination with SIRT
2. To evaluate Overall Survival, progression-free survival, time to progression, and disease control rate of patients treated with durvalumab/tremelimumab in combination with SIRT

Conditions and MedDRA coding

hepatocellular carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histological diagnosis of HCC
2. Life expectancy of at least 12 weeks
3. Disease which is not amenable to curative surgical or ablation treatment but eligible for locoregional treatment including portal vein invasion Vp1-3. Patients who are candidates for liver transplantation list are eligible at the discretion of the local investigator.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Preserved liver function, as defined by a Child-Pugh score A and B7

Exclusion criteria 9

1. Diffuse HCC or presence of vascular invasion in the portal vein main stem (Vp4) or extrahepatic spread (including extrahepatic lymph node affection or metastasis) or more than 7 lesions or at least one lesion ≥ 10 cm
2. Major gastrointestinal bleeding within 4 weeks prior to inclusion
3. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
4. Decompensated liver function as defined by any of the following: Clinically meaningful ascites, hepatic encephalopathy or history of hepatic encephalopathy, Child Pugh ≥8 points. The presence of clinically meaningful ascites is defined as any ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. Subjects on stable doses of diuretics for ascites for ≥2 months are eligible.
5. Uncontrolled pleural effusion or pericardial effusion
6. Co-infection of HBV and HCV. Patients with a history of HCV infection but who are negative for HCV RNA by polymerase chain reaction (PCR) will be considered non-infected with HCV.
7. Prior systemic therapy for HCC (including previous CPI or VEGFi treatment)
8. Prior treatment with TACE or SIRT if active tumor recurrence is located in previously treated hepatic segment or recurrence within ≤ 6 months after prior TACE or SIRT
9. Ineligibility for locoregional treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR compared to SIRT historical control)

Secondary endpoints 9

1. Overall survival (OS)
2. Progression-free survival (PFS)
3. Complete response rate (CRR)
4. Disease control rate (DCR)
5. Duration of response (DoR)
6. Time to deterioration of liver function, defined as time from randomization to worsening of CTCAE grade compared with baseline and persisting for ≥30 days for any of these parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, and international normalized ratio (INR); separately for patients in Arm A and Arm B
7. Time to locally/locoregional untreatable progression (TTuP), defined as time from randomization to occurrence of any of the following conditions: progression which would require targeting of more than 3 pretreated lesions as determined by the latest staging investigation, progression occurring due to diffuse tumor growth, occurrence of vascular invasion, occurrence of extrahepatic spread, worsening of liver function to Child-Pugh score 8 or higher
8. Time to stage progression (defined as time from randomization to disease progression to BCLC C)
9. To assess the quality of life (QoL), as determined by the EORTC QLQ-C30 and EORTC QLQ-HCC18 questionnaires.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum der Universitaet Muenchen AöR

Sponsor organisation

Klinikum der Universitaet Muenchen AöR

Address

Marchioninistrasse 15, Hadern Hadern

City

Munich

Postcode

81377

Country

Germany

Scientific contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

Prof. Dr. med. Max Seidensticker

Public contact point

Organisation

Klinikum der Universitaet Muenchen AöR

Contact name

Prof. Dr. med. Max Seidensticker

Third parties 1

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications