Trans-arterial treatment of patients with intra-hepatic cholangiocarcinoma not amenable to resection (TOMCAT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Jan 2024 → ongoing

Decision date (initial)

2023-11-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Evaluate the overall survival (OS) of HAI-FUDR/DEX or SIRT in combination with systemic GemOx

Secondary objectives 6

1. Tumour response (CT scans, RECIST 1.1.)
2. Evaluate patient assessed health-related quality-of-life (HR-QoL)
3. Assess the resection rate following downstaging
4. Assess complications, toxicity and side effects in treatment groups
5. Assess ctDNA and correlate with treatment outcomes
6. Collect additional data on the safety of the Tricumed pump in combination with the tapered catheter

Conditions and MedDRA coding

Intra-hepatic cholangiocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Intra-hepatic cholangiocarcinoma. Diagnosis confirmed by biopsy, cytology or previous resection.
2. Not amenable for upfront resection. Defined as: a) A tumour that is technically not resectable with R0 margins (i.e. where resection will not yield an FLR of sufficient size and function) without reconstruction of portal or liver vein, or artery. b) Any multifocality (more than one tumour) irrespective of distance between assumed primary and other lesions. c) Recurrent tumor following resection. d)Radiologically or cytology-proven malignant regional lymph nodes
3. Disease confined to the liver or associated with limited, resectable porta hepatis lymph node metastases.
4. Radiologically measurable disease with at least one lesion > 2 cm in greatest diameter.
5. Physical performance score WHO/ECOG stage 0/1
6. Age > 18 years
7. Assumed ability to tolerate at least one full cycle of systemic chemotherapy (unless no relevant regimen ramains)
8. For eligibility to HAI-FUDR/DEX treatment, patients must be willing and able to go to Oslo every fortnight.
9. Women of childbearing age and potential must be willing to use highly effective contraception during the study and for a period after the study depending on product administered (see section 6.1). Male patients or male patients who have female partners of childbearing age and potential must be willing to use highly effective contraception during the study and for a period after the study depending on product administered (see section 6.1). Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly

Exclusion criteria 16

1. Any non-liver malignant deposit (except for resectable, hilar lymph nodes).
2. Ingrowth into the gallbladder precluding cholecystectomy or fenestration sufficient to prevent any subsequent cholecystitis or necrosis will exclude the patient from HAI, but not from SIRT
3. Ingrowth into any adjacent organ including the diaphragm
4. Serum bilirubin, creatinine or INR outside of normal range
5. Haemoglobin < 7 g/dL and thrombocytes < 75 × 10^9/L
6. Liver failure (if cirrhosis, Child-Pugh B or C for HAI-pump, and above B7 for SIRT)
7. Clinical evidence of portal hypertension (non-surgically related ascites, gastro-oesophageal varices, portal vein thrombosis) will exclude HAI-pump but not SIRT
8. More than 70 % of liver consisting of tumour
9. History of other malignancy past three years except localized/early stage cancer that has been adequately resected
10. Pregnant or lactating women
11. Life expectancy less than three months
12. Externalized biliary duct drain (PTC/PTBD). Stents without externalized component are accepted, also trans-papillary ones
13. Inability to comply with study routines or follow-up procedures
14. Inability to read and comprehend Norwegian
15. Arterial anatomy unsuited for SIRT or HAI, respectively
16. Any reason why, in the view of the investigators, the patient should not be included

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Median survival time

Secondary endpoints 7

1. Proportion of patients surviving 1 year, 2 years
2. Tumour response rate (CT scans, RECIST 1.1) (best response registered at any time): Proportion of patients with Partial Response, proportion of patients with Stable Disease, duration of Stable Disease and proportion of patients converted to resectability following downstaging
3. Change in HR-QoL (EORTC QLQ-C30 and EQ-5D-5L) from baseline to end-of-treatment
4. Change in ctDNA from baseline to end-of-treatment
5. Assess circulating cell-free DNA (ctDNA) before and after treatment and correlate with treatment outcomes
6. Evaluate tumour heterogeneity, based on whole exome sequencing of multiple tumour biopsies obtained at surgery for pump placement or during laparoscopic staging. The genomic findings will be used to stratify patients with respect to response and survival, and will also be used to quantify the degree of tumour heterogeneity.
7. ctDNA and tumour genomic heterogeneity results will be further correlated with texture variables extracted from pre-treatment, contrast-enhanced CT scans.

Investigational products

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

Test 3

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Co-ordinating investigator

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Co-ordinating investigator

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 9 files

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

Application history

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