A randomized trial of systemic chemotherapy with or without hepatic arterial infusion pump chemotherapy for patients with inoperable bile duct cancer in the liver

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Memorial Sloan Kettering Cancer Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518065-10-00

EudraCT number

2022-002851-21

ClinicalTrials.gov

NCT04891289

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Compare the progression-free survival (PFS) of HAI FUDR/Dex in combination with systemic GemOx versus systemic GemOx only.

Secondary objectives 8

1. 1. Compare the overall survival in first-line HAI FUDR/Dex in combination with GemOx versus systemic GemOx only.
2. 2. Estimate the overall response rate (CR+PR) between treatment groups.
3. 3. Estimate the time to first recurrence patterns between treatment groups.
4. 4. Describe the toxicity rates separately for each treatment groups.
5. 5. Define the mutational pattern of IHC and determine the extent to which genomic features and intratumoral heterogeneity correlate with treatment response and survival.
6. 6. Assess cfDNA and correlate with treatment response and survival outcomes.
7. 7. Assess tumor heterogeneity and correlation with treatment response using quantitative imaging techniques (radiomics).
8. 8. Assess the correlation between texture features and intratumoral heterogeneity

Conditions and MedDRA coding

Unresectable intrahepatic cholangiocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Age ≥18 years
2. ECOG 0-1
3. Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (IHC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior XML File Identifier: OlvDuYrPr+P0rcY9vFJaMIbUhz8= Page 23/33 to randomization.
4. Clinical or radiographic evidence of metastatic disease confined to the liver. Note: presence of regional (porta hepatis) lymph node metastases will be allowed, provided they are amenable to resection. (Note: If peritoneal or other extrahepatic disease is found at time of pump placement, the pump will not be implanted. The patient will be removed from study, deemed nonevaluable and will not count toward the overall study accrual.)
5. Radiographically measurable disease. Measurable disease is defined as disease that can be assessed with 2-dimensional measurements on a cross-sectional imaging. Minimum lesion size is 2 cm in greatest diameter as per RECIST criteria
6. Disease must be considered unresectable at the time of preoperative evaluation.
7. Considered candidate for general anesthesia, abdominal exploration and hepatic artery pump placement
8. Patients with chronic hepatitis and/or cirrhosis are eligible, but must be Child-Pugh class A.
9. WBC ≥ 2,000/mcL , ANC ≥ 1000/mcL
10. Platelet count ≥ 75,000/mcL
11. Creatinine ≤ 1.8 mg/dL
12. Total bilirubin < 1.5 mg/dL
13. Hgb > 7 g/dL

Exclusion criteria 13

1. Presence of distant metastatic disease. Patients will undergo radiographic evaluation to exclude the possibility of distant metastatic disease. For patients who have undergone pre- or post-operative biopsies that definitively diagnose IHC, the diagnostic studies may be modified at the discretion of the MSKCC Principal Investigator. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection
2. Patients previously treated with systemic chemotherapy for IHC will be non-eligible.
3. Prior treatment with FUDR.
4. Prior external beam radiation therapy to the liver.
5. Prior ablative therapy to the liver.
6. Diagnosis of sclerosing cholangitis
7. Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis; surgically related ascites does not exclude the patient).
8. Active infection within one week prior to HAI placement.
9. Pregnant or lactating women.
10. History of other malignancy within the past 3 years except with early stage/localized cancer that was surgically resected or radiation treatment that would yield the same result as surgery within the past 3 years.
11. Life expectancy <12 weeks
12. Inability to comply with study and/or follow-up procedures.
13. History of peripheral neuropathy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival

Secondary endpoints 5

1. 1. Compare the overall survival in first-line HAI FUDR/Dex in combination with GemOx versus systemic GemOx only.
2. 2. Estimate the overall response rate (CR+PR) between treatment groups.
3. 3. Estimate the time to first recurrence patterns between treatment groups.
4. 4. Describe the toxicity rates separately for each treatment groups.
5. Define the mutational pattern of IHC and determine the extent to which genomic features and intratumoral heterogeneity correlate with treatment response and survival.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Memorial Sloan Kettering Cancer Center

Sponsor organisation

Memorial Sloan Kettering Cancer Center

Address

1275 York Avenue

City

New York

Postcode

10065-6007

Country

United States

Scientific contact point

Organisation

Memorial Sloan Kettering Cancer Center

Contact name

Andrea Cercek

Public contact point

Organisation

Memorial Sloan Kettering Cancer Center

Contact name

Andrea Cercek

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 7 files

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

Application history

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