This study has been transitioned to CTIS with ID 2024-518065-10-00 check the CTIS register for the current data. The aim of the study is to demonstrate that HAI P chemotherapy is an effective treatment for unresectable intrahepatic…
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Compare the progression-free survival (PFS) of HAI FUDR/Dex in combination with
systemic GemOx versus systemic GemOx only.
Secondary outcome
1. Compare the overall survival in first-line HAI FUDR/Dex in combination with
GemOx versus systemic GemOx only.
2. Estimate the overall response rate (CR+PR) between treatment groups.
3. Estimate the time to first recurrence patterns between treatment groups.
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.
6. Assess cfDNA and correlate with treatment response and survival outcomes.
7. Assess tumor heterogeneity and correlation with treatment response using
quantitative imaging techniques (radiomics).
8. Assess the correlation between texture features and intratumoral
heterogeneity
Background summary
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver
malignancy after hepatocellular carcinoma and is increasing in incidence. ICC
makes up about 10% of all cholangiocarcinomas. It is an aggressive malignancy
that arises from the epithelium of the biliary tract. ICC is most common in
East Asia, with incidences ranging from 10 to 71 per 100,000 people. An
association has been established with diseases that cause biliary inflammation,
such as primary sclerosing cholangitis. The incidence of ICC in the western
world countries is about 1 per 100,000.
Complete resection remains the only curative option, but is feasible in a
minority of patients (15%). Resection results in a median survival of less than
3 years. However, most patients with ICCs present with an ICC in an advanced
unresectable stage because of the usually clinically silent progression of the
disease. For unresectable ICCs, treatment options are limited. The overall
survival (AO) of a patient with an unresectable ICC is 5 months without
treatment and approximately 1 year with systemic chemotherapy. The 5-year
survival is about 5%. The current treatment regimens used consist of
gemcitabine and cisplatin, which offer minimal AO advantage over gemcitabine
monotherapy (11.7 vs 8.1 months, respectively). Another study found comparable
results of 11.2 and 7.7 respectively (not significant, however due to lack of
power). Previous results are comparable to other gemcitabine-based regimens,
such as gemcitabine and oxaliplatin. A post-hoc analysis of 34 patients with
unresectable
(liver only) ICC treated with gemcitabine and cisplatin showed a 3-year
survival of 0%. More effective therapies are needed to improve survival.
Study objective
This study has been transitioned to CTIS with ID 2024-518065-10-00 check the CTIS register for the current data.
The aim of the study is to demonstrate that HAI P chemotherapy is an effective
treatment for unresectable intrahepatic cholangiocarcinomas.
Study design
Multicenter, prospective randomized controlled phase II trial
Intervention
Chemo pump placement surgery. 2 to 4 weeks later, patients start with 6
consecutive courses (4 weeks per course) of chemotherapy via the pump.
Study burden and risks
Patients will be hospitalized for 4 days to surgically place the pump and to
provide the technetium99-labeled albumin scan. After the operation, 6 cycles of
chemotherapy are administered subcutaneously into pump. This regimen will be
followed in conjunction to the regular chemotherapy. For these 6 cycles 12
outpatient appointments are necessary, which are combined with the regular
appointments for systemic chemotherapy.
York Avenue 1275
New York NY 10065
US
York Avenue 1275
New York NY 10065
US
Listed location countries
Age
Inclusion criteria
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 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
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518065-10-00 |
| EudraCT | EUCTR2022-002851-21-NL |
| ClinicalTrials.gov | NCT04891289 |
| CCMO | NL82386.078.24 |