Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma

NCT ID: NCT02773485

Last Updated: 2022-10-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2025-06-30

Brief Summary

The study evaluates impact of high dose radiation on overall survival in patients with unresectable nonmetastatic cholangiocarcinoma. The study randomizes patient between systemic chemotherapy alone and systemic chemotherapy and high dose radiation

Detailed Description

Currently the standard of care of unresectable non-metastatic cholangiocarcinoma is chemotherapy which has a median survival of 11.7 months (ABC-02 study). While this study included almost 60% of patients with cholangiocarcinomas (intrahepatic, extra hepatic and hilar), almost 73-76% of patients in each arm had metastases to begin with. And while the overall survival of the entire cohort was significantly improved by gemcitabine plus cisplatin compared to cisplatin alone, the hazard ratios for intrahepatic {0.57 (0.34-0.94)}, extra hepatic {0.73 (0.43-1.23)} and hilar cholangiocarcinomas {0.59 (0.32-1.09)} were all insignificant. Even though concurrent chemoradiation+/= brachytherapy has been used for management of cholangiocarcinomas for more than 3 decades the lack of level I evidence prevents from it being recommended as the first line management across multidisciplinary clinics.

While either modality alone rarely yields survival of more than 12 months, recent reports of improved median survival with combination of high dose radiation and systemic chemotherapy necessitates investigation into role of combination of high dose (chemo) radiation and systemic chemotherapy.

All patients with diagnosis of nonmetastatic unresectable cholangiocarcinoma who fulfill the study eligibility criteria will be evaluated for study participation. Patients will undergo upfront randomization into one of the study arms (systemic chemotherapy alone vs Systemic chemotherapy+ High dose radiation) The study stratification criteria will be done according the primary site i.e. Intrahepatic vs Extrahepatic.

Conditions

Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Systemic Chemotherapy

Irrespective of arm allocation Baseline Positron Emission Tomography(PET) scan and hepatic function assessment will be done. Those randomized to this arm will receive systemic chemotherapy delivered on day 1 and 8 every 3 weekly, with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2. After first 4 cycles patients will undergo repeat Contrast Enhanced Computed Tomography(CECT)/PET scan. If CECT/PET scan shows stable/ responding disease then patients will continue to receive the same chemotherapy. In case of locally progressive/ systemic disease on chemotherapy patients may be considered for second line palliative chemotherapy or best supportive care. The use of radical chemoradiation is not allowed on disease progression in this arm. However palliative radiation may be used.

Group Type: ACTIVE_COMPARATOR

Systemic chemotherapy

Intervention Type: DRUG

This arm will receive maximum 8 cycles of gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 delivered on day 1 and 8 every 3 weekly.

Chemotherapy and radiation

In those randomized to radiation arm with receive high dose radiation with Intensity Modulated Radiation Therapy in addition to systemic and concurrent chemotherapy. The gross tumor will comprise the high dose volume. The adjacent areas of suspected microscopic disease will form the low dose volume. When only external radiation is used the aim will be to deliver 52.5-60 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2) .

Group Type: EXPERIMENTAL

High Dose Radiation

Intervention Type: RADIATION

The aim will be to deliver 52.5-60 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2) .

Systemic chemotherapy

Intervention Type: DRUG

This arm will receive maximum 8 cycles of gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 delivered on day 1 and 8 every 3 weekly.

Interventions

High Dose Radiation

The aim will be to deliver 52.5-60 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2) .

Intervention Type: RADIATION

Systemic chemotherapy

This arm will receive maximum 8 cycles of gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 delivered on day 1 and 8 every 3 weekly.

Intervention Type: DRUG

Other Intervention Names

Radiation; Gemcitabine and Cisplatin regimen

Eligibility Criteria

Inclusion Criteria

• Age >18 years
• Performance Status 0-2
• Tissue diagnosis of adenocarcinoma of the biliary tract. Wherever tissue diagnosis is not feasible in spite of repeated attempts a multidisciplinary consensus on clinicoradiological diagnosis of cholangiocarcinoma (CA 19-9= 100mg/ml with a radiological evidence of malignant stricture) should be made and patients consent should be available for treatment without tissue diagnosis.
• Unresectable disease as determined by hepatobiliary surgical team.
• No evidence of peritoneal or distant metastasis.
• No radiological evidence of paraaortic nodal disease.
• Child A or Child B (score 7)
• Ability to tolerate radical treatment.

Exclusion Criteria

• Multicentric intrahepatic cholangiocarcinoma (however adjacent satellite lesions are permitted)
• Inability to deliver safe radiation due to high tumor/ liver ratio.
• Active cholangitis.
• Expected Survival<6 months.
• Unresolved biliary tract obstruction.
• Inability in deliver systemic chemotherapy (persistent bilirubin>3)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tata Memorial Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Supriya Sastri (chopra)

Associate Professor, Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Supriya Chopra, MD

Role: PRINCIPAL_INVESTIGATOR

ACTREC,Tata Memorial Centre

Locations

Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre

Navi Mumbai, Maharashtra, India

Site Status: RECRUITING

Countries

India

Central Contacts

Supriya Chopra, MD

Role: CONTACT

supriyasastri@gmail.com

09930958309

Supriya Chopra, MD

Role: CONTACT

schopra@actrec.gov.in

09930958309

Facility Contacts

Dr Supriya Chopra, MD

Role: primary

schopra@actrec.gov.in

91-22-27405000 ext. 5491

Other Identifiers

TMC IRB 1457

Identifier Type: -

Identifier Source: org_study_id