ClinicalTrials.gov
ClinicalTrials.gov Menu

Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02773485
Recruitment Status : Recruiting
First Posted : May 16, 2016
Last Update Posted : May 18, 2016
Sponsor:
Information provided by (Responsible Party):
Supriya Sastri (chopra), Tata Memorial Hospital

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

Condition or disease Intervention/treatment Phase
Cholangiocarcinoma Radiation: High Dose Radiation Drug: Systemic chemotherapy Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 155 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of High Dose Chemoradiation and Systemic Chemotherapy vs Systemic Chemotherapy Alone in Patients With Unresectable Nonmetastatic Cholangiocarcinoma
Study Start Date : May 2015
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Gemcitabine

Arm Intervention/treatment
Active Comparator: 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.
Drug: 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.
Other Name: Gemcitabine and Cisplatin regimen

Experimental: 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) .
Radiation: 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) .
Other Name: Radiation

Drug: 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.
Other Name: Gemcitabine and Cisplatin regimen




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 3 years from completion of study ]
    The trial is designed to assess a 36 month benefit overall survival


Secondary Outcome Measures :
  1. loco-regional progression free survival [ Time Frame: 3 years from completion of accrual ]
    Will compare the loco-regional progression free survival between both the arms

  2. Toxicity Assessment [ Time Frame: upto 3 years ]
    Assessment will be done according to CTCAE v4.0

  3. Quality of Life [ Time Frame: 3 years from completion of accrual ]
    Assessment will be done according to Fact-Hep(version 4)

  4. Surgical Resectability Rates [ Time Frame: 6 weeks from completion of primary treatment ]
    To assess the number of patient who can be taken for surgery in view of good response after treatment

  5. cause specific survival [ Time Frame: 3 years from completion of accrual ]
    Will compare the cause specific survival between both the arms



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02773485


Contacts
Contact: Supriya Chopra, MD 09930958309 supriyasastri@gmail.com
Contact: Supriya Chopra, MD 09930958309 schopra@actrec.gov.in

Locations
India
Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre Recruiting
Navi Mumbai, Maharashtra, India, 410210
Contact: Dr Supriya Chopra, MD    91-22-27405000 ext 5491    schopra@actrec.gov.in   
Principal Investigator: Supriya Chopra, MD         
Sponsors and Collaborators
Tata Memorial Hospital
Investigators
Principal Investigator: Supriya Chopra, MD ACTREC,Tata Memorial Centre

Responsible Party: Supriya Sastri (chopra), Associate Professor, Radiation Oncology, Tata Memorial Hospital
ClinicalTrials.gov Identifier: NCT02773485     History of Changes
Other Study ID Numbers: TMC IRB 1457
First Posted: May 16, 2016    Key Record Dates
Last Update Posted: May 18, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs