CholangiocarcinomaPhase 3NCT02773485
Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma
A Phase 3 study testing High Dose Radiation and Systemic chemotherapy in people with Cholangiocarcinoma, run by Tata Memorial Hospital at 1 site in India.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma
- What is being tested?
- High Dose Radiation and Systemic chemotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 1 siteIndia
- Study dates
- May 2015to Jun 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre
Navi Mumbai, Maharashtra, 410210
Dr Supriya Chopra, MD, 91-22-27405000 ext. 5491, schopra@actrec.gov.in
Supriya Chopra, MD
About this study
Official title: Phase III Randomized Trial of High Dose Chemoradiation and Systemic Chemotherapy vs Systemic Chemotherapy Alone in Patients With Unresectable Nonmetastatic Cholangiocarcinoma
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
Read the 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
- Being tested
- High Dose Radiation, Systemic chemotherapy
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Dose RadiationRadiation
Also called 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 chemotherapyDrug
Also called Gemcitabine and Cisplatin regimen
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.
| Study group | Role | What they receive |
|---|---|---|
| Systemic Chemotherapy | Active comparator | 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. Receives: Drug: Systemic chemotherapy |
| Chemotherapy and radiation | Experimental | 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) . Receives: Radiation: High Dose Radiation; Drug: Systemic chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
The trial is designed to assess a 36 month benefit overall survival
Measured: 3 years from completion of study
Secondary outcomes (5)
loco-regional progression free survival
Will compare the loco-regional progression free survival between both the arms
Measured: 3 years from completion of accrual
Toxicity Assessment
Assessment will be done according to CTCAE v4.0
Measured: upto 3 years
Quality of Life Assessment of patients over a period of time
Assessment will be done according to Fact-Hep(version 4)
Measured: 3 years from completion of accrual
Surgical Resectability Rates
To assess the number of patient who can be taken for surgery in view of good response after treatment
Measured: 6 weeks from completion of primary treatment
cause specific survival
Will compare the cause specific survival between both the arms
Measured: 3 years from completion of accrual
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2016 (estimated)
- Study startMay 2015
- Primary completionJun 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 155 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Supriya Sastri (chopra), Tata Memorial Hospital
- Investigators
- Supriya Chopra, MD, Principal investigator, ACTREC,Tata Memorial Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02773485
- Sponsor's protocol ID
- TMC IRB 1457
- Status last verified
- Oct 2022
- First submitted
- 8 Mar 2016
- Last updated
- 21 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Randomized Trial of High Dose Chemoradiation and Systemic Chemotherapy vs Systemic Chemotherapy Alone in Patients With Unresectable Nonmetastatic Cholangiocarcinoma
- ClinicalTrials.gov ID
- NCT02773485
- Acronym / sponsor ID
- TMC IRB 1457
- Conditions
- Cholangiocarcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 155 participants (estimated)
- Lead sponsor
- Tata Memorial HospitalOther government
- Study start
- May 2015
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 16 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Systemic Chemotherapy | Active comparator | Drug: Systemic chemotherapyIrrespective 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. |
| Chemotherapy and radiation | Experimental | Radiation: High Dose Radiation, Drug: Systemic chemotherapyIn 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) . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High Dose RadiationAlso: RadiationThe 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 | Chemotherapy and radiation |
| Systemic chemotherapyAlso: Gemcitabine and Cisplatin regimenThis 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. | Drug | Chemotherapy and radiation, Systemic Chemotherapy |
Primary outcome
Overall Survival
Time frame: 3 years from completion of study
The trial is designed to assess a 36 month benefit overall survival
5 secondary outcomes
loco-regional progression free survival
Time frame: 3 years from completion of accrual
Toxicity Assessment
Time frame: upto 3 years
Quality of Life Assessment of patients over a period of time
Time frame: 3 years from completion of accrual
Surgical Resectability Rates
Time frame: 6 weeks from completion of primary treatment
cause specific survival
Time frame: 3 years from completion of accrual
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Supriya Chopra, MD principal investigator
ACTREC,Tata Memorial Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing High Dose Radiation and Systemic chemotherapy in people with Cholangiocarcinoma, run by Tata Memorial Hospital at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Supriya Chopra, MD (09930958309, supriyasastri@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 3 years from completion of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2022.