| CTRI Number |
CTRI/2022/01/039568 [Registered on: 19/01/2022] Trial Registered Prospectively |
| Last Modified On: |
09/02/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A two-arm randomized phase III, open-label prospective non-inferiority study of
irinotecan versus oxaliplatin or 5-FU based chemotherapy mFOLFOX or CAPOX for
patients with locally advanced/ metastatic biliary tract cancers BTC previously
treated with gemcitabine-cisplatin based chemotherapy.
|
|
Scientific Title of Study
|
A two-arm randomized phase III, open-label prospective non-inferiority study of irinotecan versus oxaliplatin / 5-FU based chemotherapy (mFOLFOX/CAPOX) for patients with locally advanced/ metastatic biliary tract cancers (BTC) previously treated with gemcitabine-cisplatin based chemotherapy. |
| Trial Acronym |
(BTC-SELECT) |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Prabhat Bhargava |
| Designation |
Associate professor medical oncology |
| Affiliation |
tata memorial Hospital |
| Address |
1102 ,11th floor , HBB , TMH , Dr E borges road , Parel
319 , 3rd floor , Medical oncology , HBB , TMH , Dr E borges road , Parel
Mumbai (Suburban)
MAHARASHTRA
400012
India |
| Phone |
7276174221 |
| Fax |
|
| Email |
bhargava611@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Prabhat Bhargava |
| Designation |
Associate professor medical oncology |
| Affiliation |
tata memorial Hospital |
| Address |
1102 , 11th floor , HBB , TMH , Dr E borges road , Parel
319 , 3rd floor , medical oncology , HBB , TMH , Dr E borges road , Parel
Mumbai (Suburban)
MAHARASHTRA
400012
India |
| Phone |
7276174221 |
| Fax |
|
| Email |
bhargava611@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Prabhat Bhargava |
| Designation |
Associate professor medical oncology |
| Affiliation |
tata memorial Hospital |
| Address |
1102 , HBB , TMH , Dr E borges road , Parel
1102 , HBB , TMH , Dr E borges road , Parel
MAHARASHTRA
400012
India |
| Phone |
7276174221 |
| Fax |
|
| Email |
bhargava611@gmail.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Tata mememorial hospital , Dr E borges road , Parel |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DR PRABHAT BHARGAVA |
TATA MEMORIAL HOSPITAL |
Room no 319 , 3rd floor , Homi bhabha building , Tata memorial hospital , DR E BORGES ROAD ,PAREL
Mumbai (Suburban)
MAHARASHTRA |
7276174221
bhargava611@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K87||Disorders of gallbladder, biliarytract and pancreas in diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
irinotecan versus oxaliplatin 5FU based chemotherapy. |
Patients with Un resectable and metastatic BTC refractory to or progressed on first line
therapy will be included in the study. Once initial baseline staging work up and consent are confirmed patients will be randomized to the irinotecan vs mFOLFOX or CAPOX arm.Arm A Irinotecan alone OR
Arm B mFOLFOX/CAPOX.
Irinotecan will be administered at a dose of 240 mg/m2 in 250 to 500 ml 5% D5W/NS over 30 - 90 minutes every 3 weeks. |
| Comparator Agent |
irinotecan versus oxaliplatin 5FU based chemotherapy. |
Patients with Un resectable and metastatic BTC refractory to or progressed on first line therapy will be included in the study. Once initial baseline staging work up and consent are confirmed patients will be randomized to the irinotecan vs mFOLFOX or CAPOX arm.Arm A Irinotecan alone OR Arm B mFOLFOX/CAPOX.
Folfox regime : Oxaliplatin 85 mg/m2 IV in 250 to 500 mL of D5W over 2 hours plus ,
Leucovorin 400 mg/m2 in 250ml NS or D5W over 2 hours plus
5-FU - 2400 mg/m2 IV over 46 hours continuous infusion , 1 cycle, administered every 2 weeks .
Capox regime : Oxaliplatin 130 mg/m2 IV over 120 mins
Capsule Capecitabine 2000 mg/m2, P.O, in two divided doses on days 1–14, 7 days off 1 cycle, administered every 3 weeks |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
Histologically or cytologically confirmed adenocarcinoma of the biliary tract.Either locally advanced (unresectable) / Metastatic disease that is not amenable to curative intent therapy.Patients should have been treated with palliative intent first-line Gemcitabine-based
chemotherapy and should have progressed on the same or stopped 1st line chemotherapy due to poor tolerance, adverse events, or other reasons . If the patient has been treated with curative intent Gemcitabine based therapy, this therapy should have been completed not more than 6 months before trial enrolment. ECOG performance status 0 – 2 . Patients who can give informed consent for the study.The patient does not have any contraindications to receive chemotherapy drugs
(5-Fluorouracil/ Leucovorin/ Capecitabine/ Oxaliplatin/ irinotecan) . Haematological- Hb> 80 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L.Liver functions- bilirubin ≤ 2 x upper limit normal (ULN), AST/ALT ≤ 5 x ULN, S. albumin ≥ 28 g/L . Renal function- Creatinine ≤ 1.5 ULN, Creatinine clearance ≥ 40 mL/min.Women of childbearing age must have a negative pregnancy test before study entry and be using adequate abstinence. This must be continued for 6 months after completion of chemotherapy unless childbearing potential has been terminated by
surgery/radical radiotherapy . .Men must be willing to use adequate abstinence during chemotherapy and until 6 months after chemotherapy.Age ≥18 years and life expectancy >3 months..Adequate biliary drainage, with no evidence of ongoing infection (patients on
maintenance antibiotics are eligible when acute sepsis has resolved) . All patients must be randomized and sites must ensure that patients allocated chemotherapy arm start treatment within 6 weeks of radiological progression.
|
|
| ExclusionCriteria |
| Details |
Active CNS metastasis . Recent MI, NYHA Class III or IV congestive heart failure, ventricular arrhythmias, or uncontrolled blood pressure.Pregnant or breastfeeding patients.Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.History of treatment with 5FU, Capecitabine, oxaliplatin, or Irinotecan.Patients with active second malignancies, apart from skin cancers and cervical
intraepithelial neoplasia. The presence of a curatively treated malignancy for which the patient has completed therapy at least 3 years ago and is now in remission, is considered acceptable.Pleural effusion or ascites that cause respiratory compromise (> CTCAE v.5.0 Grade
2 dyspnea) [Appendix 21.3].Ongoing or active infection (bacterial, fungal, or viral; e.g. hepatitis viral (> Grade 2 CTCAE v. 5.0), or chronic hepatitis B or C requiring treatment with antiviral therapy, or any other active liver disease.Known history of human immunodeficiency virus infection..Unresolved toxicity higher than CTCAE (v.5.0) Grade 1 attributed to any prior
therapy/procedure excluding alopecia, hypothyroidism, and cisplatin-induced
neurotoxicity ≤ Grade 2.
|
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
Pharmacy-controlled Randomization |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
Patients with advanced BTC are a fragile cohort of patients who need optimal sequencing
of therapy to maximize outcomes. Additionally, BTC is near-endemic cancer in certain parts
of India and we need to identify optimal treatment approaches in such patients. In patients
who have progressed on first-line therapy, there needs to be an optimized approach to
sequencing therapy to achieve a balance between responses and survival on one side and
therapy-related toxicities on the other. |
at baseline , at 8-12 weeks and then 2- 3 months post starting treatment . |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To estimate the efficacy of irinotecan vs mFOLFOX/CAPOX as second-line therapy
in advanced/ metastatic biliary tract cancers in terms of Progression-free survival
(PFS).To estimate the efficacy of irinotecan vs mFOLFOX/CAPOX as second-line therapy
in advanced/ metastatic biliary tract cancers in terms of Overall response rate
(ORR).To estimate the efficacy of irinotecan vs mFOLFOX/CAPOX as second-line therapy
in advanced/ metastatic biliary tract cancers in terms of decrease in CA 19-9 serum
levels.To estimate the safety of irinotecan vs mFOLFOX/CAPOX as second-line therapy in
advanced/ metastatic biliary tract cancers in terms of grade 3/4 toxicity as per
CTCAE v5.0.
|
at baseline , at 8-12 weeks and then 2 - 3 months post starting of the treatment . |
|
|
Target Sample Size
|
Total Sample Size="288"
Sample Size from India="288"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
01/02/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="9"
Months="11"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Patients recruited in the study will be evaluated on an intention-to-treat (ITT) analysis.
Patients who have received a single dose of chemotherapy will be included for analysis of
efficacy and analysis.All parameters will be evaluated descriptivelyAfterproviding means, medians, ranges,
standard deviations, and/or confidence intervals. If any p values are calculated (e.g. in
subgroup/prognostic comparisons), they will be presented with an accompanying
significance level. All p values will be two-sided if not stated otherwise. The suitability of
statistics will be checked after data entry. If necessary, the statistical method will be
modified accordingly, with a critical discussion of the original and modified results.Response rates (including the primary endpoint), toxicity, and event rates at prespecified
time points are calculated as proportions, providing confidence intervals. In case of
comparison between patient groups, these rates will be analyzed by Fisher’s exact test or
chi-square testPFS and OS will be estimated by the Kaplan-Meier method and compared by the log-rank
test. Multivariate prognostic analyses will eventually be performed by suitable regression
models (logistic regression, proportional hazard regression model). The following factors
(aside from the nomogram) will be considered for evaluation as prognostic factors.The complete evaluation of results and compilation of statistics will be performed six
months after the last patient is recruited to study and all follow–up formalities are
completed.As with first-line therapy, the goals of second-line therapy for advanced/metastatic BTC are
to palliate symptoms and improve survival. While the first-line standard has been
established in BTC, there has been a scarcity of evidence that further chemotherapy is of
benefit until recently. A systematic review of fourteen phase 2 studies and nine
retrospective studies, comprising 895 patients, was unable to identify an individual active
treatment regimen. Recently published randomized controlled trial in this setting, ABC-06
study which showed overall survival benefit (HR 0·69, 95% CI 0·50–0·97, p=0·031) of
second-line oxaliplatin and 5-fluorouracil (mFOLFOX) over supportive care alone in patients
with disease progression following first-line treatment with cisplatin and gemcitabine.
Although the median overall survival improvement was modest (6·2 months vs 5·3 months).
|