A two-arm randomized phase III, open-label prospective non-inferiority study ofirinotecan versus oxaliplatin or 5-FU based chemotherapy mFOLFOX or CAPOX forpatients with locally advanced/ metastatic biliary tract cancers BTC previouslytreated with gemcitabine-cisplatin based chemotherapy.

Phase 3

Recruiting

• Conditions: Disorders of gallbladder, biliarytract and pancreas in diseases classified elsewhere,

• Registration Number: CTRI/2022/01/039568
• Lead Sponsor: Tata Memorial Hospital

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 ofefficacy 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. insubgroup/prognostic comparisons), they will be presented with an accompanyingsignificance level. All p values will be two-sided if not stated otherwise. The suitability ofstatistics will be checked after data entry. If necessary, the statistical method will bemodified accordingly, with a critical discussion of the original and modified results.Response rates (including the primary endpoint), toxicity, and event rates at prespecifiedtime points are calculated as proportions, providing confidence intervals. In case ofcomparison between patient groups, these rates will be analyzed by Fisher’s exact test orchi-square testPFS and OS will be estimated by the Kaplan-Meier method and compared by the log-ranktest. Multivariate prognostic analyses will eventually be performed by suitable regressionmodels (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 sixmonths after the last patient is recruited to study and all follow–up formalities arecompleted.As with first-line therapy, the goals of second-line therapy for advanced/metastatic BTC areto palliate symptoms and improve survival. While the first-line standard has beenestablished in BTC, there has been a scarcity of evidence that further chemotherapy is ofbenefit until recently. A systematic review of fourteen phase 2 studies and nineretrospective studies, comprising 895 patients, was unable to identify an individual activetreatment regimen. Recently published randomized controlled trial in this setting, ABC-06study which showed overall survival benefit (HR 0·69, 95% CI 0·50–0·97, p=0·031) ofsecond-line oxaliplatin and 5-fluorouracil (mFOLFOX) over supportive care alone in patientswith 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).

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-02
• Last Update Posted: 2023-09-02

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 288

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
of India and we need to identify optimal treatment approaches in such patients. In patients	at baseline , at 8-12 weeks and then 2- 3 months post starting treatment .
who have progressed on first-line therapy, there needs to be an optimized approach to	at baseline , at 8-12 weeks and then 2- 3 months post starting treatment .
Patients with advanced BTC are a fragile cohort of patients who need optimal sequencing	at baseline , at 8-12 weeks and then 2- 3 months post starting treatment .
of therapy to maximize outcomes. Additionally, BTC is near-endemic cancer in certain parts	at baseline , at 8-12 weeks and then 2- 3 months post starting treatment .
sequencing therapy to achieve a balance between responses and survival on one side and	at baseline , at 8-12 weeks and then 2- 3 months post starting treatment .
therapy-related toxicities on the other.	at baseline , at 8-12 weeks and then 2- 3 months post starting treatment .

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

TATA MEMORIAL HOSPITAL; 🇮🇳 (Suburban), MAHARASHTRA, India

TATA MEMORIAL HOSPITAL

🇮🇳(Suburban), MAHARASHTRA, India

DR PRABHAT BHARGAVA

Principal investigator

7276174221

bhargava611@gmail.com