Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma

Prospective Phase II Study of Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma

Previous reports suggest benefit of neoadjuvant chemotherapy/chemoradiation treatment for borderline resectable cholangiocarcinoma. This study is a single center prospective phase II study of neoadjuvant chemotherapy with mFOLFOXIRI in patients with borderline resectable cholangiocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: mFOLFOXIRI

Detailed Description

Previous reports suggest benefit of neoadjuvant chemotherapy/chemoradiation treatment for borderline resectable cholangiocarcinoma.

This study is a single center prospective phase II study of neoadjuvant chemotherapy with mFOLFOXIRI in patients with borderline resectable cholangiocarcinoma.

This phase 2 trial was designed to enroll 25 patients with BRCC who were assigned to mFOLFOXIRI neoadjuvant chemotherapy. The primary endpoint was the overall response rate.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jarin Chindaprasirt, MD; Phone Number: 6643366562; Email: jarich@kku.ac.th
• Study Contact Backup: Name: Jaruda Sringam, Master; Phone Number: 6643366562; Email: talnurse8@gmail.com

Study Locations

• Thailand
  • Khon Kaen, Thailand, 40002
    • Recruiting
    • Jarin Chindaprasirt
    • Principal Investigator: Jarin Chindaprasirt, MD
    • Contact: Jureerat Ratanaphet, Master; Phone Number: 6643366592; Email: jurepr@kku.ac.th
    • Sub-Investigator: Aumkhae Sookprasert, MD
    • Sub-Investigator: Kosin Wirasorn, MD
    • Sub-Investigator: Attapol Titapun, MD
    • Sub-Investigator: Kulyada Somsap, MD
    • Sub-Investigator: Watcharin Loilome, MD
    • Sub-Investigator: Narong Kuntikheo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥ 18 years old at the time of informed consent
2. Diagnosed with cholangiocarcinoma and the disease is measurable by RECIST 1.1 criteria
3. ECOG performance status of 0 or 1
4. No distant metastasis
5. The disease is either resectable or potentially resectable

6. Patients must have adequate organ function as defined by the following laboratory values at study entry:

   Hemoglobin ≥ 8 g/dL (transfusions are acceptable) ANC ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L AST/ALT ≤ 3 x ULN Total bilirubin ≤ 2.5 mg/dL Creatinine clearance ≥ 50 mL/min (estimated by Cockcroft-Gault or measured)

7. Women of childbearing potential definition (WOCBP) and men must agree to use adequate contraception prior, to study entry, for the duration of study participation, and 3 months after the end of treatment.
8. WOCBP must have a negative serum or urine pregnancy test prior to initiation of treatment.

Exclusion Criteria:

1. > 75 years old
2. Prior therapy for cholangiocarcinoma with either surgery, radiation or chemotherapy
3. Other malignancies except for the following: adequately treated cervical carcinoma in situ and treated basal cell carcinoma.
4. Hypersensitivity to 5FU, oxaliplatin (or other platinum agents), irinotecan (or to their excipients).
5. Pregnant or lactating women.
6. Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
7. Liver disease including but not limited to cirrhosis, primary sclerosing cholangitis, future liver remnant of less than 20-30%
8. Comorbidity including but not limited to active clinically serious infections, congestive heart failure, life-threatening arrhythmia
9. known HIV positive
10. Baseline peripheral neuropathy/paresthesia grade ≥ 2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mFOLFOXIRI; mFOLFOXIRI consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours Leucovorin, 400 mg/m2, IV over 2 hours Irinotecan, 150 mg/m2, IV over 90 minutes 5 FU, 400 mg/m2, IV bolus 5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection each 14 day cycle, for 6 cycles	Drug: mFOLFOXIRI; mFOLFOXIRI consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours; Leucovorin, 400 mg/m2, IV over 2 hours; Irinotecan, 150 mg/m2, IV over 90 minutes; 5 FU, 400 mg/m2, IV bolus; 5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection each 14 day cycle, for 6 cycles; Other Names: Leucovorin; Irinotecan; Oxaliplatin; Fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of overall response evaluated by MRI or CT	The rate of response evaluated by MRI or CT according to RECIST 1.1 criteria	Up to 15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resectability rate	The rate of patients who can successfully undergo surgery after chemotherapy	Up to 24 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	every 15 days for approximately 24 weeks

Collaborators and Investigators

• Sponsor: Khon Kaen University
• Investigators: Principal Investigator: Jarin Chindaprasirt, MD, Khon Kaen University

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2018
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Chemotherapy; Neoadjuvant; Bile duct cancer; Potentially resectable
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan
• Other Study ID Numbers: HE611336

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No