Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Cholangiocarcinoma

Carcinoma, Ductal

Biliary Tract Neoplasms

Gallbladder Neoplasms

Bile Duct Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Gallbladder Diseases

Bile Duct Diseases

Adenocarcinoma

Bile Duct Cancer

Biliary Tract Cancer

Gallbladder Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Irinotecan

Trifluridine

Camptothecin

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Irinotecan Hydrochloride

Trifluridine and Tipiracil Hydrochloride

Amit Mahipal

This phase II trial studies how well trifluridine/tipiracil and irinotecan work in treating patients with biliary tract cancer that has spread to other places in the body (advanced) and has not responded to treatment (refractory). Trifluridine/tipiracil and irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. Determine the efficacy of trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) in combination with irinotecan hydrochloride (irinotecan) in patients with refractory biliary tract cancers using progression-free survival (PFS) at 16 weeks.

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers through adverse event monitoring.

II. Further explore the efficacy of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers by overall response rates (ORR), disease control rates (DCR), and overall survival (OS).

CORRELATIVE RESEARCH:

I. To determine if the number of circulating tumor cells (CTCs) or the level of cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline is prognostic or predictive to the response to therapy.

II. To determine if changes in CTCs or cfDNA correlate with efficacy endpoints. III. To determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine/tipiracil plus irinotecan.

IV. To evaluate the role of thymidine kinase 1 (TK1) in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.

EXPLORATORY RESEARCH:

I. To evaluate patients who received prior treatment with fluorouracil (5-FU) independently from the entire population in the following areas: PFS, safety and tolerability, ORR, DCR, and OS.

OUTLINE:

Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and irinotecan hydrochloride (IV) over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 2 years after study registration.

Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer

Phase II Trial of Trifluridine/Tipiracil in Combination With Irinotecan in Biliary Tract Cancers

Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.

Will determine if change in CTCs or cfDNA will correlate with efficacy endpoints.

Will determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) plus irinotecan hydrochloride (irinotecan).

Will evaluate the role of TK1 in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.

Will be defined as the proportion of evaluable patients who are progression-free (stable disease, partial response, complete response) at 16 weeks and assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Will be defined as the proportion of patients who experience either a partial response or complete response as their best response. ORR will be reported descriptively and a 95% confidence interval will be reported.

Will be defined as the proportion of patients who experience a partial response, complete response, or have stable disease as their best response. DCR will be reported descriptively and a 95% confidence interval will be reported.

Will be determined based on RECIST v 1.1. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported. Patients will be censored at the last disease assessment date.

Will be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported. Patients will be censored at the date patient was last known to be alive.

The maximum grade for each type of adverse event by patient will be summarized by frequencies and percentages using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

National Comprehensive Cancer Network

Mayo Clinic

Trifluridine and Tipiracil Hydrochloride: Given PO

Treatment (Trifluridine and Tipiracil, Irinotecan)

Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.\>

\> Irinotecan: Given IV\>

\> Irinotecan Hydrochloride: Given IV\>

\> Trifluridine and Tipiracil Hydrochloride: Given PO

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Prior treatment

Extrahepatic biliary tract cancer

Gallbladder

Intrahepatic

Primary Site of Tumor

Moderately

Poorly differentiated

Degree of differentiation

ECOG = 0: Fully active, able to carry on all pre-disease performance without restriction.

ECOG = 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.

ECOG = 0 is better. ECOG = 1 is worse.

ECOG Performance Status (PS)

Prior treatment with fluoropyrimidine based regimen

Bone

Liver

Peritoneum

Lung

Nodal

Abdominal Wall

Interaortocaval LN

Pancreas

Perisplenic and Perihepatic

Soft tissue, adrenal gland.

abdominal wall, mesenteric node.

hepatic duct

Metastatic Sites

Cholangiocarcinoma, intrahepatic and extrahepatic bile ducts (adenocarcinoma)

Gall Bladder Carcinoma

MedDRA disease code

Dr. Amit Mahipal

Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

\>

\> Irinotecan: Given IV

\>

\> Irinotecan Hydrochloride: Given IV

\>

\> Trifluridine and Tipiracil Hydrochloride: Given PO

Progression-free Survival (PFS)

7 patients went off treatment early on and weren't evaluated for response post-baseline

Overall Response Rate (ORR)

Disease Control Rate (DCR)

Overall Survival (OS)

Grade 3+ AE

Grade 4 AE

Grade 5 AE

Number of Participants With Adverse Events

Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (cfDNA) at Baseline

Change in CTCs or cfDNA

Correlation of Response

Prediction of Clinical Benefit by Thymidine Kinase 1 (TK1)

Overall Study

Spots Global Cancer Trial Database for advanced gallbladder carcinoma