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

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Gallbladder Diseases

Bile Duct Diseases

Bile Duct Cancer

Biliary Tract Cancer

Gallbladder Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Gemcitabine

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine Hydrochloride

Nab-paclitaxel

Rachna Shroff

This phase III trial studies how well gemcitabine hydrochloride and cisplatin given with or without nab-paclitaxel work in treating patients with newly diagnosed biliary tract cancers that have spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride, cisplatin, and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not known if giving gemcitabine hydrochloride and cisplatin with or without nab-paclitaxel may work better at treating biliary tract cancers.

PRIMARY OBJECTIVES:

I. To compare overall survival (OS) in patients with untreated, advanced biliary cancers treated with gemcitabine hydrochloride (gemcitabine) and cisplatin (GC) versus those treated with gemcitabine, cisplatin, and nab-Paclitaxel (GCN).

SECONDARY OBJECTIVES:

I. To compare progression-free survival (PFS) in patients treated with GC versus GCN.

II. To compare overall response rate (ORR), complete and partial, confirmed and unconfirmed, in the subset of patients with measurable disease treated with GC versus GCN.

III. To compare disease control rate (confirmed and unconfirmed; complete response + partial response + stable disease) (DCR) in patients treated with GC versus GCN.

IV. To evaluate the frequency and severity of toxicity associated with GC and GCN in the patient population.

V. To explore the correlation between change in cancer antigen 19-9 (CA19-9) levels from baseline to post-treatment (after 3 cycles) and overall response rate, in each treatment arm separately and in the total cohort.

ADDITIONAL OBJECTIVES:

I. To bank tissue and blood for future translational medicine studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and then at the end of year 3.

Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers

A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers

OS will be determined using the log-rank test with stratification by disease site (gallbladder adenocarcinoma versus \[vs.\] intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma), disease stage (locally advanced vs. metastatic), and Zubrod performance status (0 vs. 1). Distributions of overall survival by treatment arm will be estimated using the method of Kaplan-Meier.

Rates of serious toxicities will be compared between arms.

Distributions of PFS will be described using cumulative incidence estimates with differences in these estimates between treatment arms assessed by a stratified Cox regression model.

ORR is defined as confirmed and unconfirmed; complete response + partial response + stable disease. The chi-square test will be used to compare ORR, disease control rate (DCR), and rates of toxicity events across arms. ORR will be assessed in the subset of patients with measurable disease.

The chi-square test will be used to compare ORR, DCR, and rates of toxicity events across arms. Disease control includes confirmed and unconfirmed complete response, confirmed and unconfirmed partial response, and stable disease. In patients with non-measurable disease, disease control will be defined as those who are alive without disease progression.

Correlations between changes in CA19-9 levels from baseline to post-treatment and ORR will be estimated via logistic regression models, both within each treatment arm and in the overall cohort. Analyses will explore the prognostic and predictive values of CA19-9 for disease response.

National Cancer Institute (NCI)

SWOG Cancer Research Network

Anti-Infective Agents

Irinotecan

Trifluridine

Camptothecin

Topoisomerase I Inhibitors

Enzyme Inhibitors

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers	NCT03768414	Stage III Dista... Stage III Gallb... Stage III Intra... Stage IIIA Dist... Stage IIIA Gall... Stage IIIA Intr... Stage IIIB Dist... Stage IIIB Gall... Stage IIIB Intr... Stage IV Distal... Stage IV Gallbl... Stage IV Intrah... Stage IVA Gallb... Stage IVB Gallb... Unresectable Ex... Unresectable Ga... Unresectable In...	Cisplatin Gemcitabine Hyd... Nab-paclitaxel	18 Years -	SWOG Cancer Research Network
Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers	NCT03768414	Stage III Dista... Stage III Gallb... Stage III Intra... Stage IIIA Dist... Stage IIIA Gall... Stage IIIA Intr... Stage IIIB Dist... Stage IIIB Gall... Stage IIIB Intr... Stage IV Distal... Stage IV Gallbl... Stage IV Intrah... Stage IVA Gallb... Stage IVB Gallb... Unresectable Ex... Unresectable Ga... Unresectable In...	Cisplatin Gemcitabine Hyd... Nab-paclitaxel	18 Years -	SWOG Cancer Research Network
Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer	NCT04072445	Advanced Bile D... Advanced Gallbl... Refractory Bile... Refractory Gall... Stage III Dista... Stage III Gallb... Stage III Intra... Stage IIIA Dist... Stage IIIA Gall... Stage IIIA Intr... Stage IIIB Dist... Stage IIIB Gall... Stage IIIB Intr... Stage IV Distal... Stage IV Gallbl... Stage IV Intrah... Stage IVA Gallb... Stage IVB Gallb...	Irinotecan Irinotecan Hydr... Trifluridine an...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for stage iva gallbladder cancer ajcc v8