Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Cholangiocarcinoma

Adenocarcinoma

Pancreatic Neoplasms

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gallbladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Stomach Diseases

Biliary Tract Neoplasms

Biliary Tract Diseases

Gallbladder Diseases

Pancreatic Cancer

Bile Duct Cancer

Stomach Cancer

Gallbladder Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Bone Density Conservation Agents

Hematinics

Vitamins

Paclitaxel

Albumin-Bound Paclitaxel

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Calcium

Calcium, Dietary

Tubulin Modulators

Antimitotic Agents

Hormones

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

Patients receive FOLFIRABRAX comprising paclitaxel albumin-stabilized nanoparticle formulation IV over 0.5 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 1.5 hours, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 4 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.

Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Leucovorin Calcium

Irinotecan Hydrochloride

Laboratory Biomarker Analysis

Manish Sharma

This phase I/II trial studies the side effects of genetic analysis-guided dosing of paclitaxel albumin-stabilized nanoparticle formulation, fluorouracil, leucovorin calcium, and irinotecan hydrochloride (FOLFIRABRAX) in treating patients with gastrointestinal cancer that has spread to other parts of the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, fluorouracil, leucovorin calcium, and irinotecan hydrochloride, 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. Genetic analysis may help doctors determine what dose of irinotecan hydrochloride patients can tolerate.

PRIMARY OBJECTIVES:

I. To determine the dose-limiting toxicity (DLT) rate in cycle #1 in each of three uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype groups (\*1/\*1, \*1/\*28, \*28/\*28) using genotype-guided dosing of irinotecan (irinotecan hydrochloride) as part of the FOLFIRABRAX regimen.

SECONDARY OBJECTIVES:

I. To determine the cumulative dose of each chemotherapy drug (nab-paclitaxel \[paclitaxel albumin-stabilized nanoparticle formulation\], irinotecan, 5-FU \[fluorouracil\]) administered in each genotype group.

II. To determine the response rates (in patients with measurable disease) by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) for each different disease (pancreatic cancer, biliary tract cancer, esophageal/gastric cancer, adenocarcinoma of unknown primary) treated in the study.

OUTLINE:

Patients receive FOLFIRABRAX comprising paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 0.5 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 1.5 hours, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 4 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.

Genetic Analysis-Guided Dosing of FOLFIRABRAX in Treating Patients With Advanced Gastrointestinal Cancer

A Genotype-Guided Dosing Study of FOLFIRABRAX in Previously Untreated Patients With Advanced Gastrointestinal Malignancies

Adverse events will be summarized by type, grade, and attribution.

These results will be compared descriptively to appropriate historical controls. Exact 90% confidence intervals will be generated for the response rates.

The means and standard deviations for patients in each genotype group will be reported.

National Cancer Institute (NCI)

University of Chicago

Symptoms and General Pathology

Carcinoma, Hepatocellular

Recurrence

Klatskin Tumor

Liver Neoplasms

Carcinoma, Ductal

Bile Duct Neoplasms

Disease Attributes

Liver Diseases

Bile Duct Diseases

Biliary Tract Cancer

Childhood Hepatocellular Carcinoma

Capecitabine

Trametinib

Protein Kinase Inhibitors

Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15 (courses repeat every 28 days); or B) capecitabine PO BID on days 1-14 (courses repeat every 21 days). Patients treated until disease progression or unacceptable toxicity.

Richard Kim

This randomized phase II trial studies how well trametinib or combination chemotherapy works in treating patients with refractory or advanced biliary or gallbladder cancer or that cannot be removed by surgery. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and capecitabine, 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 yet known whether giving trametinib is more effective than combination chemotherapy in treating patients with biliary or gallbladder cancer.

PRIMARY OBJECTIVES:

I. To assess overall survival (OS) in patients with refractory advanced biliary cancer randomized to Arm 1: trametinib compared to those randomized to Arm 2: chemotherapy (either 5-fluorouracil \[fluorouracil\] and leucovorin \[leucovorin calcium\] or capecitabine).

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events of trametinib in this patient population.

II. To assess response rate (RR) and progression-free survival (PFS) in patients randomized to Arm 1: trametinib and patients randomized to Arm 2: chemotherapy (fluorouracil \[5-FU\] or capecitabine in this patient population).

TERTIARY OBJECTIVES:

I. To determine if a 16-gene expression signature is predictive of mitogen-activated protein kinase kinase (MEK) efficacy as evidenced by improved RR, PFS, and OS.

II. To evaluate the effects of trametinib on the inflammatory cytokine and explore potential associations with response rate and survival.

III. To estimate lean soft tissue and fat mass weight gain as a result of treatment with trametinib vs. capecitabine in patients with advanced refractory biliary cancer.

IV. To bank tissue samples for other future correlative studies including next generation sequencing and whole genome methylation assays. NOTE: These potential future correlative studies will not be performed until an amended protocol with relevant detailed information including specific arms and assays is approved by Cancer Therapy Evaluation Program (CTEP).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive trametinib orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive 1 of 2 treatment regimens at the discretion of the investigator.

ARM IIA: Patients receive leucovorin calcium intravenously (IV) over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM IIB: Patients receive capecitabine PO twice daily (BID) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery

Randomized Phase II Trial of Single Agent MEK Inhibitor Trametinib (GSK1120212) Vs 5-Fluorouracil or Capecitabine in Refractory Advanced Biliary Cancer

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Adverse event reporting followed the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.

Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.

Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or B) capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Chemotherapy

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

5FU/LV

Planned Chemotherapy

Gall bladder

Site of Disease

All eligible and analyzable patients are included.

SWOG Statistician

Overall Survival

Alanine aminotransferase increased

Anemia

Ascites

Aspartate aminotransferase increased

Blood bilirubin increased

Colitis

Fatigue

Gastric ulcer

Gastritis

Gastrointestinal disorders - Other, specify

Generalized muscle weakness

Hepatobiliary disorders - Other, specify

Hyponatremia

Infections and infestations - Other, specify

Mucositis oral

Neutrophil count decreased

Pain in extremity

Palmar-plantar erythrodysesthesia syndrome

Sepsis

Thromboembolic event

Urinary tract infection

Vomiting

Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity

Eligible patients who received any treatment and were assessed for adverse events are included in this summary. One patient was hospitalized prior to receiving protocol treatment and was not assessed for adverse events.

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genetic Analysis-Guided Dosing of FOLFIRABRAX in Treating Patients With Advanced Gastrointestinal Cancer	NCT02333188	Adenocarcinoma ... Adult Cholangio... Gallbladder Car... Gastric Adenoca... Malignant Gastr... Metastatic Panc... Pancreatic Aden... Stage III Ampul... Stage III Pancr... Stage IIIA Gall... Stage IIIA Gast... Stage IIIB Gall... Stage IIIB Gast... Stage IV Ampull... Stage IV Gallbl... Stage IV Gastri... Stage IV Pancre...	Paclitaxel Albu... Leucovorin Calc... Irinotecan Hydr... Fluorouracil Laboratory Biom...	18 Years -	University of Chicago
Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery	NCT02042443	Adult Cholangio... Advanced Adult ... BCLC Stage C Ad... BCLC Stage D Ad... Hilar Cholangio... Localized Non-R... Recurrent Adult... Recurrent Child... Recurrent Extra... Recurrent Gallb... Stage II Gallbl... Stage III Child... Stage IIIA Gall... Stage IIIB Gall... Stage IV Childh... Stage IV Distal... Stage IVA Gallb... Stage IVB Gallb... Unresectable Ex...	Capecitabine Fluorouracil Laboratory Biom... Leucovorin Calc... Trametinib	-	National Cancer Institute (NCI)
Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery	NCT02042443	Adult Cholangio... Advanced Adult ... BCLC Stage C Ad... BCLC Stage D Ad... Hilar Cholangio... Localized Non-R... Recurrent Adult... Recurrent Child... Recurrent Extra... Recurrent Gallb... Stage II Gallbl... Stage III Child... Stage IIIA Gall... Stage IIIB Gall... Stage IV Childh... Stage IV Distal... Stage IVA Gallb... Stage IVB Gallb... Unresectable Ex...	Capecitabine Fluorouracil Laboratory Biom... Leucovorin Calc... Trametinib	-	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for adult cholangiocarcinoma