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

Carcinoma, Ductal

Bile Duct Neoplasms

Liver Neoplasms

Disease Attributes

Liver Diseases

Bile Duct Diseases

Biliary Tract Cancer

Patients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Akt Inhibitor MK2206

Diagnostic Laboratory Biomarker Analysis

Pharmacological Study

Tanios Bekaii-Saab

This phase II trial is studying how well MD2206 works in treating patients with advanced refractory biliary cancer that cannot be removed by surgery.

PRIMARY OBJECTIVES:

I. To evaluate the objective response rate (complete and partial response), as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, in patients with advanced refractory biliary cancers (BC) receiving Akt inhibitor MK2206 (MK2206).

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events and tolerability of the regimen in patients with advanced refractory BC receiving MK2206.

II. To determine the overall and progression-free survival of patients with advanced refractory BC receiving MK2206.

III. To determine the presence of genetic mutations of PI3-kinase/ Akt pathway signaling-pathway genes relevant to BC and how these correlate with objective response to treatment with MK2206.

IV. To determine the pharmacokinetic and pharmacogenetic profile as a way of assessing inter-individual variability as well as how these relate to clinical outcomes.

V. To determine genetic variants and mutations in genes encoding drug-metabolizing enzymes and transporters, and genes involved in tumor biology, and how these may be related to response to treatment.

OUTLINE: This is a multicenter study.

Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for pharmacokinetic, pharmacogenetic, and other correlative studies. Previously collected tumor tissue is also analyzed.

After completion of study therapy, patients are followed up for 4 weeks.

MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery

A Multi-Institutional Phase II Study of the Akt Inhibitor MK-2206 in Refractory Biliary Cancers

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Severity of adverse events is graded according to the NCI CTCAE 4.0.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 was utilized for Adverse Event reporting.

Patients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Akt Inhibitor MK2206: Given PO

Diagnostic Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Treatment (Akt Inhibitor MK2206)

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Intrahepatic

Gallbladder

Extrahepatic

Disease site

PS 0

PS 1

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

PS 0 defined as Normal activity. Fully active, able to carry on all pre-disease performance without restriction.

PS 1 defined as Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework, office work).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery	NCT01425879	Advanced Adult ... Localized Non-R... Recurrent Adult... Recurrent Gallb... Stage IV Distal... Stage IV Gallbl... Unresectable Ex... Unresectable Ga...	Akt Inhibitor M... Diagnostic Labo... Pharmacological...	18 Years -	National Cancer Institute (NCI)

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