Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Cholangiocarcinoma

Klatskin Tumor

Liver Neoplasms

Carcinoma, Ductal

Gallbladder Neoplasms

Bile Duct Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Biliary Tract Neoplasms

Biliary Tract Diseases

Gallbladder Diseases

Bile Duct Diseases

Bile Duct Cancer

Biliary Tract Cancer

Gallbladder Cancer

Childhood Hepatocellular Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Bone Density Conservation Agents

Vitamins

Capecitabine

Leucovorin

Fluorouracil

Levoleucovorin

Calcium

Folic Acid

Calcium, Dietary

Trametinib

Vitamin B Complex

Hormones

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Trace Elements

Protein Kinase Inhibitors

Enzyme Inhibitors

Folinic Acid

Folate

Vitamin B9

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.

Laboratory Biomarker Analysis

Leucovorin Calcium

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.

National Cancer Institute (NCI)

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

Partial Response

Unconfirmed Partial Response

Stable/No Response

Increasing Disease

Symptomatic Deterioration

All eligible and analyzable patients with measurable disease.

Objective Response Rate

Progression-free Survival

Overall Study

Anticoagulants

Liver Extracts

Edetic Acid

Pentetic Acid

Chelating Agents

Iron

Iron Chelating Agents

Patients receive gadoxetate disodium IV and then undergo enhanced liver MRI.

Gadoxetate Disodium

Magnetic Resonance Imaging

Gilbert Whang

This pilot clinical trial studies magnetic resonance imaging (MRI) with gadoxetate disodium in measuring tumors in patients with liver cancer. Diagnostic procedures, such as MRI with gadoxetate disodium, may help find and diagnose liver cancer and find out how far the disease has spread. It is not yet known whether MRI with gadoxetate disodium provides a more precise measurement of liver tumors than standard computed tomography (CT).

PRIMARY OBJECTIVES:

I. To evaluate the precision of gadoxetate (gadoxetate disodium)-enhanced MRI in evaluating lesion size.

II. To evaluate if there is a subjective improvement in the delineation of hepatocellular carcinoma (HCC) in the hepatocellular phase of contrast administration.

III. To further assess the sensitivity of gadoxetate-enhanced MRI for the detection of HCC.

SECONDARY OBJECTIVES:

I. To evaluate the reproducibility of various tumor measurement techniques in the evaluation of HCC.

II. To further evaluate how administration of gadoxetate affects diffusion weighted imaging.

OUTLINE:

Patients receive gadoxetate disodium intravenously (IV) and then undergo enhanced liver MRI.

After completion of study, patients are followed up at 2, 4, 8, and 12 months.

MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer

MR Techniques in the Evaluation of Hepatocellular Carcinoma: Gadoxetate

Initially, a random effects analysis of variance (ANOVA) will be performed for each type of image (CT vs. MRI), for each phase (4 for CT and 5 for MRI) and for each method of measuring "size" (1-, 2-, and 3-dimensional) - for a total of 27 ANOVAs. Lesion, radiologist, and replication (for the 20 target lesions measured twice) will all be random effects; the inter-reader and the intra-reader variability will be estimated from these models and 95% confidence intervals will be constructed.

ADC values will be recorded for uninvolved liver parenchyma and for tumors before and after administration of gadoxetate disodium.

University of Southern California

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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)
MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer	NCT02578602	Adult Hepatocel... Advanced Adult ... BCLC Stage 0 Ad... BCLC Stage A Ad... BCLC Stage B Ad... BCLC Stage C Ad... BCLC Stage D Ad... Localized Non-R... Localized Resec...	Gadoxetate Diso... Magnetic Resona...	18 Years -	University of Southern California
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 bclc stage d adult hepatocellular carcinoma