Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Recurrence

Cholangiocarcinoma

Metaplasia

Gallbladder Neoplasms

Bile Duct Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Gallbladder Diseases

Bile Duct Diseases

Bile Duct Cancer

Gallbladder Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Capecitabine

Antimetabolites

Capecitabine 650 mg/m\^2 twice daily (BID), by mouth (PO) at 12 hour intervals, Days 1-14, every 21 days; Gemcitabine 1000 mg/m\^2, intravenous (IV) over 100 minutes, Days 1, 8, every 21 days

650 mg/m\^2 twice daily (BID), by mouth (PO) at 12 hour intervals, Days 1-14, every 21 days

capecitabine

1000 mg/m\^2, intravenous (IV) over 100 minutes, Days 1,8, every 21 days

gemcitabine hydrochloride

Syma Iqbal, MD

Heinz-Josef Lenz, MD

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine with capecitabine in treating patients who have locally advanced or metastatic gallbladder cancer or cholangiocarcinoma.

OBJECTIVES:

* Determine the response rates (confirmed complete and partial responses) in patients with unresectable, locally advanced or metastatic gallbladder cancer or cholangiocarcinoma treated with gemcitabine and capecitabine.
* Determine the overall survival of patients treated with this regimen.
* Determine the quantitative and qualitative toxic effects of this regimen in these patients.
* Determine the feasibility of accruing patients with these disease sites.
* Evaluate, preliminarily, relevant prognostic markers in these disease sites and the prognostic implications as predictors of survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14 and gemcitabine IV over 100 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within approximately 10-20 months.

S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma

A Phase II Trial of Gemcitabine (NSC-613327) and Capecitabine (NSC-712807) in Patients With Unresectable or Metastatic Gallbladder or Cholangiocarcinoma

Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

Measured from time of registration to death, or last contact date

Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included. For each patient, worst grade of each event type is reported.

Only eligible patients who received treatment were evaluable for response and survival outcomes.

To evaluate in a preliminary fashion relevant prognostic markers in gallbladder and cholangiocarcinoma which may have prognostic implications as predictors of survival. Overall survival measured from time of registration to death, or last contact date.

National Cancer Institute (NCI)

SWOG Cancer Research Network

One patient went off study prior to any toxicity assessments and is not evaluable for toxicities.

Gemcitabine and Capecitabine

Capecitabine + Gemcitabine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Statistician

Confirmed Partial Response

Unconfirmed Partial Response

Stable Disease

Progression

Symptomatic Deterioration

Early Death

Inadequate Assessment

All eligible patients who started treatment were included in assessing response estimates.

Response

Overall Survival

ALT, SGPT (serum glutamic pyruvic transaminase)

AST,SGOT (serum glutamic oxaloacetic transaminase)

Albumin, serum-low (hypoalbuminemia)

Alkaline phosphatase

Anorexia

Ascites (non-malignant)

Bilirubin (hyperbilirubinemia)

Constipation

Creatinine

Dehydration

Diarrhea

Dysphagia (difficulty swallowing)

Fatigue (asthenia, lethargy, malaise)

Hemoglobin

Hemolysis

Hemorrhage, GI - Esophagus

Infection w/Grade 3-4 neutrophils - Upper airway

Infection with normal ANC or Grade 1-2 neutrophils

Leukocytes (total WBC)

Mucositis/stomatitis (clinical exam) - Oral cavity

Mucositis/stomatitis (function/symp)-Oral cavity

Muscle weakness (not due to neuropathy)

Nausea

Neutrophils/granulocytes (ANC/AGC)

Pain - Abdomen NOS

Pain - Joint

Pain - Muscle

Pain - Tumor pain

Platelets

Potassium, serum-low (hypokalemia)

Rash: hand-foot skin reaction

Supraventricular nodal arrhythmia

Thrombosis/thrombus/embolism

Vomiting

Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

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

Eligible

Eligible and Analyzable

Patients with advanced disease accrued between September 2003 to April 2005

Accrual of Patients With This Disease Site

TS 3' +/+ (N=14)

TS 3' +/- (N=6)

TS 3' -/- (N=2)

TS 5' Low functional significance (N=16)

TS 5' Intermediate functional significance (N=16)

MTHFR C677T - C/C (N=11)

MTHFR C677T - C/T (N=11)

MTHFR A1298C - A/A (N=11)

MTHFR A1298C - A/C (N=8)

MTHFR A1298C - C/C (N=3)

RRMI G/A - G/G (N=9)

RRMI G/A - G/A (N=10)

RRMI G/A - A/A (N=3)

CDA A79C - A/A (N=8)

CDA A79C - A/C (N=12)

CDA A79C - C/C (N=1)

Eligible patients who received genotyping were included in this analysis.

Median Survival Time for Participants With Relevant Biologic Markers

Overall Study

Liver Neoplasms

Liver Diseases

Biliary Tract Cancer

Primary Liver Cancer

Hematinics

Liver Extracts

clinical observation

adjuvant therapy

Clive Stubbs

RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving capecitabine after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether capecitabine is more effective than observation in treating biliary tract cancer.

PURPOSE: This randomized phase III trial is studying capecitabine to see how well it works compared with observation in treating patients with biliary tract cancer.

OBJECTIVES:

Primary

* To determine whether adjuvant chemotherapy with capecitabine has any effect on 2-year survival compared to expectant treatment alone (observation) in patients who have undergone a macroscopically complete surgical resection of a biliary tract cancer.

Secondary

* To compare capecitabine versus observation in terms of 5-year survival, relapse-free survival, toxicity, quality of life, and health economics.

OUTLINE: This is a multicenter, prospective, randomized study. Patients are stratified according to surgical center, disease site (hilar/extrahepatic cholangiocarcinoma vs intrahepatic cholangiocarcinoma vs gallbladder vs intrapancreatic/common bile duct), type of resection (R0 vs R1), and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral capecitabine twice a day on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients undergo expectant treatment (observation). Quality of life is assessed at baseline, every 3 months for 1 year, and then every 6 months for 1 year.

All patients are followed for up to 5 years post-randomization.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study.

Capecitabine or Observation After Surgery in Treating Patients With Biliary Tract Cancer

A Randomised Clinical Trial Evaluating Adjuvant Chemotherapy With Capecitabine Compared to Expectant Treatment Alone (Observation) Following Surgery for Biliary Tract Cancer

University Hospital Southampton NHS Foundation Trust

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma	NCT00033540	Extrahepatic Bi... Gallbladder Can...	capecitabine gemcitabine hyd...	18 Years -	SWOG Cancer Research Network
S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma	NCT00033540	Extrahepatic Bi... Gallbladder Can...	capecitabine gemcitabine hyd...	18 Years -	SWOG Cancer Research Network
Capecitabine or Observation After Surgery in Treating Patients With Biliary Tract Cancer	NCT00363584	Extrahepatic Bi... Gallbladder Can... Liver Cancer	capecitabine clinical observ... adjuvant therap...	18 Years -	National Cancer Institute (NCI)
Capecitabine or Observation After Surgery in Treating Patients With Biliary Tract Cancer	NCT00363584	Extrahepatic Bi... Gallbladder Can... Liver Cancer	capecitabine clinical observ... adjuvant therap...	18 Years -	National Cancer Institute (NCI)
S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma	NCT00033540	Extrahepatic Bi... Gallbladder Can...	capecitabine gemcitabine hyd...	18 Years -	SWOG Cancer Research Network

Spots Global Cancer Trial Database for squamous cell carcinoma of the gallbladder