Gemcitabine Plus Pemetrexed Disodium in Treating Patients With Unresectable or Metastatic Biliary Tract or Gallbladder Cancer

Liver Cancer Clinical Trial

Official title:

Phase I/II Trial Of Gemcitabine And ALIMTA In Patients With Measurable Or Evaluable, Unresectable Or Metastatic Biliary Tract Carcinoma (Intrahepatic, Extrahepatic, Ampulla Or Vater) And Gallbladder Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00059865
• Other study ID #: N9943
• Secondary ID: NCCTG-N9943CDR00
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 6, 2003
• Last updated: December 5, 2016
• Start date: January 2004
• Est. completion date: February 2008

Study information

• Verified date: December 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy such as gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining gemcitabine with pemetrexed disodium may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of gemcitabine when given together with pemetrexed disodium to see how well it works in treating patients with unresectable or metastatic biliary tract or gallbladder cancer.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of gemcitabine when administered with pemetrexed disodium in patients with unresectable or metastatic biliary tract or gallbladder cancer. (Phase I closed to accrual as of Oct. 2005.)

• Determine the 6-month survival rate of patients treated with this regimen.

• Determine the best objective tumor response rate and duration of best objective tumor response in patients treated with this regimen.

• Determine the time to progression and overall survival of patients treated with this regimen.

• Determine the toxic effects of this regimen in these patients.

• Determine the individual patient variation in toxicity of and/or response to this regimen due to genetic differences in proteins involved in drug response in these patients.

OUTLINE: This is a multicenter phase I dose-escalation study of gemcitabine followed by a phase II study.

• Phase I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity (phase I closed to accrual as of October 2005).

Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive pemetrexed disodium as in phase I and gemcitabine at the recommended phase II dose.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: February 2008
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

• One of the following histologically or cytologically confirmed cancers not amenable to treatment with combined chemotherapy and radiotherapy:

• Biliary tract (intrahepatic, extrahepatic, or ampulla of Vater) carcinoma

• Gallbladder carcinoma

• Unresectable or metastatic disease

• No CNS metastases

• Prior brain metastases treated with surgery or radiosurgery allowed provided treatment was completed at least 4 weeks ago and there is no evidence of CNS progression

• No clinically significant pericardial or pleural effusion or ascites unless able to be drained before study entry

• Performance status - ECOG 0-2

• At least 3 months

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin no greater than 3 times upper limit of normal (ULN)

• AST no greater than 5 times ULN

• Creatinine no greater than 1.5 times ULN

• Creatinine clearance at least 45 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer

• Able to tolerate folic acid, corticosteroids, or cyanocobalamin supplements

• More than 4 weeks since prior biologic or immunologic therapy

• No prior biologic or immunologic therapy for metastatic disease

• No concurrent immunotherapy

• No concurrent colony-stimulating factors during course 1

• No prior chemotherapy for metastatic disease

• No prior gemcitabine

• Prior chemoembolization allowed provided the following are true:

• At least 4 weeks since prior chemoembolization

• Evidence of new tumor growth since therapy

• At least 6 months since prior chemotherapy used as a radiosensitizer (in adjuvant setting or for locally advanced disease)

• No other concurrent chemotherapy

• Prior radiofrequency ablation allowed provided the following are true:

• At least 4 weeks since prior radiofrequency ablation

• Evidence of new tumor growth since therapy

• No prior radiotherapy to 25% or more of the bone marrow

• More than 4 weeks since prior radiotherapy

• No concurrent radiotherapy

• Prior embolization allowed provided the following are true:

• At least 4 weeks since prior embolization

• Evidence of new tumor growth since therapy

• No prior pemetrexed disodium

• No aspirin or nonsteroidal anti-inflammatory drugs for at least 2 days (5 days for long-acting agents [e.g., piroxicam]) before, during, and for at least 2 days after administration of pemetrexed disodium

• No concurrent cyclo-oxygenase-2 inhibitors

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms
• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• gemcitabine hydrochloride

• pemetrexed disodium

Locations

Country	Name	City	State
United States	AnMed Cancer Center	Anderson	South Carolina
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Southwest Medical Center	Liberal	Kansas
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Park Nicollet Cancer Center	St. Louis Park	Minnesota
United States	United Hospital	St. Paul	Minnesota
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Alberts SR, Foster NR, McWilliams RR, et al.: NCCTG phase I/II trial (N9943) of gemcitabine and pemetrexed in patients with unresectable or metastatic biliary tract carcinoma and gallbladder carcinoma: interim results. [Abstract] American Society of Clini

Alberts SR, Sande JR, Foster NR, Quevedo FJ, McWilliams RR, Kugler JW, Fitch TR, Jaslowski AJ. Pemetrexed and gemcitabine for biliary tract and gallbladder carcinomas: a North Central Cancer Treatment Group (NCCTG) phase I and II Trial, N9943. J Gastroint — View Citation

McWilliams RR, Foster NR, Quevedo FJ, et al.: NCCTG phase I/II trial (N9943) of gemcitabine and pemetrexed in patients with biliary tract or gallbladder carcinoma: phase II results. [Abstract] J Clin Oncol 25 (Suppl 18): A-4578, 2007.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival after 6 months of treatment		Up to 6 months	No
Secondary	Response as assessed by RECIST criteria every 8-16 weeks		Up to 16 weeks	No
Secondary	Toxicity as assessed by CTC v3 every 4 weeks		Up to 4 weeks	Yes