Gemcitabine Plus Pemetrexed Disodium in Treating Patients With Unresectable or Metastatic Biliary Tract or Gallbladder Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Extrahepatic Bile Duct Cancer Gallbladder Cancer Liver Cancer	Drug: gemcitabine hydrochloride Drug: pemetrexed disodium	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Liver Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Pemetrexed Pemetrexed disodium

Genetic and Rare Diseases Information Center resources: Liver Cancer Gallbladder Cancer Bile Duct Cancer

U.S. FDA Resources

Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:

Survival after 6 months of treatment [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response as assessed by RECIST criteria every 8-16 weeks [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: No ]
Toxicity as assessed by CTC v3 every 4 weeks [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]


Enrollment:	68
Study Start Date:	January 2004
Study Completion Date:	February 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: pemetrexed + gemcitabine 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.	Drug: gemcitabine hydrochloride Drug: pemetrexed disodium

Detailed 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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059865

Show 41 Study Locations

Sponsors and Collaborators

Alliance for Clinical Trials in Oncology

National Cancer Institute (NCI)

Investigators


Study Chair:	Steven R. Alberts, MD	Mayo Clinic

More Information

Publications:

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 Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-149, 2007.

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 Gastrointest Cancer. 2007;38(2-4):87-94. doi: 10.1007/s12029-008-9037-8. Epub 2008 Nov 21.

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.


Responsible Party:	Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:	NCT00059865 History of Changes
Other Study ID Numbers:	N9943 NCCTG-N9943 CDR0000298862 NCI-2012-02530
Study First Received:	May 6, 2003
Last Updated:	August 11, 2016
Health Authority:	United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:


advanced adult primary liver cancer unresectable gallbladder cancer unresectable extrahepatic bile duct cancer adult primary cholangiocellular carcinoma

Additional relevant MeSH terms:


Liver Neoplasms Gallbladder Neoplasms Bile Duct Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Liver Diseases Biliary Tract Neoplasms Biliary Tract Diseases Gallbladder Diseases Bile Duct Diseases Gemcitabine	Pemetrexed Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016