Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI NCCTG-N9943 N9943, NCT00059865

Objectives

1. 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.)
2. Determine the 6-month survival rate of patients treated with this regimen.
3. Determine the best objective tumor response rate and duration of best objective tumor response in patients treated with this regimen.
4. Determine the time to progression and overall survival of patients treated with this regimen.
5. Determine the toxic effects of this regimen in these patients.
6. 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.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• 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

Chemotherapy

• 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

Endocrine therapy

• Not specified

Radiotherapy

• 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

Surgery

• Not specified

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• AST no greater than 5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

  OR

• Creatinine clearance at least 45 mL/min

Other

• 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

Expected Enrollment

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

Outcomes

Survival after 6 months of treatment

Response as assessed by RECIST criteria every 8-16 weeks
Toxicity as assessed by CTC v3 every 4 weeks

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.

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.

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.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Steven Alberts, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Registry Information
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
Trial Start Date		2004-01-14
Trial Completion Date		2008-02-27
Registered in ClinicalTrials.gov		NCT00059865
Date Submitted to PDQ		2003-03-11
Information Last Verified		2007-07-21
NCI Grant/Contract Number		CA25224