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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2; Phase 1

Conditions: Gallbladder Cancer; Extrahepatic Bile Duct Cancer; Liver Cancer

Treatments: Drug: pemetrexed disodium; Drug: gemcitabine hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00059865

N9943

CDR0000298862 (Registry Identifier)

NCI-2012-02530 (Registry Identifier)

NCCTG-N9943

Details and patient eligibility

About

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.

Full 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.

Enrollment: 68 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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68 participants in 1 patient group

pemetrexed + gemcitabine

Experimental group

Description:

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.

Treatment:

Drug: gemcitabine hydrochloride

Drug: pemetrexed disodium