Pemetrexed Disodium and Gemcitabine in Treating Patients With Advanced Cancer of the Urothelium

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 2

Conditions: Transitional Cell Cancer of the Renal Pelvis and Ureter; Bladder Cancer; Urethral Cancer

Treatments: Drug: pemetrexed disodium; Drug: gemcitabine hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00053209

ECOG-E4802

CDR0000269302

Details and patient eligibility

About

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

PURPOSE: Phase II trial to study the effectiveness of combining pemetrexed disodium with gemcitabine in treating patients who have advanced cancer of the urothelium.

Full description

OBJECTIVES:

Primary

• Determine the response rate in patients with previously untreated advanced cancer of the urothelium treated with pemetrexed disodium and gemcitabine.
• Determine the toxicity of this regimen in these patients.

Secondary

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

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Patients also receive cyanocobalamin intramuscularly once every 9 weeks and folic acid orally once daily beginning on day -6 and continuing until 3 weeks after the completion of study therapy. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 24-46 patients will be accrued for this study within 15 -18 months.

Enrollment: 46 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed cancer of the urothelium (renal pelvis, ureter, bladder, or urethra)

  • Any of the following types:

    • Transitional cell carcinoma (TCC)
    • Mixed histologies containing a component of TCC
    • Non-TCC of the urothelium (renal pelvis, ureter, bladder, or urethra)

• Progressing regional or metastatic disease

• Measurable disease

• No clinical evidence of CNS metastases

• No evidence of clinically significant (by physical exam or plain film) third-space fluid collections (pleural effusions or ascites)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• AST no greater than 3 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN

Renal

• Creatinine clearance at least 45 mL/min

Cardiovascular

• No history of severe cardiovascular disease (i.e., American Heart Association class III or IV heart disease)
• No uncontrolled congestive heart failure
• No ventricular dysrhythmias

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No active unresolved infection
• No other prior malignancy unless curatively treated and disease free for an appropriate (disease-specific) period of time
• Able and willing to receive folic acid and cyanocobalamin supplementation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior systemic biologic response modifier therapy

Chemotherapy

• No prior systemic chemotherapy for metastatic disease
• More than 1 year since prior neoadjuvant or adjuvant chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No prior pelvic radiotherapy
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior major surgery and recovered

Other

• More than 7 days since prior parenteral antibiotics
• No salicylates for 2 days before, during, and for 2 days after administration of pemetrexed disodium
• No nonsteroidal anti-inflammatory drugs for at least 5 days before, during, and for 2 days after administration of pemetrexed disodium

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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46 participants in 1 patient group

Pemetrexed Disodium and Gemcitabine

Experimental group

Description:

Pemetrexed disodium 500 mg/m2 followed by gemcitabine 1000 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on day 8 of a 21-day cycle for a maximum of 6 cycles

Treatment:

Drug: pemetrexed disodium

Drug: gemcitabine hydrochloride