Pemetrexed, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer

Wake Forest University (WFU)

Status and phase

Terminated

Phase 1

Conditions

Pancreatic Cancer

Treatments

Device: Radiotherapy

Drug: pemetrexed disodium

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00310050

LILLY-H3E-US-X031

CCCWFU-BG04-529

CCCWFU-57103

CDR0000466320

Details and patient eligibility

About

RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of pemetrexed when given together with radiation therapy in treating patients with locally advanced pancreatic cancer.

Full description

OBJECTIVES:

Primary

Determine the maximum tolerated dose of pemetrexed disodium when given in combination with upper abdominal radiotherapy after induction therapy comprising gemcitabine hydrochloride and pemetrexed disodium followed by consolidation therapy with gemcitabine hydrochloride in patients with locally advanced pancreatic cancer.
Determine the quantitative toxicity of this regimen in these patients.

Secondary

Determine the quantitative and qualitative dose-limiting toxicities of pemetrexed disodium in combination with upper abdominal radiation therapy.
Evaluate patterns of failure, response, and survival of these patients at 1 year

OUTLINE: This is an open-label, nonrandomized, dose-escalation study of pemetrexed disodium.

Induction therapy: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 14 days for 3 courses. Approximately 2 weeks later, patients without disease progression proceed to chemoradiotherapy.
Chemoradiotherapy: Patients receive pemetrexed disodium IV over 10 minutes on days 1, 15, and 29 and undergo radiotherapy once daily 5 days a week for 5 ½ weeks. Approximately 2-3 weeks later, patients without disease progression proceed to consolidation therapy.

Cohorts of 3-9 patients receive escalating doses of pemetrexed disodium during chemoradiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which ≤ 20% or ≤ 2 of 9 patients experience dose-limiting toxicity.

Consolidation therapy: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Enrollment

4 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed carcinoma arising from the pancreas
- Stage II or III disease, meeting 1 of the following criteria:
  - Nonresectable disease
  - Potentially resectable disease
  - Resectable disease
- Stage IV disease with symptomatic back pain requiring palliation allowed at the discretion of the principal investigator
Measurable, evaluable, or nonmeasurable disease
No neuroendocrine tumor of the pancreas
No documented brain metastasis
No clinically significant pleural or peritoneal effusions that cannot be drained

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy ≥ 12 weeks
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 3 times ULN (5 times ULN if liver has tumor involvement)
AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement)
Creatinine clearance ≥ 45 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No active infection
No serious systemic disorders that would preclude study treatment
No significant cardiovascular disease in the form of abnormal electrocardiogram coupled with clinical features of recent or recurrent cardiac disease (including myocardial infarction, angina, or hypertension)

PRIOR CONCURRENT THERAPY:

More than 4 weeks since prior investigational agents
No prior chemotherapy for pancreatic cancer
Must be able to discontinue aspirin, dexamethasone, and other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after pemetrexed disodium dose (5 days before for long-acting agents such as piroxicam)
Must be able and willing to take folic acid and cyanocobalamin (vitamin B12) supplementation