Pemetrexed, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer - Full Text View

Sponsors and Collaborators:	Wake Forest University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00310050

Purpose

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.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: gemcitabine hydrochloride Drug: pemetrexed disodium Radiation: radiation therapy	Phase I

MedlinePlus related topics: Cancer Pancreatic Cancer Radiation Therapy

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	A Phase I Dose-Escalating Study of Induction Gemcitabine/Pemetrexed Followed by Pemetrexed and Concurrent Upper Abdominal Radiation Therapy in Patients With Locally Advanced Pancreatic Cancer

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	33
Study Start Date:	October 2005
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310050

Locations

United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096

Sponsors and Collaborators

Wake Forest University

National Cancer Institute (NCI)

Investigators

Study Chair:

Arthur William Blackstock, MD

Wake Forest University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000466320, CCCWFU-57103, LILLY-H3E-US-X031, CCCWFU-BG04-529
Study First Received:	March 29, 2006
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00310050 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer

Study placed in the following topic categories:

Antimetabolites
Digestive System Neoplasms
Immunologic Factors
Pancreatic Neoplasms
Endocrine System Diseases
Folic Acid Antagonists
Antiviral Agents
Immunosuppressive Agents
Folic Acid

Pemetrexed
Digestive System Diseases
Radiation-Sensitizing Agents
Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Gemcitabine
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Digestive System Neoplasms
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Endocrine System Diseases
Enzyme Inhibitors
Folic Acid Antagonists

Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Pemetrexed
Neoplasms
Neoplasms by Site
Digestive System Diseases
Radiation-Sensitizing Agents
Therapeutic Uses
Pancreatic Diseases
Gemcitabine
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009