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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Pancreatic Cancer	Drug: pemetrexed disodium	Phase 1

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	4 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Study Start Date :	October 2005
Actual Primary Completion Date :	May 2008
Actual Study Completion Date :	May 2008

Arms and Interventions

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Intervention Details:

Drug: pemetrexed disodium
500 milligrams per meter squared day 1,15,29 for 14 days for three cycles

Outcome Measures

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Primary Outcome Measures :

1. determine maximum tolerated dose of Premetrexed wehen given concurrently with gemcitabine [ Time Frame: 42 days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 120 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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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 Health Sciences

National Cancer Institute (NCI)

Investigators

Study Chair:	Arthur William Blackstock, MD	Wake Forest University Health Sciences

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:	NCT00310050 History of Changes
Other Study ID Numbers:	CDR0000466320; CCCWFU-57103; LILLY-H3E-US-X031; CCCWFU-BG04-529
First Posted:	April 3, 2006
Last Update Posted:	February 23, 2017
Last Verified:	February 2017

Keywords provided by Wake Forest University Health Sciences:

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

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Pemetrexed; Antimetabolites, Antineoplastic	Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors