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

• ClinicalTrials.gov Identifier: NCT00310050
• Recruitment Status: Terminated
• First Posted: April 3, 2006
• Results First Posted: November 30, 2018
• Last Update Posted: November 30, 2018
• Sponsor: Wake Forest University Health Sciences
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Study Description

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; Device: Radiotherapy	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: N/A
• 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

Arm

Intervention/treatment

Experimental: Pemetrexed in combination with concomitant radiotherapy; Patients will receive Pemetrexed plus Radiotherapy.

Drug: pemetrexed disodium; 500 milligrams per meter squared day will be given during weeks 1, 3 and 5 of the radiation (3 total doses of Pemetrexed during the radiation therapy).; Device: Radiotherapy; During the chemoradiation, the radiotherapy will be administered in 1.8 Gy/fractions after completion of the Pemetrexed infusion, and continue daily (Monday through Friday) for 5 1/2 weeks for a total delivered dose of 50.4 Gy (Total of 28 radiation treatments).

Outcome Measures

Primary Outcome Measures :

1. Determine Maximum Tolerated Dose of Pemetrexed When Administered With Concomitant Radiation Therapy [ Time Frame: 42 days ]
2. Quantitative Toxicity of Pemetrexed When Administered With Concomitant Radiation Therapy [ Time Frame: 42 days ]

Secondary Outcome Measures :

1. Qualitative Dose-limiting Toxicities of Pemetrexed in Combination With Radiation Therapy [ Time Frame: 42 days ]
   Toxicity will be determined using the revised NCI Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting. Number of events with grade 1-5 will be reported.
2. Patterns of Failure [ Time Frame: 1 year ]
3. Patterns of Response [ Time Frame: 1 year ]
4. Number of Participants That Survived [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• 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

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

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00310050
• Other Study ID Numbers: CDR0000466320; CCCWFU-57103; LILLY-H3E-US-X031; CCCWFU-BG04-529
• First Posted: April 3, 2006
• Results First Posted: November 30, 2018
• Last Update Posted: November 30, 2018
• Last Verified: November 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

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; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors