Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI MSKCC-03031 NCI-5441, NCT00063947, 5441

Objectives

1. Determine the maximum tolerated dose of erlotinib given concurrently with gemcitabine and radiotherapy in patients with locally advanced unresectable pancreatic cancer.
2. Determine the toxicity of this regimen in these patients.
3. Determine, preliminarily, the antitumor efficacy of this regimen, in terms of response rate, in these patients.
4. Determine the time to tumor progression and overall survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
  • Locally advanced, unresectable disease, defined by all of the following:
    • Obvious encasement of the celiac, hepatic, or superior mesenteric artery
    • Encasement of the portal or superior mesenteric vein not amenable to surgical resection
    • Extrapancreatic extension with or without regional lymph node involvement
    • No evidence of distant metastatic disease by staging laparoscopy*

     [Note: *Patients determined to be unsuitable for this procedure (e.g., prior abdominal surgery, adhesions, etc.) by a surgeon are allowed to participate provided all other eligibility criteria are met]

  • Locally recurrent disease after prior curative surgery allowed provided the following are true:
    • No prior chemotherapy or radiotherapy
    • No evidence of distant metastatic disease by staging laparoscopy*

   [Note: *Patients determined to be unsuitable for this procedure (e.g., prior abdominal surgery, adhesions, etc.) by a surgeon are allowed to participate provided all other eligibility criteria are met]




• No islet cell pancreatic cancer or lymphoma or sarcoma of the pancreas



• Measurable or evaluable disease
  • Primary pancreatic tumor is considered evaluable and not measurable disease
  • Lymph node mass considered measurable disease



• No known brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior gemcitabine

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics

Other

• No prior epidermal growth factor receptor-targeting therapy
• No prior therapy for pancreatic cancer (except surgery)
• No concurrent commercial or other investigational agents or therapies intended to treat the malignancy
• No concurrent combination antiretroviral therapy for HIV-positive patients

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Creatinine ≤ 2.0 mg/dL

  OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Ophthalmic

• No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's syndrome)
• No congenital abnormality (e.g., Fuch's dystrophy)
• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• No abnormal corneal sensitivity test (Schirmer test or similar tear production test)

Gastrointestinal

• No Crohn's disease or inflammatory bowel disease that would preclude undergoing external beam radiotherapy
• Able to tolerate oral medication
• No requirement for IV alimentation

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

A total of 19-28 patients will be accrued for this study.

Outcomes

Maximum tolerated dose of erlotinib

Toxicity as measured by NCI Common Toxicity Criteria
Antitumor efficacy (response rate) by WHO criteria

Outline

This is a non-randomized, open-label, dose-escalation study of erlotinib.

• Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30 minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients receive treatment at that dose.

  Patients are radiologically restaged 3-4 weeks after completion of radiotherapy. Patients with stable or responsive disease proceed to maintenance therapy. Patients whose imaging studies suggest a potential for curative resection are referred for a surgical evaluation before initiating maintenance therapy.




• Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Eileen O'Reilly, MD, Protocol chair		Ph: 212-639-6672; 800-525-2225 Email: oreillye@mskcc.org

Registry Information
Official Title		A Phase I Study Of OSI-774 In Combination With Gemcitabine And Radiation In Locally Advanced, Non-Operable Pancreatic Cancer
Trial Start Date		2003-06-23
Registered in ClinicalTrials.gov		NCT00063947
Date Submitted to PDQ		2003-05-13
Information Last Verified		2006-11-16
NCI Grant/Contract Number		CA08748, CA69856

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