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A Phase I Study of OSI-774 in Combination With Gemcitabine and Radiation in Locally Advanced, Non-Operable Pancreatic Cancer

Phase 1
18 Years
Not Enrolling
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer

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Trial Information

A Phase I Study of OSI-774 in Combination With Gemcitabine and Radiation in Locally Advanced, Non-Operable Pancreatic Cancer


I. Determine the maximum tolerated dose of erlotinib given concurrently with gemcitabine and
radiotherapy in patients with locally advanced unresectable pancreatic cancer.


I. Determine the toxicity of this regimen in these patients. II. Determine, preliminarily,
the antitumor efficacy of this regimen, in terms of response rate, in these patients.

III. Determine the time to tumor progression and overall survival of patients treated with
this regimen.

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.

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

Inclusion Criteria:

- 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*

- 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*

- 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

- Performance status - ECOG 0-2

- More than 12 weeks

- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1.5 mg/dL

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine ≤ 2.0 mg/dL

- Creatinine clearance ≥ 60 mL/min

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's

- No congenital abnormality (e.g., Fuch's dystrophy)

- No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or

- No abnormal corneal sensitivity test (Schirmer test or similar tear production test)

- 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

- 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

- See Disease Characteristics

- No prior gemcitabine

- See Disease Characteristics

- See Disease Characteristics

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (MTD) of erlotinib hydrochloride based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Outcome Time Frame:

7.5 weeks

Safety Issue:


Principal Investigator

Eileen O'Reilly

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2003

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Pancreas
  • Recurrent Pancreatic Cancer
  • Stage II Pancreatic Cancer
  • Stage III Pancreatic Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021