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

Alternate Title

Erlotinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Mouth or Throat Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI JHOC-20020723 JHOC-J0174, NCI-5375, 5375, NCT00049166

Objectives

1. Determine the maximum tolerated dose of erlotinib administered with intensity-modulated radiotherapy (IMRT) with or without cisplatin in patients with stage II, III, or IV squamous cell carcinoma of the oral cavity or oropharynx.
2. Determine the safety of these regimens in these patients.
3. Determine biological markers of activity of erlotinib in tumor biopsy specimens from these patients before and after treatment with these regimens.
4. Determine the ability of fludeoxyglucose F 18 positron-emission tomography scan to demonstrate biological activity of erlotinib and predict clinical response in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed squamous cell carcinoma of the oral cavity (OC) or oropharynx (OP)
  • OC sites include: oral tongue, buccal mucosa, floor of mouth, retromolar trigone, alveolar ridge, hard palate, and mucosal lip
  • OP sites include: base of tongue, tonsil, soft palate, and oropharyngeal wall
  • Stage II (T2, N0) or III (T1-2, N1) (eligible for regimen A only)
  • Stage III (T3, N0-1) or IV (T1-4, N2-3, M0 or T4, N0-1, M0) (eligible for regimen B only)



• Documentation of evaluable tumor within the past 4 weeks



• Operable or inoperable tumors allowed



• No known brain involvement



• No prior head and neck malignancies

Prior/Concurrent Therapy:

Biologic therapy

• No prior immunotherapy for this malignancy

Chemotherapy

• No prior chemotherapy for this malignancy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this malignancy

Surgery

• No prior surgical procedures affecting absorption
• At least 28 days since prior major surgery

Other

• No prior epidermal growth factor receptor-targeting therapies for this malignancy
• No prior investigational agents for this malignancy
• No other prior therapy for this malignancy
• No concurrent commercial or other investigational anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent warfarin

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• At least 6 months

Hematopoietic

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

Hepatic

• Bilirubin normal (unless due to hemolysis or Gilbert's syndrome)
• AST/ALT no greater than 2.5 times upper limit of normal
• aPTT/INR normal (correctable with vitamin K)

Renal

• Creatinine normal

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No untreated or new cardiac arrhythmia

Ophthalmic

• No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
• No congenital abnormalities (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 (e.g., Schirmer test or similar tear production test)

Gastrointestinal

• G-tube dependency allowed
• No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
• No active peptic ulcer disease
• No known malabsorption syndrome

Other

• No other concurrent uncontrolled illness that would preclude study participation
• No ongoing or active infection
• No uncontrolled diabetes mellitus
• No psychiatric illness or social situation that would preclude study participation
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib or other study agents
• No significant traumatic injury within the past 28 days
• No other malignancy within the past 3 years except completely resected basal cell skin cancer or carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 24-48 patients (12-24 per regimen) will be accrued for this study within 6-24 months.

Outline

This is a multicenter, dose-escalation study of erlotinib. Patients are assigned to 1 of 2 regimens according to disease stage.

• Regimen A (patients with stage II [T2, N0] or III [T1-2, N1] disease): Patients receive oral erlotinib once daily. Beginning on day 15, patients also undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 7 weeks.



• Regimen B (patients with stage III [T3, N0-1] or IV [T1-4, N2-3, M0 or T4, N0-1, M0] disease): Patients receive oral erlotinib and undergo IMRT as in regimen A. Patients also receive cisplatin IV over 20 minutes on each day of radiotherapy.

Patients in both regimens continue to receive erlotinib until the last day of IMRT (patients already in the maintenance phase of this study as of 5/11/04 continue to receive erlotinib once daily for up to 2 years) in the absence of disease progression or unacceptable toxicity.

In both regimens, 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 30 days and then every 3 months for up to 2 years.

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Maura Gillison, MD, PhD, Protocol chair		Ph: 410-502-7412

Registry Information
Official Title		A Phase I Study Of OSI-774 In Combination With Intensity-Modulated Radiation (IMRT) Therapy In Patients With Oral Cavity Or Oropharyngeal Cancer Stage II Or III And In Combination With Standard Fractionation Radiation Therapy And Low Dose Daily Cisplatin In Patients With Oral Cavity Or Oropharyngeal Cancer Stage III And IV
Trial Start Date		2002-11-11
Registered in ClinicalTrials.gov		NCT00049166
Date Submitted to PDQ		2002-09-05
Information Last Verified		2007-06-14
NCI Grant/Contract Number		CA70095, CA06973

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