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

Alternate Title

Erlotinib and Cisplatin in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI PMH-PHL-002 NCI-5380, CAN-NCIC-IND157, 5380, NCT00030576, IND157

Objectives

1. Determine the objective response rate in patients with recurrent or metastatic squamous cell cancer of the head and neck treated with erlotinib and cisplatin.
2. Determine the stable disease rates, duration of response, progression-free survival, median survival, and overall survival of patients treated with this regimen.
3. Determine the safety and tolerability of this regimen in these patients.
4. Determine the relationship between clinical, pharmacokinetic, and pharmacodynamic effects of this regimen in these patients.
5. Correlate baseline and post-treatment levels of epidermal growth factor receptor, its downstream signaling components, and markers of angiogenesis and apoptosis in tumor and skin biopsies with clinical outcome in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed squamous cell carcinoma of the head and neck
  • All primary sites, including oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, and paranasal sinus



• Recurrent, unresectable, and/or metastatic disease



• At least 1 measurable lesion
  • At least 20 mm with conventional techniques OR at least 10 mm with spiral CT scan



• Lesions accessible for biopsy



• Tumor specimen available for evaluation of epidermal growth factor receptor (EGFR) expression



• No known brain metastases

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for recurrent or metastatic disease
• Prior platinum-based chemotherapy with radiotherapy or platinum-based induction chemotherapy allowed
• At least 6 months since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Chemotherapy
• At least 4 weeks since prior radiotherapy (except low-dose, limited-fraction palliative non-myelosuppressive radiotherapy [e.g., involving less than 20% of functioning bone marrow using 800 cGy in 1 fraction or 2,000 cGy in 5 fractions]) and recovered
• No prior radiotherapy to target lesion unless there is evidence of disease progression

Surgery:

• See Disease Characteristics
• At least 21 days since prior major surgery
• No prior surgical procedure affecting gastrointestinal absorption

Other:

• No prior EGFR-targeting therapies
• No prior investigational agents for recurrent or metastatic disease
• No concurrent combination anti-retroviral therapy for HIV infection
• No other concurrent investigational agents
• No other concurrent anticancer treatment

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy:

• More than 12 weeks

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN

Renal:

• Creatinine normal

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

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

Gastrointestinal:

• No gastrointestinal tract disease resulting in malabsorption
• No requirement for IV alimentation
• No active peptic ulcer disease
• Inability to swallow tablets or silicon-based G-tubes allowed

Ophthalmic:

• No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjogren'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 (e.g., Schirmer test or similar tear production test)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except carcinoma in situ of the cervix, nonmelanoma skin cancer, or second primary squamous cell cancer originating from the head and neck
• No grade 2 or greater residual ototoxicity or neuropathy from prior platinum-based therapy
• No significant traumatic injury within the past 21 days
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation

Expected Enrollment

A maximum of 43 patients will be accrued for this study within 18 months.

Outline

This is a dose-escalation, multicenter study.

Patients receive oral erlotinib once daily on days -6 to 21 for the first course only and cisplatin IV over 60 minutes on day 1. For the second and subsequent courses, patients receive oral erlotinib once daily on days 1-21 and cisplatin as in course 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after 6 courses may continue to receive erlotinib alone until disease progression.

Cohorts of 3-6 patients receive escalating doses of erlotinib and cisplatin 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. At least 6 patients are treated at the MTD.

Patients are followed every 3 months.

Agulnik M, da Cunha Santos G, Hedley D, et al.: Predictive and pharmacodynamic biomarker studies in tumor and skin tissue samples of patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with erlotinib. J Clin Oncol 25 (16): 2184-90, 2007.[PUBMED Abstract]

Siu LL, Soulieres D, Chen EX, et al.: Phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Princess Margaret Hospital phase II consortium and National Cancer Institute of Canada Clinical Trials Group Study. J Clin Oncol 25 (16): 2178-83, 2007.[PUBMED Abstract]

Winquist E, Soulieres D, Chen E, et al.: A phase II study of erlotinib in combination with cisplatin in patients with recurrent or metastatic squamous cell cancer of the head and neck (PHL002es/NCIC CTG IND.157). [Abstract] Eur J Cancer 2 (Suppl 8): A-408, 122, 2004.

Siu LL, Chen X, Tsao M: A phase I/II study of erlotinib (Tarceva) in combination with cisplatin in patients with recurrent or metastatic squamous cell cancer of the head and neck (HNSCC). [Abstract] Clin Cancer Res 9 (16): A-A92, 2003.

Trial Contact Information

Trial Lead Organizations

Princess Margaret Hospital

Lillian Siu, MD, FRCPC, Protocol chair		Ph: 416-946-2911

NCIC-Clinical Trials Group

Elizabeth Eisenhauer, MD, Protocol chair		Ph: 613-533-6430 Email: eeisenhauer@ctg.queensu.ca

Registry Information
Official Title		A Phase I/II Study Of OSI-774 In Combination With Cisplatin In Patients With Recurrent Or Metastatic Squamous Cell Cancer Of The Head And Neck
Trial Start Date		2001-11-19
Registered in ClinicalTrials.gov		NCT00030576
Date Submitted to PDQ		2001-12-05
Information Last Verified		2004-10-18
NCI Grant/Contract Number		CM17107

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