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

Sponsor

University Health Network, Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT00030576

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Actual Duration (Months)

8.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with cisplatin may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining erlotinib and cisplatin in treating patients who have recurrent or metastatic head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: cisplatin Drug: erlotinib hydrochloride	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the objective response rate in patients with recurrent or metastatic squamous cell cancer of the head and neck treated with erlotinib and cisplatin.
Determine the stable disease rates, duration of response, progression-free survival, median survival, and overall survival of patients treated with this regimen.
Determine the safety and tolerability of this regimen in these patients.
Determine the relationship between clinical, pharmacokinetic, and pharmacodynamic effects of this regimen in these patients.
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.

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 1, 2001

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OSI-774 and cisplatin HNSCC patients treated in three escalating dose cohorts of daily continous oral erlotinib (OSI-774) and intermittent IV cisplatin given every 21 days	Drug: cisplatin Drug: erlotinib hydrochloride

Arm

Intervention/Treatment

Experimental: OSI-774 and cisplatin

HNSCC patients treated in three escalating dose cohorts of daily continous oral erlotinib (OSI-774) and intermittent IV cisplatin given every 21 days

Drug: cisplatin

Drug: erlotinib hydrochloride

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
2	Queen's University	Kingston	Ontario	Canada	K7L 3N6
3	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
4	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K1H 1C4
5	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
6	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2L-4M1

Sponsors and Collaborators

University Health Network, Toronto
National Cancer Institute (NCI)

Investigators

Study Chair: Lillian L. Siu, MD, FRCPC, Princess Margaret Hospital, Canada
Study Chair: Elizabeth A. Eisenhauer, MD, Cancer Research Institute at Queen's University