Study Using Pharmacogenetics to Select Treatment for Head and Neck Cancer

Phase 2

Withdrawn

• Conditions: Head and Neck Cancer
• Interventions: Drug: Cetuximab; Drug: Cisplatin

• Registration Number: NCT00881114
• Lead Sponsor: Georgetown University

Brief Summary

This is a study for patients with head and neck cancer who will be receiving chemotherapy and radiation therapy for their disease. The purpose of this study is to see if the investigators can use genetic differences between patients to select the right drug to use with radiation therapy. This type of genetic testing is called pharmacogenetics.

Currently there are two drugs used to treat head and neck cancer that have provided a benefit when given with radiation compared to radiation alone in previous studies. These two drugs are cisplatin and cetuximab (Erbitux).

In this trial, the investigators will test whether genetic differences between patients can be used to pick which drug they should receive. A recent study that looked back to see how well patients with head and neck cancer responded to treatment with cisplatin showed that genetic differences in a few genes were associated with who did and who did not survive their cancer. The investigators are taking that finding and using it to test patients for these genetic differences to determine whether they should receive cisplatin or cetuximab. In other words, the investigators are trying to take what is essentially a flip of the coin choice between these two drugs, and instead use individual patient's genetic differences to make-and hopefully improve- this choice.

Detailed Description

Treatment-naive patients with locally advanced, non-metastatic (Stage III to IVB) squamous cell carcinoma of the head and neck who are candidates for concurrent chemoradiotherapy as primary therapy with curative intent will be enrolled. Patients will be genotyped for variations at four SNP loci in 3 genes involved in DNA nucleotide excision repair (ERCC1, ERCC2, and XRCC1). Patients with 3 to 8 variants will receive cisplatin, while patients with 2 or fewer variants will receive cetuximab.

Study Timeline

• Status Verified: 2009-04
• Study Start: 2009-04
• Study First Submitted: 2009-04-13
• Study First Submitted QC: 2009-04-14
• Study First Posted: 2009-04-15
• Primary Completion: 2009-06
• Study Completion: 2013-06
• Last Update Submitted: 2015-03-26
• Last Update Posted: 2015-03-27

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Biopsy proven squamous cell carcinoma of the head and neck, including of the oral cavity, oropharynx, hypopharynx, or larynx
• Locally advanced, Stage III or IVB disease and a candidate for primary therapy using chemotherapy and radiation with curative intent
• Patients with a diagnosis of 'unknown primary' will be eligible if chemoradiotherapy is primary modality of treatment
• No previous chemotherapy, radiation, or surgery for the diagnosis of head and neck cancer
• ECOG performance status 0 or 1
• Negative pregnancy test
• Hemoglobin >/= 8.0
• Absolute neutrophil count >/= 1500
• Platelet count >/= 100,000
• GFR > 50 mL/min
• Total bilirubin </= 1.5 upper limits of normal
• AST and ALT </= 2.5 times upper limits of normal
• No other current malignancy, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular in situ of the breast.
• Ability and willingness to give consent
• Subjects must in the opinion of the Investigator be capable of complying with the protocol

Exclusion Criteria

• Primary tumors of the nasopharynx, sinuses, and salivary glands
• Acute treatment for an infection or other serious medical illness within 14 days prior to study entry
• Major surgery within 3 weeks prior to study entry
• Known hypersensitivity to cisplatin or cetuximab
• Patients who have any severe or uncontrolled medical conditions or other conditions that could affect their participation in this study including: unstable angina, serious uncontrolled cardiac arrhythmia, active or uncontrolled infectious disorder, myocardial infarction </= 6 months prior to study entry
• Psychiatric illness that would limit compliance with study requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cetuximab	Cetuximab	patients with 2 or fewer genetic variants will receive cetuximab
Cisplatin	Cisplatin	Subjects with 3 to 8 genetic variants will receive cisplatin

Primary Outcome Measures

Name	Time	Method
Progression-free survival	36months

Secondary Outcome Measures

Name	Time	Method
Objective response	36 months
Overall survival	36 months
Toxicity	8 weeks
Quality of Life	36 months