Clinical trial NCT00881114: Study Using Pharmacogenetics to Select Treatment for Head and Neck Cancer
Official title: A Prospective Phase II Clinical Trial to Use Pharmacogenetics (PGx) to Select Erbitux or Cisplatin to Treat Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: Head and neck cancer
pharmacogenetics
chemoradiotherapy
Lead sponsor: Georgetown University
Sponsor class: OTHER
First posted: 2009-04-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival
timeFrame: 36months
Secondary outcomes:
measure: Objective response
timeFrame: 36 months
measure: Overall survival
timeFrame: 36 months
measure: Toxicity
timeFrame: 8 weeks
measure: Quality of Life
timeFrame: 36 months
Other outcomes:
Locations:
Study officials:
affiliation: Georgetown University
name: John Deeken, MD
role: PRINCIPAL_INVESTIGATOR
References: