Study Using Pharmacogenetics to Select Treatment for Head and Neck Cancer (PGx-SELECT)

This study has been withdrawn prior to enrollment.
(Investigator decided it was not feasible to conduct this study)
Sponsor:
Information provided by:
Georgetown University
ClinicalTrials.gov Identifier:
NCT00881114
First received: April 13, 2009
Last updated: August 18, 2009
Last verified: April 2009
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: Cisplatin
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Phase II Clinical Trial to Use Pharmacogenetics (PGx) to Select Erbitux or Cisplatin to Treat Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 36months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Quality of Life [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 96
Study Start Date: April 2009
Estimated Study Completion Date: June 2013
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab
patients with 2 or fewer genetic variants will receive cetuximab
Drug: Cetuximab
Intensity modulated Radiation Therapy with concurrent chemotherapy. Cetuximab will be administered beginning at a dose of 400 mg/m2 the week before radiation commences, then at a dose of 250 mg/m2 weekly during weeks 1 to 7. Post treatment neck dissection will be performed if clinically indicated.
Other Name: Erbitux
Experimental: Cisplatin
Subjects with 3 to 8 genetic variants will receive cisplatin
Drug: Cisplatin
Intensity modulated radiation therapy with concurrent chemotherapy. Cisplatin will be administered at a dose of 100 mg/m2 during weeks 1, 4, and 7 of radiation therapy. Post treatment neck dissection will be performed if clinically indicated.
Other Names:
  • cis-diamminedichloridoplatinum(II)
  • CDDP

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00881114

Sponsors and Collaborators
Georgetown University
Investigators
Principal Investigator: John Deeken, MD Georgetown University
  More Information

No publications provided

Responsible Party: John Deeken, MD, Georgetown University Medical Center
ClinicalTrials.gov Identifier: NCT00881114     History of Changes
Other Study ID Numbers: PGx-SELECT, 2008-526
Study First Received: April 13, 2009
Last Updated: August 18, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Georgetown University:
Head and neck cancer
pharmacogenetics
chemoradiotherapy

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 19, 2014