Use of Pharmacogenetics to Select Erbitux or Cisplatin to Treat Head and Neck Cancer

• Sponsor: Georgetown University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01790516
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 13
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is for patients with newly diagnosed head and neck cancer that cannot be removed by surgery.

The purpose of this study is to determine the feasibility of using genetic variations in patients to select the right drug to treat head and neck cancer. Cisplatin and cetuximab (Erbitux)are both approved by the FDA to treat head and neck cancer in combination with radiation therapy. In this study the investigators will test whether genetic differences between patients can be used to pick which of these two drugs a patient should receive. All patients will have a blood sample drawn that will be tested for genetic differences. If patients have genetic differences that correlate with a better outcome from cisplatin they will receive cisplatin with radiation. If patients have genetic differences that do not correlate with a better outcome from cisplatin they will receive cetuximab with their radiation therapy.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Cancer	Drug: Cisplatin; Drug: cetuximab; Radiation: Radiation	N/A

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 germline variations at four SNP loci in three genes involved in DNA nucleotide excision repair (ERCC1, ERCC2, and XRCC1). Patients with 3 to 8 variants will receive cisplatin (Arm A). Patients with 2 or fewer variants will receive cetuximab (Arm B).

The hypothesis of the study is that prospectively testing patients for variations in DNA repair enzymes to determine whether to use cisplatin or cetuximab in locally advanced head and neck squamous cell cancer is feasible.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Prospective Clinical Trial to Use Pharmacogenetics (PGx) to Select Erbitux or Cisplatin to Treat Head and Neck Cancer
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cisplatin Cisplatin	Drug: Cisplatin; Cisplatin 100 mg/m2 during weeks 1,4, and 7 of radiation therapy; Other Names: Cispaltin Platinum ; Radiation: Radiation; daily radiation for 7 weeks
Experimental: Cetuximab cetuximab	Drug: cetuximab; Cetuximab beginning at a dose of 400 mg/m2 the week before radiation commences and then 250 mg/m2 weekly during weeks 1 and 7 of radiation.; Other Names: Erbitux ; Radiation: Radiation; daily radiation for 7 weeks

Outcome Measures

Primary Outcome Measures

1. Feasibility of Returning Genetic Testing Results in a Timely Manner to the Treating Physician [20 months]

   Feasibility is defined as follows: - Patients' genetic test results are returned to the treating physician within 3 days

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Biopsy proven squamous cell carcinoma of the head and neck, including the oral cavity, oropharynx, hypopharynx, or larynx, but not including primary tumors of the nasopharynx, sinuses, or salivary glands.

• Locally advanced, Stage III to IVB disease, and a candidate for primary therapy using chemotherapy and radiation therapy with curative intent.

• Patients with a diagnosis of 'unknown primary' will be eligible if chemoradiotherapy is the primary modality of treatment

• No previous chemotherapy, radiation, or surgery for their diagnosis of head and neck cancer

• Eastern Cooperative Oncology Group performance status </= 1

• Women of child-bearing potential must have a negative pregnancy test within 30 hours before initiation of study drug dosing. Female subjects of reproductive potential must agree to avoid pregnancy throughout the study and for up to 3 months following discontinuation of study drug. Male subjects must agree to avoid conceiving a child throughout the study and for up to 3 months following discontinuation of study drug;

• Hemoglobin >/= 8.0 gm/dL

• Absolute neutrophil count >/= 1500

• Platelet count >/= 100,000

• Glomerular Filtration Rate > 50 mL/min calculated by the Cockcroft-Gault equation

• Total bilirubin </= 2.0 times the upper limit of normal unless the patient has Gilbert's syndrome

• Aspartate aminotransferase and Alanine Aminotransferase </= 2.5 times the upper limit 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. Patients with other malignancies are eligible if they have been continuously disease-free for

/= 3 years prior to screening for this protocol.

• Age of 18 or older

• Ability and willingness to give informed consent

• Subjects must in the opinion of the Investigator be capable of complying with this protocol.

Exclusion Criteria:

• 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 acute or uncontrolled infectious disorder, or myocardial infarction </= 6 months prior to study entry.

• Female patients who are pregnant or breast feeding, or adults who are of reproductive potential and are unwilling to refrain from conceiving a child during study treatment.

• Patients unwilling to comply with the protocol, or provide informed consent

• Psychiatric illness that would limit compliance with study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgetown Lombardi Comprhensive Cancer Center	Washington	District of Columbia	United States	20007

Sponsors and Collaborators

• Georgetown University

Investigators

• Principal Investigator: John F Deeken, MD, Georgetown University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Georgetown University
• ClinicalTrials.gov Identifier: NCT01790516
• Other Study ID Numbers: 2010-439
• First Posted: Feb 13, 2013
• Last Update Posted: Oct 2, 2014
• Last Verified: Oct 1, 2013

• Keywords provided by Georgetown University: Head and neck cancer; genetic testing; cisplatin; erbitux; radiation therapy
• Additional relevant MeSH terms: Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Cetuximab

Study Results

Participant Flow

Arm/Group Title	Cisplatin	Cetuximab
Arm/Group Description	Intensity modulated radiation with concurrent cisplatin platinum plus radiation: Cisplatin 100 mg/m2 during weeks 1,4, and 7 of radiation therapy	Intensity modulated radiation therapy with concurrent cetuximab cetuximab plus radiation therapy: Cetuximab beginning at a dose of 400 mg/m2 the week before radiation commences and then 250 mg/m2 weekly during weeks 1 and 7 of radiation.
Period Title: Overall Study
STARTED	1	1
COMPLETED	0	1
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Cisplatin	Cetuximab	Total
Arm/Group Description	Intensity modulated radiation with concurrent cisplatin platinum plus radiation: Cisplatin 100 mg/m2 during weeks 1,4, and 7 of radiation therapy	Intensity modulated radiation therapy with concurrent cetuximab cetuximab plus radiation therapy: Cetuximab beginning at a dose of 400 mg/m2 the week before radiation commences and then 250 mg/m2 weekly during weeks 1 and 7 of radiation.	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	1 100%	2 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility of Returning Genetic Testing Results in a Timely Manner to the Treating Physician
Description	Feasibility is defined as follows: - Patients' genetic test results are returned to the treating physician within 3 days
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cisplatin	Cetuximab
Arm/Group Description	Intensity modulated radiation with concurrent cisplatin platinum plus radiation: Cisplatin 100 mg/m2 during weeks 1,4, and 7 of radiation therapy	Intensity modulated radiation therapy with concurrent cetuximab cetuximab plus radiation therapy: Cetuximab beginning at a dose of 400 mg/m2 the week before radiation commences and then 250 mg/m2 weekly during weeks 1 and 7 of radiation.
Measure Participants	1	1
Median (Full Range) [days]	3	3

Adverse Events

Arm/Group Title	Cisplatin		Cetuximab
Arm/Group Description	Intensity modulated radiation with concurrent cisplatin platinum plus radiation: Cisplatin 100 mg/m2 during weeks 1,4, and 7 of radiation therapy		Intensity modulated radiation therapy with concurrent cetuximab cetuximab plus radiation therapy: Cetuximab beginning at a dose of 400 mg/m2 the week before radiation commences and then 250 mg/m2 weekly during weeks 1 and 7 of radiation.
All Cause Mortality
	Cisplatin		Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cisplatin		Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Cisplatin		Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.