Cetuximab and Radiation Therapy in Laryngeal Cancer Patients Who Have Responded to One Cycle of Chemotherapy (SPORE)
The purpose of this study is to learn how to identify early which patients will respond to chemotherapy plus radiation therapy in order to reduce the number of subjects who require surgery (followed by radiation therapy).
Cancer of Larynx
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Organ Preservation Trial Using Cetuximab and Radiation Therapy in Advanced Laryngeal Cancer Patients Who Have Responded to One Cycle of Induction Chemotherapy With Taxotere, Cisplatin, 5-Fluorouracil (TPF), and Cetuximab|
- Percentage of Patients Achieving Histologic Complete Response [ Time Frame: 3 years ] [ Designated as safety issue: No ]The proportion of patients treated with radiation+cetuximab achieving histologic CR will be estimated, along with 95% exact confidence intervals. Histologic Complete Response (CR) will be defined as primary tumors exhibiting a clinical CR or at least a 90% PR (Partial Response) along with a negative post-treatment biopsy.
- To Determine Tumor EGFR Degradation, as Well as Other Markers of Down-stream EGFR Inhibition, Observed in Tumor Biopsies Taken Shortly After the Administration of Cetuximab Following TPF, Compared With Pre-treatment Biopsies. [ Time Frame: 3 years. ] [ Designated as safety issue: No ]
- To Evaluate the Quality of Life (QOL). [ Time Frame: 3 years. ] [ Designated as safety issue: No ]
- To Determine the Overall Survival Rates Compared to the Overall Survival Rates of Historical Controls. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To Determine and Compare Toxicities, Most Notably Mucositis and Dysphagia, in Patients on This Treatment Regimen as Compared to Historical Controls. [ Time Frame: 3 years. ] [ Designated as safety issue: No ]
|Study Start Date:||August 2007|
|Study Completion Date:||October 2010|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
Patients will undergo induction chemotherapy with (TPF): Docetaxel (Taxotere) 75 mg/m2 and cisplatin 100 mg/m2 on day 1, and 5-FU 750 mg/m2 days 1-4.
On day 20 patients will receive a single dose of cetuximab (C-225) 400 mg/m2.
Depending upon disease response, patients will undergo salvage laryngectomy followed by radiation therapy and chemotherapy.
1. Day 1: 100 mg/m2, administered as an i.v. infusion will run over one hour. 2. Day #23: Subjects with a < 50% response (NR) to induction chemotherapy will undergo salvage laryngectomy followed by RT. Cisplatin will be added to radiation for patients whose surgical pathology reveals high-risk features (i.e. extracapsular spread, > 2 positive lymph nodes, perineural invasion, or positive margins). Cisplatin will either be dosed a 100 mg/m2 every 21 days or 40 mg/m2 weekly at the discretion of the prescribing physician.
Other Name: Platinol®-AQDrug: Cetuximab
1. Cetuximab will be administered at 400 mg/m2 on Day 20 (2 hour administration). 2. Cetuximab will be administered in combination with radiation therapy to those subjects who had a Partial or Complete response after the first cycle of the chemotherapy regimen is administered. The dosage for these administrations is 250 mg/m2 over sixty minutes and it will be administered for six weeks.
Other Names:Drug: 5-Fluorouracil
5-FU will be administered 750 mg/m2 in 0.9% normal saline as a 24-hour continuous infusion, days #1-4.
Other Names:Drug: Docetaxel
75 mg/m2 by I.V. over one hour on Day # 1 only
Other Name: Taxotere®
In this study one cycle of chemotherapy will be administered and then those subjects who respond well to that cycle will be started on radiation therapy along with chemotherapy and those that don't respond well to the initial cycle of chemotherapy, will undergo a total laryngectomy (surgery to remove the voice box) followed by radiation therapy. The initial cycle of chemotherapy consists of the drugs Taxotere, Cisplatin, and 5-Fluorouracil (this combination is known as TPF). Then on Day 20 of the study, the subjects will be administered another chemotherapy agent called cetuximab (a.k.a. C-225). It will then be determined if the patient's response to the chemotherapy was favorable by examining the patient's tumor with an endoscopy. If the response is determined to be good, then the patient will continue with a chemotherapy regimen with the addition of radiation therapy combination. If the patient's response to the chemotherapy is determined to be less than favorable, then the patient will be advised to undergo salvage surgery (a.k.a. laryngectomy) to remove their voice box and then undergo radiation therapy treatment. Additionally, tumor tissue samples and blood will be studied to see if there are special molecular markers that help predict when a tumor will respond to chemotherapy and radiation treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00599131
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109-0848|
|Principal Investigator:||Francis P. Worden, M.D.||University of Michigan|