Cetuximab and Radiation Therapy in Laryngeal Cancer Patients Who Have Responded to One Cycle of Chemotherapy (SPORE)

NCT ID: NCT00599131

Last Updated: 2015-12-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2010-10-31

Brief Summary

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).

Detailed Description

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.

Conditions

Cancer of Larynx

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy/Radiation/Surgery

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.

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

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.

Cetuximab

Intervention Type: DRUG

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.

5-Fluorouracil

Intervention Type: DRUG

5-FU will be administered 750 mg/m2 in 0.9% normal saline as a 24-hour continuous infusion, days #1-4.

Docetaxel

Intervention Type: DRUG

75 mg/m2 by I.V. over one hour on Day # 1 only

Interventions

Cisplatin

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.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: DRUG

Docetaxel

75 mg/m2 by I.V. over one hour on Day # 1 only

Intervention Type: DRUG

Other Intervention Names

Platinol®-AQ; C-225; Erbitux®; Adrucil®; Carac™; Efudex®; Fluoroplex®; 5-FU; FU; Taxotere®

Eligibility Criteria

Inclusion Criteria

• Patients must have pathologically confirmed, previously untreated, resectable, squamous cell carcinoma of the larynx.
• Disease must be Stage III or IV.
• Tumor must be potentially surgically resectable and curable with conventional surgery and radiation therapy.
• Patients must undergo pre-treatment endoscopic tumor staging and CT scanning.
• ECOG Performance status 0-2
• Pre-treatment laboratory criteria:
• WBC > or = to 3500/ul, granulocyte > or = to 1500/ul.
• Platelet count > or equal to 100,000/ul.
• Calculated or measured creatinine clearance > or = to 60 cc/min.
• Total Bilirubin < or = to 1.5 X ULN.
• AST and ALT < or = to 2.5 X ULN.
• Patients must give documented informed consent to participate in this study.

Exclusion Criteria

• Prior head and neck malignancy or history of other prior non-head and neck malignancy within the past 3 years.
• Prior head and neck radiation or prior chemotherapy.
• Documented evidence of distant metastases.
• Active infection.
• Pregnancy or lactation. Patients must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after discontinuing therapy.
• Any medical or psychiatric illness which in the opinion of the principal investigator would compromise the patients ability to tolerate this treatment.
• Patients residing in prison.
• Age < 18 years.
• Patients with psychiatric/social situations that would limit compliance with study requirements are not eligible.
• Patients with prior radiation to the head and neck.
• Patients with prior anti-epidermal growth-factor receptor antibody therapy or therapy with a tyrosine-kinase inhibitor.
• Patients with Grade > 2 peripheral neuropathy.
• Any history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francis P. Worden, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

HUM 11350

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2007.029

Identifier Type: -

Identifier Source: org_study_id