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

This study has been terminated.
(The study was discontinued prematurely due to early stopping rules.)
Sponsor:
Information provided by (Responsible Party):
Francis (Frank) Worden, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00599131
First received: December 12, 2007
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Cancer of Larynx
Drug: Cisplatin
Drug: Cetuximab
Drug: 5-Fluorouracil
Drug: Docetaxel
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 4
Study Start Date: August 2007
Study Completion Date: October 2010
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: 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.
Other Name: Platinol®-AQ
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.
Other Names:
  • C-225
  • Erbitux®
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:
  • Adrucil®
  • Carac™
  • Efudex®
  • Fluoroplex®
  • 5-FU
  • FU
Drug: Docetaxel
75 mg/m2 by I.V. over one hour on Day # 1 only
Other Name: Taxotere®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00599131

Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0848
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Francis P. Worden, M.D. University of Michigan
  More Information

No publications provided

Responsible Party: Francis (Frank) Worden, Associate Professor of Internal Medicine, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00599131     History of Changes
Other Study ID Numbers: UMCC 2007.029, HUM 11350
Study First Received: December 12, 2007
Results First Received: April 16, 2014
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:
Cancer of Larynx

Additional relevant MeSH terms:
Laryngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Docetaxel
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 27, 2014