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

NCT00599131 | Terminated Phase 2 Results DMC

• 2 other identifiers: UMCC 2007.029HUM 11350
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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).

Conditions

Cancer of Larynx

Keywords

Cancer of Larynx

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Achieving Histologic Complete Response

  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.

  3 years

Secondary Outcomes (4)

• The Difference, From Baseline, in EGFR, for Tumor Biopsies Taken After the Administration of Cetuximab Following TPF.

  Day 23

• The Change in Overall Quality of Life Score During Radiation Therapy and at 6, 12, and 24 Months Post Treatment.

  24 months

• Overall Survival Time

  3 years

• The Number of Patients That Experience Grade 3 and 4 Mucositis or Dysphagia

  3 years.

Study Arms (1)

Chemotherapy/Radiation/Surgery

EXPERIMENTAL

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; Drug: Cetuximab; Drug: 5-Fluorouracil; Drug: Docetaxel

Interventions

Cisplatin 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.

Also known as: Platinol®-AQ

Chemotherapy/Radiation/Surgery

Cetuximab 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.

Also known as: C-225, Erbitux®

Chemotherapy/Radiation/Surgery

5-Fluorouracil DRUG

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

Also known as: Adrucil®, Carac™, Efudex®, Fluoroplex®, 5-FU, FU

Chemotherapy/Radiation/Surgery

Docetaxel DRUG

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

Also known as: Taxotere®

Chemotherapy/Radiation/Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0848, United States

Location

MeSH Terms

Conditions

Laryngeal Neoplasms

Interventions

Cisplatin; Cetuximab; Fluorouracil; Docetaxel

Condition Hierarchy (Ancestors)

Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The study was discontinued prematurely due to an early stopping rule.

Results Point of Contact

• Title: Dr. Francis Worden
• Organization: University of Michigan Comprehensive Cancer Center

fworden@umich.edu

734-936-0453

Study Officials

• Francis P. Worden, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2007
• First Posted: January 23, 2008
• Study Start: August 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: October 1, 2010
• Last Updated: December 3, 2015
• Results First Posted: June 16, 2014

Record last verified: 2015-11

Locations

US (1)