Combination Chemotherapy Plus Radiation Therapy To Preserve the Larynx in Patients With Cancer of the Hypopharynx or Larynx

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00002839
First received: November 1, 1999
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells and allow doctors to preserve the part of the body where the cancer started. It is not yet known which regimen of cisplatin and fluorouracil combined with radiation therapy is more effective in treating resectable cancer of the hypopharynx or larynx.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of cisplatin and fluorouracil combined with radiation therapy in preserving the larynx in patients who have resectable cancer of the hypopharynx or larynx.


Condition Intervention Phase
Head and Neck Cancer
Drug: cisplatin
Drug: fluorouracil
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: PHASE II STUDY ON LARYNX PRESERVATION COMPARING INDUCTION CHEMOTHERAPY AND RADIOTHERAPY VERSUS ALTERNATING CHEMO-RADIOTHERAPY IN RESECTABLE HYPOPHARYNX AND LARYNX CANCERS

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Estimated Enrollment: 564
Study Start Date: July 1996
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare relapse-free survival and larynx preservation in patients with resectable hypopharyngeal or laryngeal cancer treated with sequential vs alternating cisplatin and fluorouracil and radiotherapy.
  • Compare the health-related quality of life in patients treated with these regimens.
  • Compare the cost-effectiveness of these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by performance status, disease site, tumor stage, node stage, and center.

Patients are randomized to one of two treatment arms. Both groups may receive either conventional radiotherapy in single daily fractions, 5 days per week, for 7 weeks (option 1) or hyperfractionated radiotherapy in 2 daily fractions, 5 days per week, for 4-5 weeks (option 2), according to institutional policy.

  • Arm I: Patients receive cisplatin and fluorouracil every 3 weeks. Patients with a complete or partial response on day 42 receive 2 additional courses of chemotherapy followed by 7 weeks of radiotherapy beginning on day 80. After radiotherapy, patients with a complete remission enter follow-up; those with a partial remission proceed to surgery. Patients with stable or progressive disease proceed immediately to surgery with or without postoperative radiotherapy.
  • Arm II: Patients receive cisplatin and fluorouracil every 3 weeks for 4 courses. Patients treated on radiotherapy option 1 are evaluated 2 months after completion of radiotherapy; those with a complete remission enter follow-up while all others proceed to surgery. Patients treated on option 2 are evaluated on day 42; those with a partial or complete response complete chemoradiotherapy and are then evaluated and treated like option 1 patients. Patients with stable or progressive disease on day 42 proceed to surgery with or without a third course of chemotherapy on week 7.

Patients are followed every 3 months for 3 years and at least every 6 months thereafter.

PROJECTED ACCRUAL: A total of 564 patients will be accrued for this study within 4 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically proven squamous cell carcinoma of the head and neck, including:

    • Stage III/IV cancer of the glottic or supraglottic larynx

      • Eligible T4 tumor defined as:

        • Bulging the valleculae
        • Bulging the hyothyroid membrane
        • Minimal thyroid cartilage invasion or suspicion of invasion on imaging
    • Stage II/III/IV cancer of the pyriform sinus or of the hypopharyngeal aspect of the aryepiglottic fold (with or without extension to postcricoid area)

      • No massive destruction of the thyroid cartilage
      • No continuity between primary tumor and a lymph node
  • Operable on first attempt (as assessed by head and neck surgeon) by classical total laryngectomy with or without partial pharyngectomy

    • No requirement for extended surgery (circumferential pharyngolaryngectomy)
    • No tumor suitable for partial (functional) surgery or requiring extended surgery that necessitates any kind of flap for closure
    • No N2c tumor unless no requirement for bilateral resection of internal jugular veins
  • Measurable or evaluable disease by panendoscopy and CT scan or MRI

    • Esophagoscopy required
    • Bronchofiberscopy recommended
  • No requirement for tracheotomy

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2 OR
  • WHO 0-2

Hematopoietic:

  • WBC at least 4,000/mm^3

Hepatic:

  • Bilirubin no greater than 2.0 times normal

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance at least 60 mL/min

Other:

  • No medical, psychological, or geographical condition that precludes study compliance
  • No serious nonmalignant systemic disease
  • No second malignancy except:

    • Carcinoma in situ of the cervix
    • Adequately treated nonmelanomatous skin cancer
  • No poor nutritional status unlikely to be restored to fair status within 3 weeks
  • No contraindication to CT scan or general anesthesia

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior anticancer biologic therapy

Chemotherapy

  • No prior anticancer chemotherapy

Endocrine therapy

  • No prior anticancer endocrine therapy

Radiotherapy

  • No prior anticancer radiotherapy

Surgery

  • See Disease Characteristics

Other

  • No other prior anticancer therapy
  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: NCT00002839

Locations
Belgium
Algemeen Ziekenhuis Middelheim
Antwerp, Belgium, 2020
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
France
CHR de Besancon - Hopital Jean Minjoz
Besancon, France, 25030
Centre Regional Francois Baclesse
Caen, France, 14076
Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
Dijon, France, 21079
Centre Hospitalier Universitaire de Dijon
Dijon, France, 21033
Centre Hospitalier Regional et Universitaire de Lille
Lille, France, 59037
Centre Oscar Lambret
Lille, France, 59020
CRLCC Nantes - Atlantique
Nantes-Saint Herblain, France, 44805
Centre Antoine Lacassagne
Nice, France, 06189
Hopital Charles Nicolle
Rouen, France, 76031
Centre Alexis Vautrin
Vandoeuvre-les-Nancy, France, 54511
Israel
Rambam Medical Center
Haifa, Israel, 31096
Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori
Milano (Milan), Italy, 20133
Ospedale Civile Monselice
Monselice, Padova, Italy, 35043
Azienda Ospedaliera "Santa Maria Degli Angeli"
Pordenone, Italy, 33170
Netherlands
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands, 1007 MB
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6202 AZ
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Jean-Louis Lefebvre, MD Centre Oscar Lambret
Study Chair: Jean-Claude Horiot, MD, PhD Centre de Lutte Contre le Cancer Georges-Francois Leclerc
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00002839     History of Changes
Other Study ID Numbers: EORTC-24954
Study First Received: November 1, 1999
Last Updated: January 7, 2013
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage II squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx

Additional relevant MeSH terms:
Head and Neck Neoplasms
Laryngeal Diseases
Neoplasms by Site
Neoplasms
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
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

ClinicalTrials.gov processed this record on August 21, 2014