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

Sponsor:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002839

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Fluorouracil Cisplatin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	564
Study Start Date:	July 1996

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

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
Centre Alexis Vautrin
Vandoeuvre-les-Nancy, France, 54511
Centre Antoine Lacassagne
Nice, France, 06189
Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
Dijon, France, 21079
CHR de Besancon - Hopital Jean Minjoz
Besancon, France, 25030
Centre Hospitalier Universitaire de Dijon
Dijon, France, 21033
Centre Oscar Lambret
Lille, France, 59020
Centre Regional Francois Baclesse
Caen, France, 14076
Centre Hospitalier Regional et Universitaire de Lille
Lille, France, 59037
CRLCC Nantes - Atlantique
Nantes-Saint Herblain, France, 44805
Hopital Charles Nicolle
Rouen, France, 76031
Israel
Rambam Medical Center
Haifa, Israel, 31096
Italy
Azienda Ospedaliera "Santa Maria Degli Angeli"
Pordenone, Italy, 33170
Istituto Nazionale per lo Studio e la Cura dei Tumori
Milano (Milan), Italy, 20133
Ospedale Civile Monselice
Monselice, Padova, Italy, 35043
Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6202 AZ
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands, 1007 MB
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Investigator:	Jean-Louis Lefebvre, MD	Centre Oscar Lambret
Investigator:	Jean-Claude Horiot, MD, PhD	Centre de Lutte Contre le Cancer Georges-Francois Leclerc

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; EORTC Head and Neck Cancer Cooperative Group; EORTC Radiation Oncology Group. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009 Feb 4;101(3):142-52. Epub 2009 Jan 27.

Lefebvre J, Horiot J, Rolland F, et al.: Phase III study on larynx preservation comparing induction chemotherapy and radiotherapy versus alternating chemoradiotherapy in resectable hypopharynx and larynx cancers. EORTC protocol 24954-22950. [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA6016, 303s, 2007.

Study ID Numbers:	CDR0000065056, EORTC-24954
Study First Received:	November 1, 1999
Last Updated:	March 26, 2009
ClinicalTrials.gov Identifier:	NCT00002839 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Cisplatin
Radiation-Sensitizing Agents
Head and Neck Neoplasms
Fluorouracil
Therapeutic Uses

ClinicalTrials.gov processed this record on November 09, 2009