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

NCT ID: NCT00002839

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 564 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-07-31

Brief Summary

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.

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

cisplatin

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Louis Lefebvre, MD

Role: STUDY_CHAIR

Centre Oscar Lambret

Jean-Claude Horiot, MD, PhD

Role: STUDY_CHAIR

Centre Georges Francois Leclerc

Locations

Algemeen Ziekenhuis Middelheim

Antwerp, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

CHR de Besancon - Hopital Jean Minjoz

Besançon, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Hospitalier Universitaire de Dijon

Dijon, , France

Centre de Lutte Contre le Cancer, Georges-Francois Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Centre Hospitalier Regional et Universitaire de Lille

Lille, , France

CRLCC Nantes - Atlantique

Nantes-Saint Herblain, , France

Centre Antoine Lacassagne

Nice, , France

Hopital Charles Nicolle

Rouen, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Rambam Medical Center

Haifa, , Israel

Istituto Nazionale per lo Studio e la Cura dei Tumori

Milano (Milan), , Italy

Ospedale Civile Monselice

Monselice, Padova, , Italy

Azienda Ospedaliera "Santa Maria Degli Angeli"

Pordenone, , Italy

Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Countries

Belgium; France; Israel; Italy; Netherlands; Switzerland

References

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. doi: 10.1093/jnci/djn460. Epub 2009 Jan 27.

Reference Type: RESULT

PMID: 19176454 (View on PubMed)

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.

Reference Type: RESULT

Bottomley A, Tridello G, Coens C, Rolland F, Tesselaar ME, Leemans CR, Hupperets P, Licitra L, Vermorken JB, Van Den Weyngaert D, Truc G, Barillot I, Lefebvre JL. An international phase 3 trial in head and neck cancer: quality of life and symptom results: EORTC 24954 on behalf of the EORTC Head and Neck and the EORTC Radiation Oncology Group. Cancer. 2014 Feb 1;120(3):390-8. doi: 10.1002/cncr.28392. Epub 2013 Oct 25.

Reference Type: DERIVED

PMID: 24452673 (View on PubMed)

Other Identifiers

EORTC-24954

Identifier Type: -

Identifier Source: org_study_id