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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
cisplatin
fluorouracil
conventional surgery
neoadjuvant therapy
radiation therapy
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Algemeen Ziekenhuis Middelheim
  • Universitair Ziekenhuis Antwerpen
  • CHR de Besancon - Hopital Jean Minjoz
  • Centre Regional Francois Baclesse
  • Centre Hospitalier Universitaire de Dijon
  • Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
  • Centre Oscar Lambret
  • Centre Hospitalier Regional et Universitaire de Lille
  • CRLCC Nantes - Atlantique
  • Centre Antoine Lacassagne
  • Hopital Charles Nicolle
  • Centre Alexis Vautrin
  • Rambam Medical Center
  • Istituto Nazionale per lo Studio e la Cura dei Tumori
  • Ospedale Civile Monselice
  • Azienda Ospedaliera "Santa Maria Degli Angeli"
  • Vrije Universiteit Medisch Centrum
  • Leiden University Medical Center
  • Academisch Ziekenhuis Maastricht
  • Centre Hospitalier Universitaire Vaudois

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
July 6, 2018
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00002839
Brief Title
Combination Chemotherapy Plus Radiation Therapy To Preserve the Larynx in Patients With Cancer of the Hypopharynx or Larynx
Official Title
PHASE II STUDY ON LARYNX PRESERVATION COMPARING INDUCTION CHEMOTHERAPY AND RADIOTHERAPY VERSUS ALTERNATING CHEMO-RADIOTHERAPY IN RESECTABLE HYPOPHARYNX AND LARYNX CANCERS
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
July 1996 (undefined)
Primary Completion Date
May 2004 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
564 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Type
Procedure
Intervention Name(s)
neoadjuvant therapy
Intervention Type
Radiation
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Louis Lefebvre, MD
Organizational Affiliation
Centre Oscar Lambret
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jean-Claude Horiot, MD, PhD
Organizational Affiliation
Centre Georges Francois Leclerc
Official's Role
Study Chair
Facility Information:
Facility Name
Algemeen Ziekenhuis Middelheim
City
Antwerp
ZIP/Postal Code
2020
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
CHR de Besancon - Hopital Jean Minjoz
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
Centre Regional Francois Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Centre Hospitalier Universitaire de Dijon
City
Dijon
ZIP/Postal Code
21033
Country
France
Facility Name
Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Centre Hospitalier Regional et Universitaire de Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CRLCC Nantes - Atlantique
City
Nantes-Saint Herblain
ZIP/Postal Code
44805
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Hopital Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Centre Alexis Vautrin
City
Vandoeuvre-les-Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Istituto Nazionale per lo Studio e la Cura dei Tumori
City
Milano (Milan)
ZIP/Postal Code
20133
Country
Italy
Facility Name
Ospedale Civile Monselice
City
Monselice, Padova
ZIP/Postal Code
35043
Country
Italy
Facility Name
Azienda Ospedaliera "Santa Maria Degli Angeli"
City
Pordenone
ZIP/Postal Code
33170
Country
Italy
Facility Name
Vrije Universiteit Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1007 MB
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 CA
Country
Netherlands
Facility Name
Academisch Ziekenhuis Maastricht
City
Maastricht
ZIP/Postal Code
6202 AZ
Country
Netherlands
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
19176454
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
PubMed Identifier
24452673
Citation
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.
Results Reference
derived

Learn more about this trial

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

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