Radiation Therapy With or Without Chemotherapy in Treating Patients With Advanced Cancer of the Larynx

NCT ID: NCT00002496

Last Updated: 2014-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 1992-08-31
• Study Completion Date: 2013-11-30

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. It is not yet known if chemotherapy plus radiation therapy is more effective than radiation therapy alone in treating patients with advanced cancer of the larynx.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without chemotherapy in treating patients with advanced cancer of the larynx.

Detailed Description

OBJECTIVES: I. Compare, in a phase III setting, overall and disease-free survival with preservation of laryngeal function in patients with stage III/IV squamous cell carcinoma of the glottic and supraglottic larynx treated with cisplatin/fluorouracil (CDDP/5-FU) followed by radiotherapy vs. concomitant radiotherapy plus CDDP vs. radiotherapy alone. II. Compare the tumor response after completion of chemotherapy but prior to initiation of radiotherapy with that following completion of radiotherapy and concurrent chemotherapy. III. Compare the patterns of relapse (local and regional recurrence and distant metastasis) with these treatments. IV. Compare the incidence of second primary tumors in patients treated on these three regimens. V. Compare the acute and chronic adverse effects of these three regimens. VI. Compare the morbidity experienced with neck dissection and/or laryngeal salvage surgery following treatment with these regimens. VII. Compare quality of life of patients with laryngeal preservation vs. patients requiring salvage laryngectomies. VIII. Compare the quality of life of patients receiving radiotherapy alone vs. those receiving chemotherapy as well.

OUTLINE: Randomized study. Patients on any arm, clinically staged N+ undergo neck dissection following completion of radiotherapy. Arm I: 2-Drug Combination Chemotherapy followed by Radiotherapy. Cisplatin, CDDP, NSC-119875; Fluorouracil, 5-FU, NSC-19893; followed by regional irradiation using linear accelerators with photon energies of 1.25-6 MV, electron energies of 8-17 MeV, or Co60. Arm II: Radiotherapy plus Single-Agent Chemotherapy/Radiosensitization. Regional irradiation using equipment as in Arm I; plus CDDP. Arm III: Radiotherapy. Regional irradiation using equipment as in Arm I.

PROJECTED ACCRUAL: 546 patients (182/arm) will be entered over approximately 3 years. If any arm is clearly inferior in laryngectomy-free survival after 137 patients have completed 2 years of follow-up study, that arm will be closed to further accrual. A second interim analysis will be conducted after 410 patients have completed 2 years of follow-up.

Conditions

Head and Neck Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

chemotherapy

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

low-LET cobalt-60 gamma ray therapy

Intervention Type: RADIATION

low-LET electron therapy

Intervention Type: RADIATION

low-LET photon therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior therapy Chemotherapy: No prior therapy Endocrine therapy: No prior therapy Radiotherapy: No prior radiotherapy to the head and neck Surgery: No prior therapy

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helmuth Goepfert, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

George L. Adams, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

David E. Schuller, MD

Role: STUDY_CHAIR

Ohio State University Comprehensive Cancer Center

Locations

CCOP - Colorado Cancer Research Program, Inc.

Denver, Colorado, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Veterans Affairs Medical Center - Atlanta (Decatur)

Decatur, Georgia, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Indiana University Cancer Center

Indianapolis, Indiana, United States

Veterans Affairs Medical Center - Indianapolis (Roudebush)

Indianapolis, Indiana, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

New England Medical Center Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Veterans Affairs Medical Center - East Orange

East Orange, New Jersey, United States

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Ireland Cancer Center

Cleveland, Ohio, United States

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Pretoria Academic Hospital

Pretoria, , South Africa

Countries

United States; South Africa

References

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Reference Type: BACKGROUND

PMID: 21549515 (View on PubMed)

Coyne JC, Pajak TF, Harris J, Konski A, Movsas B, Ang K, Watkins Bruner D; Radiation Therapy Oncology Group. Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer. 2007 Dec 1;110(11):2568-75. doi: 10.1002/cncr.23080.

Reference Type: BACKGROUND

PMID: 17955501 (View on PubMed)

Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, Forastiere A, Ang KK. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008 Jul 20;26(21):3582-9. doi: 10.1200/JCO.2007.14.8841. Epub 2008 Jun 16.

Reference Type: BACKGROUND

PMID: 18559875 (View on PubMed)

Siddiqui F, Pajak TF, Watkins-Bruner D, Konski AA, Coyne JC, Gwede CK, Garden AS, Spencer SA, Jones C, Movsas B. Pretreatment quality of life predicts for locoregional control in head and neck cancer patients: a radiation therapy oncology group analysis. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):353-60. doi: 10.1016/j.ijrobp.2007.06.024. Epub 2007 Sep 24.

Reference Type: BACKGROUND

PMID: 17889449 (View on PubMed)

Spiegel D, Kraemer HC. Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer. 2008 May 15;112(10):2326-7; author reply 2327-8. doi: 10.1002/cncr.23435. No abstract available.

Reference Type: BACKGROUND

PMID: 18338746 (View on PubMed)

Konski A, Bhargavan M, Owen J, et al.: The price of failure: economic analysis of recurrence and complications of patients treated on RTOG 91-11. [Abstract] The American Radium Society 89th Annual Meeting, May 5-29, 2007, Amsterdam, Netherlands. A-SS-6, 3, 2007.

Reference Type: BACKGROUND

O'Meara EA, Machtay M, Moughan J, et al.: Associations between radiation doses to pharyngeal regions and severe late toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy: an RTOG analysis. [Abstract] Int J Radiat Oncol Biol Phys 69 (3): A-96, S54-5, 2007.

Reference Type: BACKGROUND

Konski AA, Bhargavan M, Owen J, et al.: The addition of chemotherapy to radiation is cost-effective in the treatment of patients with locally advanced laryngeal cancer: an economic analysis of Radiation Therapy Oncology Group (RTOG) 91-11. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-115, S66, 2006.

Reference Type: BACKGROUND

Machtay M, Moughan J, Trotti A, et al.: Pre-treatment and treatment related risk factors for severe late toxicity after chemo-RT for head and neck cancer: an RTOG analysis. [Abstract] J Clin Oncol 24 (Suppl 18): A-5500, 280s, 2006.

Reference Type: BACKGROUND

Mukherji SK, Toledano AY, Beldon C, Schmalfuss IM, Cooper JS, Sicks JD, Amdur R, Sailer S, Loevner LA, Kousouboris P, Ang K. Interobserver reliability of computed tomography-derived primary tumor volume measurement in patients with supraglottic carcinoma. Cancer. 2005 Jun 15;103(12):2616-22. doi: 10.1002/cncr.21072.

Reference Type: BACKGROUND

PMID: 15887218 (View on PubMed)

Bourhis J, Amand C, Pignon JP, et al.: Update of MACH-NC (Meta-Analysis of Chemotherapy In Head & Neck Cancer ) database focused on concomitant chemotherapy. [Abstract] J Clin Oncol 12 (Suppl 14): A-5505, 489s, 2004.

Reference Type: BACKGROUND

Konski AA, Pajak T, Movsas B, et al.: Socio-demographic variables influence outcome in Radiation Therapy Oncology Group head and neck trials. [Abstract] Proceedings of the American Society of Clinical Oncology 22 (Suppl 14): A-6043, 529s, 2004.

Reference Type: BACKGROUND

Movsas B, Konski A, Pajak T, et al.: Quality of life (QOL) variables influence local regional control in Radiation Therapy Oncology Group (RTOG) headsneck trials (9003 and 9111). [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-199, S252, 2004.

Reference Type: BACKGROUND

Forastiere AA, Maor M, Weber RS, et al.: Long-term results of intergroup RTOG 91-11: a phase III trial to preserve the larynx--Induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy. [Abstract] J Clin Oncol 24 (Suppl 18): A-5517, 284s, 2006.

Reference Type: RESULT

Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. doi: 10.1056/NEJMoa031317.

Reference Type: RESULT

PMID: 14645636 (View on PubMed)

Weber RS, Berkey BA, Forastiere A, Cooper J, Maor M, Goepfert H, Morrison W, Glisson B, Trotti A, Ridge JA, Chao KS, Peters G, Lee DJ, Leaf A, Ensley J. Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91-11. Arch Otolaryngol Head Neck Surg. 2003 Jan;129(1):44-9. doi: 10.1001/archotol.129.1.44.

Reference Type: RESULT

PMID: 12525193 (View on PubMed)

Maor MH, Berkey B, Forastiere A, et al.: Larynx preservation and tumor control in stage III and IV laryngeal cancer: a three-arm randomized intergroup trial: RTOG 91-11. [Abstract] Int J Radiat Oncol Biol Phys 54(2 suppl 1): 2-3, 2002.

Reference Type: RESULT

Wolf GT. Commentary: phase III trial to preserve the larynx: induction chemotherapy and radiotherapy versus concurrent chemotherapy and radiotherapy versus radiotherapy--intergroup trial R91-11. J Clin Oncol. 2001 Sep 15;19(18 Suppl):28S-31S. No abstract available.

Reference Type: RESULT

PMID: 11560968 (View on PubMed)

Other Identifiers

CDR0000077756

Identifier Type: -

Identifier Source: secondary_id

EST-R9111

Identifier Type: -

Identifier Source: secondary_id

SWOG-9201

Identifier Type: -

Identifier Source: secondary_id

RTOG-9111

Identifier Type: -

Identifier Source: org_study_id