Fractionated Radiation Therapy in Treating Advanced Squamous Cell Carcinoma of the Head and Neck

Head and Neck Cancer Clinical Trial

Official title:

Phase III Randomized Comparison of Radiotherapy Fractionation in Advanced Squamous Cell Carcinoma of the Head and Neck: Twice-Daily Hyperfractionation vs Split-Course Accelerated Hyperfractionation vs Accelerated Fractionation With Concomitant Boost vs Standard Fractionation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00771641
• Other study ID #: RTOG-9003
• Secondary ID: CDR0000076475
• Status: Completed
• Phase: Phase 3
• First received: October 10, 2008
• Last updated: January 23, 2014
• Est. completion date: November 2013

Study information

• Verified date: January 2014
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Patient abstract not available

PURPOSE: Patient abstract not available

Description:

OBJECTIVES: I. Determine whether hyperfractionation and/or accelerated fractionation (split-course or with a concomitant boost) improves the locoregional control rate over standard fractionation radiotherapy in patients with advanced squamous cell carcinomas of the head and neck. II. Determine the disease-free survival and overall survival of these patients treated with different radiotherapy fractionation schemes. III. Determine the acute and late toxicities of each fractionation schedule. IV. Compare the quality of life on the two regimens.

OUTLINE: Randomized study. Arm I: Radiotherapy. Irradiation of primary tumor and involved and at-risk nodal areas using linear accelerators with photon energies of 1.25-6.0 MV (dual energy arrangements may also use a beam greater than 6.0 MV), electrons of 4-25 MV, or Co60. Standard fractionation. Arm II: Radiotherapy. Targets and equipment as in Arm I. Hyperfractionation. Arm III: Radiotherapy. Targets and equipment as in Arm I. Accelerated split-course hyperfractionation. Arm IV: Radiotherapy. Targets and equipment as in Arm I. Accelerated fractionation with concomitant boost.

PROJECTED ACCRUAL: A total of 1,080 patients (270/arm) will be accrued over 5.75 years. If excessive toxicity is noted in any arm after entry of 324 and 634 patients, that arm may be closed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1113
• Est. completion date: November 2013
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS: Histologically proven squamous cell carcinoma of the head and neck, including lymphoepithelioma and anaplastic carcinoma Biopsy from the primary or regional nodes acceptable No adenocarcinomas The following stages and sites are eligible: Stage III/IV oral cavity, including: Anterior 2/3 of the tongue Buccal mucosa Floor of mouth Hard palate Gingiva Retromolar trigone Stage III/IV oropharynx, including: Tonsil and pillars Faucial arch and soft palate Posterolateral pharyngeal walls Stage II/III/IV base of the tongue and hypopharynx Stage III/IV supraglottic larynx, including: Ventricular band Arytenoid Supra- and infrahyoid epiglottis Aryepiglottic fold (tumors at glottic and subglottic sites excluded) Nonpalpable nodes detected only on CT or MRI must be at least 1.0 cm in diameter or contain necrosis to prove N+ disease No metastasis below the clavicle clinically or radiologically

PATIENT CHARACTERISTICS: Age: At least 18 Performance status: Karnofsky 60-100% Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Medically able to withstand radiotherapy No second malignancy within 5 years except nonmelanomatous skin cancer Follow-up by participating radiotherapist required

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to head and neck No planned combined external beam and interstitial boost irradiation Surgery: No prior surgery (other than biopsy) No planned combined pre- or postoperative programs Radical neck dissections allowed if lymph nodes are greater than 3 cm prior to radiotherapy or involvement persists after treatment Resection of persistent disease at the primary site may be performed 6 weeks after completion of radiotherapy

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Procedure:
• conventional surgery

Radiation:
• low-LET cobalt-60 gamma ray therapy

• low-LET electron therapy

• low-LET photon therapy

• radiation therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

References & Publications (35)

Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, Fu KK, Milas L. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002 Dec 15;62(24):7350-6. — View Citation

Calvin DP, Hammond ME, Pajak TF, et al.: Microvessel density (MVD)> 60 does not predict for outcome in advanced head and neck squamous cell carcinoma (HNSCC): results of a prospective study from the RTOG 90-03 trial. [Abstract] Int J Radiat Oncol Biol Phy

Calvin DP, Hammond ME, Pajak TF, Trotti AM, Meredith RF, Rotman M, Jones CU, Byhardt RW, Demas WF, Ang KK, Fu KK; Radiation Therapy Oncology Group 90-03 Trial. Microvessel density >or=60 does not predict for outcome after radiation treatment for locally a — View Citation

Chung CH, Dignam J, Hammond ME, et al.: Association of high Gli1 expression with poor survival in head and neck cancer patients treated with radiation therapy (RTOG 9003). [Abstract] J Clin Oncol 28 (Suppl 15): A-5552, 2010.

Chung CH, Dignam JJ, Hammond ME, Klimowicz AC, Petrillo SK, Magliocco A, Jordan R, Trotti A, Spencer S, Cooper JS, Le QT, Ang KK. Glioma-associated oncogene family zinc finger 1 expression and metastasis in patients with head and neck squamous cell carcin — View Citation

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. — View Citation

Cullen KJ, Nikitakis N, Goloubeva O, et al.: Effect of elevated expression of GST-p and p53 on prognosis in head and neck cancer patients treated with chemoradiotherapy but not radiotherapy alone: An analysis of RTOG trials 9003 and 9501. [Abstract] J Clin Oncol 26 (Suppl 15): A-6013, 2008.

Dilling TJ, Bae K, Paulus R, Watkins-Bruner D, Garden AS, Forastiere A, Kian Ang K, Movsas B. Impact of gender, partner status, and race on locoregional failure and overall survival in head and neck cancer patients in three radiation therapy oncology group trials. Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):e101-9. doi: 10.1016/j.ijrobp.2011.01.013. Epub 2011 May 5. — View Citation

Eldridge B, Rabinovitch R, Berkey BA, et al.: The impact of baseline nutritional support on treatment outcome in patients with locally advanced squamous cell cancer of the head and neck treated with definitive radiotherapy: report of the Radiation Therapy

Fisher J, Scott C, Fu K, et al.: Randomized study comparing quality of life between standard fractionation radiotherapy and altered fractionation schemas in patients with locally advanced squamous cell cancer of the head and neck. [Abstract] Proceedings o

Fisher J, Scott C, Fu K, et al.: Treatment, patient and tumor characteristics impact quality of life (QOL) in patients with locally advanced head and neck cancer: report of the Radiation Therapy Oncology Group (RTOG) trial 90-03. [Abstract] Int J Radiat O

Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to stand — View Citation

Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH, Ang KK. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012 Jun 10;30(17):2102-11. doi: 10.1200/JCO.2011.38.4099. Epub 2012 May 7. — View Citation

Hammond E, Berkey BA, Fu KK, Trotti A, Meredith RF, Jones CU, Byhardt R, Horwitz EM, Ang KK. P105 as a prognostic indicator in patients irradiated for locally advanced head-and-neck cancer: a clinical/laboratory correlative analysis of RTOG-9003. Int J Ra — View Citation

Hammond E, Pajak T, Fu K, et al.: p105 as a prognostic indicator in patients irradiated for locally advanced head and neck cancer: a clinical/laboratory correlative analysis of RTOG 9003. [Abstract] Proceedings of the International Conference on Head and

Konski A, Berkey B, Ang KK, et al.: The effect of education level on outcome of patients treated on Radiation Therapy Oncology Group (RTOG) protocol 90-03. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-992, 2002.

Konski A, Berkey BA, Kian Ang K, Fu KK. Effect of education level on outcome of patients treated on Radiation Therapy Oncology Group Protocol 90-03. Cancer. 2003 Oct 1;98(7):1497-503. — View Citation

Konski A, Scott C, Ang KK, et al.: Cost-utility analysis of RTOG 90-03: phase III randomized study comparing altered fractionation to standard fractionation radiotherapy for locally advanced head and neck squamous cell carcinoma. [Abstract] Int J Radiat O

Konski AA, Bhargavan M, Owen J, et al.: Altered fractionated radiotherapy is cost-effective in the treatment of locally advanced head and neck cancer: an economic analysis of Radiation Therapy Oncology Group (RTOG) 90-03. [Abstract] J Clin Oncol 24 (Suppl

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.

Konski AA, Scott CB, Ang KK, et al.: Does dose escalation of radiotherapy (RT) improve quality-adjusted survival (QAS) in unresectable head and neck cancer (HNC) patients (Pts)? Radiation Therapy Oncology Group (RTOG) study 90-03. [Abstract] Proceedings o

Konski AA, Winter K, Cole BF, Ang KK, Fu KK. Quality-adjusted survival analysis of Radiation Therapy Oncology Group (RTOG) 90-03: phase III randomized study comparing altered fractionation to standard fractionation radiotherapy for locally advanced head a — View Citation

Kumar P, Harris J, Garden AS, et al.: Outcome comparisons of four Radiation Therapy Oncology Group (RTOG) trials in patients with stage IV-T4 head and neck (H/N) cancer: encouraging results using intra-arterial (IA) cisplatin (P) and concurrent radiation therapy (RT). [Abstract] J Clin Oncol 22 (Suppl 14): A-5527, 494s, 2004.

Le QT, Harris J, Magliocco AM, Kong CS, Diaz R, Shin B, Cao H, Trotti A, Erler JT, Chung CH, Dicker A, Pajak TF, Giaccia AJ, Ang KK. Validation of lysyl oxidase as a prognostic marker for metastasis and survival in head and neck squamous cell carcinoma: R — View Citation

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.

Owen J, Grigsby P, Caldwell T, et al.: Can costs be measured and predicted by modelling within a cooperative clinical trials group? Economic methodological pilot studies of Radiation Therapy Oncology Group studies 9003 and 9104. [Abstract] Int J Radiat Oncol Biol Phys 45 (3 suppl): A-150, 225, 1999.

Owen JB, Grigsby PW, Caldwell TM, Konski AA, Johnson DJ, Demas WF, Movsas B, Jones CU, Wasserman TH. Can costs be measured and predicted by modeling within a cooperative clinical trials group? Economic methodologic pilot studies of the radiation therapy oncology group (RTOG) studies 90-03 and 91-04. Int J Radiat Oncol Biol Phys. 2001 Mar 1;49(3):633-9. — View Citation

Pajak TF, Trotti A, Gwede CK, et al.: The TAME risk classification system: acute toxicity burden and IPD analysis of RTOG 90-03. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-217, S131, 2005.

Rabinovitch R, Grant B, Berkey BA, Raben D, Ang KK, Fu KK, Cooper JS; Radiation Therapy Oncology Group. Impact of nutrition support on treatment outcome in patients with locally advanced head and neck squamous cell cancer treated with definitive radiother — View Citation

Sanabria A, Carvalho AL, Kowalski LP. Is nutrition support related to a poor prognosis in head and neck cancer patients? Thoughts about the secondary analysis of RTOG trial 90-03. Head Neck. 2007 May;29(5):518-9; author reply 519-20. — View Citation

Schumaker L, Nikitakis N, Goloubeva O, Tan M, Taylor R, Cullen KJ. Elevated expression of glutathione S-transferase pi and p53 confers poor prognosis in head and neck cancer patients treated with chemoradiotherapy but not radiotherapy alone. Clin Cancer Res. 2008 Sep 15;14(18):5877-83. doi: 10.1158/1078-0432.CCR-08-0998. — View Citation

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. Epub 2007 Sep 24. — View Citation

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. — View Citation

Trotti A, Fu KK, Pajak TF, et al.: Long term outcomes of RTOG 90-03: a comparison of hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinoma. [Abstract] Int J Radiat

Tu X, Berkey BA, Zhang HZ, et al.: Impact of EGFR expression on the response of advanced head and neck carcinomas to concomitant boost radiotherapy in a RTOG phase III trial (90-03). Int J Radiat Oncol Biol Phys 57 (2 Suppl): S157, 2003.

* Note: There are 35 references in all — Click here to view all references