Radiation Therapy With or Without Chemotherapy in Treating Patients With Head and Neck Cancer That Has Been Removed During Surgery

• ClinicalTrials.gov Identifier: NCT00002670
• Recruitment Status: Completed
• First Posted: June 10, 2004
• Last Update Posted: January 24, 2014
• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Southwest Oncology Group
• Information provided by (Responsible Party): Radiation Therapy Oncology Group

Tracking Information

• First Submitted Date: November 1, 1999
• First Posted Date: June 10, 2004
• Last Update Posted Date: January 24, 2014
• Study Start Date: September 1995
• Actual Primary Completion Date: July 2002 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Radiation Therapy With or Without Chemotherapy in Treating Patients With Head and Neck Cancer That Has Been Removed During Surgery
• Official Title: Phase III Intergroup Trial of Surgery Followed by (1) Radiotherapy vs. (2) Radiochemotherapy For Resectable High Risk Squamous Cell Carcinoma of the Head and Neck

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy plus cisplatin is more effective than radiation therapy alone in treating patients with head and neck cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus cisplatin with radiation therapy alone in treating patients with head and neck cancer that has been removed during surgery.

Detailed Description

OBJECTIVES: I. Evaluate locoregional control rates, patterns of first failure, and overall and disease-free survival in patients with advanced squamous cell carcinoma of the head and neck at high risk of locoregional recurrence who are treated postoperatively with concurrent cisplatin and radiotherapy. II. Compare the toxicity of concurrent chemoradiotherapy vs. radiotherapy alone in the postoperative setting.

OUTLINE: Randomized study. Arm I: Radiotherapy. Involved-field irradiation using Co60, 1-6 MV photons, or electrons. Arm II: Radiotherapy plus Single-Agent Chemotherapy. Irradiation as in Arm I; plus Cisplatin, CDDP, NSC-119875.

PROJECTED ACCRUAL: 438 patients will be entered over approximately 5 years.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Cancer

Intervention

• Drug: chemotherapy
• Drug: cisplatin
• Radiation: low-LET cobalt-60 gamma ray therapy
• Radiation: low-LET electron therapy
• Radiation: low-LET photon therapy

Study Arms

• Active Comparator: Radiation therapy
  Radiation therapy - 60 Gy in 6 weeks (2 Gy once a day, 5 x a week)
  Interventions:

  • Radiation: low-LET cobalt-60 gamma ray therapy
  • Radiation: low-LET electron therapy
  • Radiation: low-LET photon therapy
• Experimental: Radiation therapy plus cisplatin
  Radiation therapy - 60 Gy in 6 weeks (2 Gy once a day, 5 x a week) plus Cisplatin-100 mg/m2 i.v. on days 1,22 and 43 with radiation therapy.
  Interventions:

  • Drug: chemotherapy
  • Drug: cisplatin
  • Radiation: low-LET cobalt-60 gamma ray therapy
  • Radiation: low-LET electron therapy
  • Radiation: low-LET photon therapy

Publications *

• Cullen KJ, Nikitakis N, Goloubeva O, et al.: Effect of elevated expression of GST-π 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.
• 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.
• Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005 Oct;27(10):843-50.
• Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1198-205. doi: 10.1016/j.ijrobp.2012.05.008. Epub 2012 Jun 30.
• Cooper JS, Pajak TF, Forastiere AA, et al.: Long-term survival results of a phase III intergroup trial (RTOG 95-01) of surgery followed by radiotherapy vs. radiochemotherapy for resectable high risk squamous cell carcinoma of the head and neck. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-25, S14-5, 2006.
• Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44.
• Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiochemotherapy in high-risk SCCA of the head and neck: initial report of RTOG 9501/intergroup phase III trial. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-903, 2002.
• Cooper JS, Pajak TF, Forastiere AA, et al.: Patterns of failure for resected advanced head & neck cancer treated by concurrent chemotherapy and radiation therapy: an analysis of RTOG 9501/intergroup phase III trial. [Abstract] Int J Radiat Oncol Biol Phys 54(2 suppl 1): 2, 2002.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 6, 2013): 459
• Original Enrollment: Not Provided
• Actual Study Completion Date: November 2013
• Actual Primary Completion Date: July 2002 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS: Biopsy-proven squamous cell carcinoma of one of the following sites: Hypopharynx Larynx Oral cavity Oropharynx At least 1 of the following high-risk factors required: Histologic extracapsular nodal extension Histologic involvement of 2 or more regional lymph nodes Microscopically positive mucosal margins Complete resection of all visible and palpable disease Therapy must begin within 8 weeks of tumor-related surgery Bilateral resections may or may not be performed simultaneously Eligibility window begins with first definitive surgery Neck dissection not required for T4 N0, truly midline supraglottic tumors No tumors of the lip, nasopharynx, or sinuses No synchronous or concurrent head and neck tumors No evidence of distant metastasis Concurrent registration on Fixed Tumor Repository Study allowed

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60%-100% Hematopoietic: WBC at least 3,500 Platelets at least 100,000 Hepatic: Not specified Renal: Creatinine clearance greater than 50 mL/min Other: No medical contraindication to protocol therapy No second malignancy within 5 years No pregnant or nursing women

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to head and neck region Surgery: See Disease Characteristics

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: South Africa, United States

Administrative Information

• NCT Number: NCT00002670
• Other Study ID Numbers: RTOG-9501; CDR0000064279; E-R9501; SWOG-9515
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Radiation Therapy Oncology Group
• Study Sponsor: Radiation Therapy Oncology Group

Collaborators

• National Cancer Institute (NCI)
• Eastern Cooperative Oncology Group
• Southwest Oncology Group

Investigators

• Study Chair: Jay S. Cooper, MD, FACR, FACRO; NYU Langone Health
• Study Chair: James N. Endicott, MD, PA; H. Lee Moffitt Cancer Center and Research Institute
• Study Chair: Julie A. Kish, MD, FACP; Josephine Ford Cancer Center

• PRS Account: Radiation Therapy Oncology Group
• Verification Date: January 2014