Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck
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|ClinicalTrials.gov Identifier: NCT00084318|
Recruitment Status : Completed
First Posted : June 11, 2004
Results First Posted : November 22, 2016
Last Update Posted : February 17, 2017
RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in 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. Cisplatin and docetaxel may make the tumor cells more sensitive to radiation therapy. Combining a monoclonal antibody with chemoradiotherapy and giving them after surgery may kill any remaining tumor cells.
PURPOSE: This randomized phase II trial is studying adjuvant cetuximab given together with chemoradiotherapy using cisplatin to see how well it works compared to adjuvant cetuximab given together with chemoradiotherapy using docetaxel in treating patients with resected stage III or stage IV squamous cell carcinoma (cancer) or lymphoepithelioma of the head and neck.
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Cancer||Biological: cetuximab Drug: cisplatin Drug: docetaxel Radiation: radiation therapy||Phase 2|
- Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin.
- Compare the safety and efficacy of these regimens in these patients.
- Compare locoregional control and overall survival rates in patients treated with these regimens.
- Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk [i.e., ≥ 2 positive nodes or extracapsular nodal extension]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7).
- Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7).
Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||238 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck|
|Study Start Date :||April 2004|
|Actual Primary Completion Date :||March 2009|
|Actual Study Completion Date :||December 2016|
U.S. FDA Resources
Experimental: RT + cisplatin + cetuximab
Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.
400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.Drug: cisplatin
30 mg/m^2 intravenously infused over over 60 minutes in weeks 2 through 7.Radiation: radiation therapy
60 Gy (2 Gy once a day, 5 times a week)
Experimental: RT + docetaxel + cetuximab
Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.Drug: docetaxel
15 mg/m^2 intravenously infused over 30 minutes in weeks 2 through 7.Radiation: radiation therapy
60 Gy (2 Gy once a day, 5 times a week)
- Disease-free Survival [ Time Frame: From randomization to 2 years ]Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.
- Overall Survival [ Time Frame: From randomization to 2 years ]Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).
- Treatment Tolerance [ Time Frame: From start of treatment to end of treatment (protocol treatment lasts seven weeks). ]Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.
- Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4) [ Time Frame: From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis. ]Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was >30%. [RTOG = Radiation Therapy Oncology Group]
- Frequency of Other Acute and Late Toxicity [ Time Frame: From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis. ]Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.
- Local-regional Control [ Time Frame: From randomization to 2 years ]Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).
- Correlation of EGFR (Total and Phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and Cyclin B1 Expression With Local-regional Control, and Overall and Disease-free Survival [ Time Frame: From randomization to two years ]Biomarker data has not yet been obtained and therefore this outcome measure cannot yet be reported.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00084318
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|Principal Investigator:||Paul M. Harari, MD||University of Wisconsin, Madison|
|Study Chair:||Merrill S. Kies, MD||M.D. Anderson Cancer Center|
|Study Chair:||Jeffrey N. Myers, MD, PhD, FACS||M.D. Anderson Cancer Center|