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Phase 3 N=940 Randomized Treatment

Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Head and Neck Cancer

Enrolled (actual)
940
Serious AEs
49.9%
Results posted
Dec 2017
Primary outcome: Primary: Progression-free Survival (PFS) (3-year Rate Reported) — 61.2; 58.9 percentage of participants — p=0.76

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
cetuximab (Drug); cisplatin (Drug); Accelerated Fractionation by Concomitant Boost (Radiation); Intensity-modulated radiation therapy (Radiation)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Radiation Therapy Oncology Group
Primary completion
Jan 2011

Outcome Measures

OutcomeResultp-value
PRIMARY
Progression-free Survival (PFS) (3-year Rate Reported)
61.2; 58.9 0.76
SECONDARY
Overall Survival (OS) (3-year Rate Reported)
72.9; 75.8 0.32
SECONDARY
Local-regional Failure (LRF) (3-year Rate Reported)
19.9; 25.9 0.97
SECONDARY
Rate of Mucositis Toxicity ≥ Grade 3
33.3; 43.2
SECONDARY
Rate of Other Toxicity ≥ Grade 3 (Not Mucositis)
89.3; 91.9
SECONDARY
Rate of Patients Who Tolerated Treatment
84.8; 70.7
SECONDARY
Rate of Deaths ≤ 30 Days After Discontinuation of Protocol Treatment
1.8; 2.0
SECONDARY
Quality of Life as Measured by European Quality of Life Questionnaire (EQ-5D)
0.78; 0.77; 0.84; 0.84 0.74
SECONDARY
Quality of Life as Measured by Proportion of Patients With Performance Status Scale for Head and Neck Cancer (PSS-HN) Scores ≤ 50
0.80; 0.85; 0.37; 0.37; 0.62; 0.63 0.13
SECONDARY
Quality of Life as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-HN) at 12 Months
-0.41; -5.11 0.016 sig
SECONDARY
Correlation of Expression of Epidermal Growth Factor Receptor (EGFR) With PFS, OS, and LRF
63.5; 60.3; 76.7; 75.0; 21.7; 19.2 0.60
SECONDARY
Correlation of Pre-treatment Positron Emission Tomography (PET)/CT Maximum Standardized Uptake Value (SUVmax) With PFS, OS, and LRF
55.9; 85.3; 85.3; 91.2; 32.4; 11.8 0.01 sig
SECONDARY
2-year Nodal Relapse Rates in Clinical N2-3 Patients by Post-treatment PET/CT Finding and Nodal Response
3.9; 33.3; 16.7; 11.1

Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer. PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

Eligibility Criteria

Inclusion criteria

  • Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;
  • Selected stage III or IV disease (T2N2-3M0, T3-4 any N M0); Note: Patients with T1, any N, or T2N1 tumors are not eligible.
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
  • History/physical examination within 4 weeks prior to registration, including assessment of weight and weight loss in past 6 months and an examination by a Medical Oncologist;
  • Chest x-ray (or Chest CT scan or PET/CT scan) within 6 weeks prior to registration;
  • CT scan or MRI of the head and neck (of the primary tumor and neck nodes) or PET/CT scan within 6 weeks prior to registration; see Section 6.11 for details of PET scans. Note: A PET/CT can only be used instead of a CT scan or MRI if the CT is a high quality scan with contrast.
  • Left ejection fraction determined by echocardiogram and/or multiple gated acquisition (MUGA) technique within 12 weeks of registration;
  • Zubrod Performance Status 0-1;
  • Age > 18;
  • Adequate bone marrow function, defined as follows:
  • Absolute neutrophil count (ANC) > 1, 800 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study;
  • Platelets > 100, 000 cells/mm3 based upon complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study;
  • Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.)
  • Adequate hepatic function, defined as follows:
  • Bilirubin 12.5 mg/dl;
  • Glucose 250 mg/dl;
  • Magnesium 3 mg/dl;
  • Potassium 6 mmol/L;
  • Sodium 155 mmol/L
  • Pregnant or lactating women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • Prior allergic reaction to the study drug(s) involved in this protocol;
  • Prior therapy that specifically and directly targets the EGFR pathway;
  • Prior severe infusion reaction to a monoclonal antibody.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00265941). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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