Overview

This trial is active, not recruiting.

Conditions head and neck cancer, precancerous condition
Treatments cetuximab, cisplatin
Phase phase 3
Target EGFR
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date June 2011
End date June 2020
Trial size 706 participants
Trial identifier NCT01302834, CDR0000695731, NCI-2011-02638, RTOG-1016

Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. 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. 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. It is not yet known whether radiation therapy is more effective with cisplatin or cetuximab in treating oropharyngeal cancer.

PURPOSE: This phase III trial is studying radiation therapy with cisplatin or cetuximab to see how well it works in treating patients with oropharyngeal cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients undergo image-guided intensity-modulated radiation therapy (IMRT) once daily on days 1-4 and twice daily on day 5 weekly for 6 weeks. Patients also receive high-dose cisplatin IV over 1-2 hours on days 1 and 22.
cisplatin
Given IV
(Active Comparator)
Beginning 1 week prior to IMRT, patients receive cetuximab IV over 2 hours. Patients then receive cetuximab IV over 1 hour once weekly for 7 weeks. Patients undergo IMRT as in arm I.
cetuximab
Given IV

Primary Outcomes

Measure
Overall survival
time frame: From randomization to date of failure (death) or last follow-up. Analysis occurs after 219 failures have been reported.

Secondary Outcomes

Measure
Progression-free survival
time frame: From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs at the same time as the primary outcome.
Local-regional failure
time frame: From randomization to date of failure (local or regional progression) or distant progression or death or last follow-up. Analysis occurs at the same time as the primary outcome.
Distant metastasis
time frame: From randomization to date of failure (distant progression) or local or regional progression or death or last follow-up. Analysis occurs at the same time as the primary outcome.
Acute toxicities (CTCAE v. 4) and overall toxicity burden at end of treatment and at 1, 3, and 6 months after completion of treatment
time frame: From start of treatment to 6 months after end of treatment.
Late toxicities (CTCAE v. 4) at 1, 2, and 5 years
time frame: From 6 months after end of treatment to 5 years after end of treatment.
Second primary cancers
time frame: From randomization to date of failure (second primary cancer) or death or last follow-up. Analysis occurs at the same time as the primary outcome.
Pattern of failure
time frame: From randomization to date of local, regional or distant progression or death or last follow-up. Analysis occurs at the same time as the primary outcome.
Early deaths
time frame: From randomization to 30 days after end of treatment.
Feeding tube rate at 1 year
time frame: From randomization to 1 year.
EORTC QLC-C30 at baseline, end of treatment, 3, 6, and 12 months from end of treatment.
time frame: From randomziation to 1 year after end of treatment.
EORTC QLQ-H&N35 at baseline, end of treatment, 3, 6, and 12 months from end of treatment.
time frame: From randomization to 1 year after end of treatment.
PRO-CTCAE-H&N at baseline, end of treatment, 3, 6, and 12 months from end of treatment.
time frame: From randomization to 1 year after end of treatement.
EQ-5D at baseline, end of treatment, 3, 6, and 12 months from end of treatment.
time frame: From randomization to 1 year after end of treatment.
Work Status Questionnaire at baseline, end of treatment, 3, 6, and 12 months.
time frame: From randomization to 1 year after end of treatment.
Dental status at baseline, 12, 24, 60 and 120 months from end of treatment.
time frame: From randomization to 10 years after end of treatment.
Hearing quality of life outcomes as measured by the HHIA-S at baseline, end of treatment and at 3, 6, and 12 months from end of treatment.
time frame: From randomization to 1 year after end of treatment.
Behavioral Risk Assessment Survey (BRASS) at baseline.
time frame: Prior to randomization.
Translational research analysis
time frame: From randomization to date of death or last follow-up.

Eligibility Criteria

Male or female participants from 18 years up to 120 years old.

DISEASE CHARACTERISTICS: - Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls) - No cancer from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal, or lip), nasopharynx, hypopharynx, or larynx, even if p16 positive - No carcinoma of the neck of unknown primary site origin (even if p16 positive) - Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx - Clinical evidence should be documented; may consist of palpation, imaging, or endoscopic evaluation; and should be sufficient to estimate the size of the primary (for T stage) - No distant metastasis or adenopathy below the clavicles - Patients must be positive for p16, determined by the OSU Innovation Center CLIA lab prior to step 2 registration (randomization) - Paraffin-embedded cytology specimens are acceptable for p16 evaluation, but cytology smears are not - Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations - Tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site - Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as non-therapeutic nodal excisions - Fine-needle aspirations of the neck are insufficient due to limited tissue for retrospective central review - Biopsy specimens from the primary or nodes measuring at least 3-5 mm are required - Clinical stage T1-2 N2a-N3 or T3-4 any N, including no distant metastases - No clinical stage T1-2 N0-1 - No simultaneous primaries or bilateral tumors PATIENT CHARACTERISTICS: - Zubrod performance status 0-1 - ANC ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable) - Bilirubin ≤ 2 mg/dL - AST or ALT ≤ 3 times upper limit of normal - Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min - Negative pregnancy test - Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study, and until at least 60 days following the last study treatment - Patients who are HIV-positive and have no prior AIDS-defining illness and have CD4 cells of at least 340/mm³ are eligible - HIV status must be known prior to registration - No multidrug resistance for HIV infection - Not seropositive for hepatitis B (hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or hepatitis C (anti-hepatitis C antibody positive) - Immunity to hepatitis B (anti-hepatitis B surface antibody positive) allowed - No prior invasive malignancy except non-melanoma skin cancer, or malignancy for which the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix) - No severe, active co-morbidity, defined as any of the following: - Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration - Transmural myocardial infarction within the last 6 months - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration - Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects - Laboratory tests for liver function and coagulation parameters are not required for entry into this protocol - Immunocompromised patients - No prior allergic reaction to cisplatin or cetuximab PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No prior systemic chemotherapy for the study cancer - Prior chemotherapy for a different cancer allowed - No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields - No prior cetuximab or other anti-EGFR therapy - No concurrent amifostine as a radioprotector - No concurrent granulocyte colony-stimulating factor or erythropoietin

Additional Information

Official title Phase III Trial of Radiotherapy Plus Cetuximab Versus Chemoradiotherapy in HPV-Associated Oropharynx Cancer
Principal investigator Andy M. Trotti, MD
Description OBJECTIVES: Primary - To determine whether substitution of cisplatin with cetuximab will result in comparable 5-year overall survival. Secondary - To monitor and compare progression-free survival for "safety". - To compare patterns of failure (locoregional vs distant). - To compare acute toxicity profiles (and overall toxicity burden). - To compare overall quality of life (QOL) short-term (< 6 months) and long-term (2 years). - To compare QOL Swallowing Domains short-term and long-term. - To compare clinician-reported versus patient-reported CTCAE toxicity events. - To explore differences in the cost effectiveness of cetuximab as compared to cisplatin. - To explore differences in work status and time to return to work. - To compare patient-reported changes in hearing. - To compare CTCAE v. 4 late toxicity at 1, 2, and 5 years. - To evaluate the effect of tobacco exposure (and other exposures) as measured by standardized computer-assisted self interview (CASI) on overall survival and progression-free survival. - To pilot CASI collection of patient reported outcomes in a cooperative group setting. - To determine whether specific molecular profiles are associated with overall or progression-free survival. - To investigate associations between changes in serum biomarkers or HPV-specific cellular immune responses measured at baseline and three months with overall or progression-free survival. OUTLINE: This is a multicenter study. Patients are stratified according to T stage (T1-2 vs T 3-4), N stage (N0-2a vs N2b-3), Zubrod performance status (0 vs 1), and smoking history (≤ 10 pack-years vs > 10 pack-years). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients undergo image-guided intensity-modulated radiation therapy (IMRT) once daily on days 1-4 and twice daily on day 5 weekly for 6 weeks. Patients also receive high-dose cisplatin IV over 1-2 hours on days 1 and 22. - Arm II: Beginning 1 week prior to IMRT, patients receive cetuximab IV over 2 hours. Patients then receive cetuximab IV over 1 hour once weekly for 7 weeks. Patients undergo IMRT as in arm I. Tumor tissue and blood samples are collected at baseline and may also be collected at 3- and 6-month follow-up visits for correlative studies. Patients may complete quality-of-life questionnaires and risk factors for head and neck cancer surveys at baseline, periodically during study, and at follow-up for 1 year. After completion of study therapy, patients are followed up at 1-3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.