Overview

This trial is active, not recruiting.

Conditions carcinoma, squamous cell, head and neck neoplasms, oropharyngeal neoplasms
Treatments intensity modulated radiotherapy (imrt), cisplatin, limited surgical evaluation
Phase phase 2
Sponsor UNC Lineberger Comprehensive Cancer Center
Start date November 2011
End date November 2014
Trial size 43 participants
Trial identifier NCT01530997, LCCC 1120

Summary

The purpose of this research study is to learn about the effectiveness of using lower-intensity radiation and chemotherapy to treat human papillomavirus (HPV) associated low-risk oropharyngeal and/or unknown primary squamous cell carcinomas of the head and neck. The cure rate for this type of cancer is estimated to be high, > 90%. The standard treatment for this cancer is 7 weeks of radiation with 3 high doses of cisplatin. Sometimes surgery is performed afterwards. This standard regimen causes a lot of side effects and long term complications. This study is evaluating whether a lower dose of radiation and chemotherapy may provide a similar cure rate as the longer, more intensive standard regimen. Patients in this study will receive 1 less week of radiation and a lower weekly dose of chemotherapy followed by a limited surgical evaluation.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients will receive 54 to 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) will be obtained 4 to 8 weeks after completion of CRT to assess response. All patients will have surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there is no evidence of residual tumor and will undergo a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT.
intensity modulated radiotherapy (imrt)
All patients will receive IMRT. Dose painting IMRT will be used and all doses will be specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) will be treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR will be 2 Gy per day and 1.8 Gy per day, respectively. The PTV-HR will include the gross tumor and the PTV-SR will include the lymph nodes at risk for harboring micro-metastatic disease (i.e. subclinical disease).
cisplatin
Cisplatin, 30mg/m2, will be given intravenously over 60 minutes weekly during IMRT; 6 total doses for a total of 180 mg/m2. It is preferred that the doses be administered on days 1, 8, 15, 22, and 29, and 36 of IMRT; however, this is not mandatory.
limited surgical evaluation
4 to 14 weeks after completion of CRT, patients will have at least a biopsy of the primary tumor and limited neck surgery to remove those lymph nodes that were involved with cancer prior to CRT.

Primary Outcomes

Measure
Complete pathological response rate after de-escalated CRT in HPV-positive and/or p16 positive OPSCC.
time frame: 6 to 14 weeks after the last patient is enrolled, or approximately 24 to 32 months after study being opened

Secondary Outcomes

Measure
Local control rate
time frame: 2 years post-CRT
Regional control rate
time frame: 2 years post-CRT
Local-regional control rate
time frame: 2 years post-CRT
Cause-specific survival rate
time frame: 2 years post-CRT
Overall survival rate
time frame: 2 years post-CRT
Head and neck quality of life assessments
time frame: Prior to CRT, weekly during CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT
Speech and swallowing function
time frame: Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. ≥ 18 years of age 2. T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx 3. Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive 4. ≤ 10 pack-years smoking history or > 5 years of abstinence from smoking 5. History/physical examination within 8 weeks prior to registration 6. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to registration. 7. ECOG Performance Status 0-1 8. CBC/differential obtained within 4 weeks prior to registration, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl. 9. Adequate renal and hepatic function within 4 weeks prior to registration, defined as follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional ULN; AST or ALT < 3 x the institutional ULN. 10. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential. 11. Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment. 12. Patients must be deemed able to comply with the treatment plan and follow-up schedule. 13. Patients must provide study specific informed consent prior to study entry. Exclusion Criteria: 1. Prior history of radiation therapy to the head and neck 2. Prior history of head and neck cancer. 3. Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; Transmural myocardial infarction within the last 6 months; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; Note, however, coagulation parameters are not required for entry into this protocol; Pre-existing ≥ grade 2 neuropathy; Prior organ transplant. 4. Known HIV positive 5. Significant pre-existing hearing loss, as defined by the patient or treating physician.

Additional Information

Official title Phase II Study of De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
Principal investigator Bhishamjit Chera, MD
Description The aim is to evaluate the pathological response rate of HPV positive and/or p16 positive low-risk oropharyngeal squamous cell carcinoma (OPSCC) after de-intensified chemoradiotherapy (CRT). Patients will receive 54 to 60 Gy of Intensity Modulated Radiotherapy (IMRT) with concurrent weekly intravenous cisplatin (30 mg/m2). Diagnostic imaging (CT and/or MRI) will be obtained 4 to 8 weeks after completion of CRT to assess response. All patients will have surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there is no evidence of residual tumor and will undergo a limited neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, 4 to 14 weeks after CRT. The primary endpoint of this study is the rate of pathological complete response (pCR) after CRT. Longitudinal assessments of quality of life and patient reported outcomes will be obtained prior to, during, and after CRT.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by UNC Lineberger Comprehensive Cancer Center.