De-intensification of Radiation and Chemotherapy for Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by UNC Lineberger Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01530997
First received: January 20, 2012
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Radiation: Intensity Modulated Radiotherapy (IMRT)
Drug: Cisplatin
Procedure: Limited surgical evaluation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Local control rate [ Time Frame: 2 years post-CRT ] [ Designated as safety issue: No ]
  • Regional control rate [ Time Frame: 2 years post-CRT ] [ Designated as safety issue: No ]
  • Local-regional control rate [ Time Frame: 2 years post-CRT ] [ Designated as safety issue: No ]
  • Cause-specific survival rate [ Time Frame: 2 years post-CRT ] [ Designated as safety issue: No ]
  • Overall survival rate [ Time Frame: 2 years post-CRT ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Speech and swallowing function [ Time Frame: Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: November 2011
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: De-escalated Radiation and Chemotherapy
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.
Radiation: 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).
Drug: 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.
Procedure: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01530997

Contacts
Contact: Bhishamjit Chera, MD (919) 966-7700 bchera@med.unc.edu
Contact: Rebecca Green, MSW (919) 445-5241 rlgreen@med.unc.edu

Locations
United States, Colorado
Penrose Cancer Center Recruiting
Colorado Springs, Colorado, United States, 80907
Contact: Alan Monroe, MD    719-776-5281    AlanMonroe@centura.org   
Contact: Julie Bergsten, RN, BSN    (719) 776-6045    JulieBergsten@centura.org   
Principal Investigator: Alan Monroe, MD         
United States, Florida
University of Florida, Department of Radiation Oncology Recruiting
Gainesville, Florida, United States, 32610-0385
Contact: Robert Amdur, MD    352-265-0287    amdurr@shands.ufl.edu   
Contact: Rebecca Beaulieu, MS    (352) 265-0680 ext 87818    schmir@shands.ufl.edu   
Principal Investigator: Robert Amdur, MD         
United States, North Carolina
University of North Carolina at Chapel Hill, Department of Radiation Oncology Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Bhishamjit Chera, MD    919-966-7700    bchera@med.unc.edu   
Contact: Rebecca Green, MSW    (919) 445-5241    rlgreen@med.unc.edu   
Principal Investigator: Bhishamjit Chera, MD         
Rex Healthcare Recruiting
Raleigh, North Carolina, United States, 27607
Contact: Justin Wu, MD    919-784-1251    justin.wu@rexhealth.com   
Contact: Lois Blausey, RN    919-784-6763    lois.blausey@rexhealth.com   
Principal Investigator: Justin Wu, MD         
Rex Cancer Center of Wakefield Recruiting
Raleigh, North Carolina, United States, 27614
Contact: Roger F Anderson, MD    919-570-7550    roger.anderson@rexhealth.com   
Contact: Anderson Black, RN    919-570-7630    anderson.black@rexhealth.com   
Principal Investigator: Roger F Anderson, MD         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Bhishamjit Chera, MD University of North Carolina, Chapel Hill
  More Information

Publications:
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01530997     History of Changes
Other Study ID Numbers: LCCC1120
Study First Received: January 20, 2012
Last Updated: September 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Human Papilloma Virus
Oropharynx
Oropharyngeal Squamous Cell Carcinoma
Squamous Cell Carcinoma
Radiation Therapy
Chemotherapy
p16

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014