De-intensification of Radiation & Chemotherapy in Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Ca
Phase II Study of De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
1 other identifier
interventional
45
1 country
5
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2012
Longer than P75 for phase_2
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 20, 2012
CompletedStudy Start
First participant enrolled
February 7, 2012
CompletedFirst Posted
Study publicly available on registry
February 10, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedResults Posted
Study results publicly available
August 9, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2019
CompletedNovember 13, 2024
November 1, 2024
2.7 years
January 20, 2012
March 30, 2017
November 11, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Pathologic Complete Response Rate After De-escalated CRT in HPV-positive and/or p16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC).
Pathologic Complete Response Rate is defined as no evidence of residual viable cancer in the evaluated pathological specimens.
6 to 14 weeks after the last patient is enrolled, or approximately 24 to 32 months after study being opened
Secondary Outcomes (9)
Two-Year Local Control
Median follow-up was 36 months with a range of 5-53 months
Regional Control
Median follow-up was 36 months with a range of 5-53 months
Cause-Specific Survival
The median follow-up was 36 months with a range of 5-53 months
Distant Metastases Free Survival
the median follow-up was 36 months with a range of
Overall Survival Rate
Median follow-up was 36 months with a range of 5-53 months.
- +4 more secondary outcomes
Study Arms (1)
De-escalated Radiation and Chemotherapy
EXPERIMENTALPatients 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.
Interventions
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, 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.
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.
Eligibility Criteria
You may qualify if:
- ≥ 18 years of age
- T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx
- Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive
- ≤ 10 pack-years smoking history or \> 5 years of abstinence from smoking
- History/physical examination within 8 weeks prior to registration
- Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to registration.
- The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Complete Blood Count (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.
- 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 upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x the institutional ULN.
- Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential.
- Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
- Patients must be deemed able to comply with the treatment plan and follow-up schedule.
- Patients must provide study specific informed consent prior to study entry.
You may not qualify if:
- Prior history of radiation therapy to the head and neck
- Prior history of head and neck cancer.
- 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.
- Known HIV positive
- Significant pre-existing hearing loss, as defined by the patient or treating physician.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Penrose Cancer Center
Colorado Springs, Colorado, 80907, United States
University of Florida, Department of Radiation Oncology
Gainesville, Florida, 32610-0385, United States
University of North Carolina at Chapel Hill, Department of Radiation Oncology
Chapel Hill, North Carolina, 27599, United States
Rex Healthcare
Raleigh, North Carolina, 27607, United States
Rex Cancer Center of Wakefield
Raleigh, North Carolina, 27614, United States
Related Publications (3)
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.
PMID: 20530316BACKGROUNDMavroidis P, Price A, Fried D, Kostich M, Amdur R, Mendenhall W, Liu C, Das S, Marks LB, Chera B. Dose-volume toxicity modeling for de-intensified chemo-radiation therapy for HPV-positive oropharynx cancer. Radiother Oncol. 2017 Aug;124(2):240-247. doi: 10.1016/j.radonc.2017.06.020. Epub 2017 Jul 13.
PMID: 28712533DERIVEDChera BS, Amdur RJ, Tepper J, Qaqish B, Green R, Aumer SL, Hayes N, Weiss J, Grilley-Olson J, Zanation A, Hackman T, Funkhouser W, Sheets N, Weissler M, Mendenhall W. Phase 2 Trial of De-intensified Chemoradiation Therapy for Favorable-Risk Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. Int J Radiat Oncol Biol Phys. 2015 Dec 1;93(5):976-85. doi: 10.1016/j.ijrobp.2015.08.033. Epub 2015 Aug 22.
PMID: 26581135DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Per the protocol, affiliate sites will only report grade 3/4 and all fatal (grade 5) toxicities. 1/2 toxicities were not reported for affiliate sites.
Results Point of Contact
- Title
- Robin V. Johnson
- Organization
- UNC Lineberger Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Bhishamjit Chera, MD
University of North Carolina, Chapel Hill
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 20, 2012
First Posted
February 10, 2012
Study Start
February 7, 2012
Primary Completion
November 1, 2014
Study Completion
November 1, 2019
Last Updated
November 13, 2024
Results First Posted
August 9, 2017
Record last verified: 2024-11