Back to resultsDe-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study
Primary Purpose
Carcinoma, Squamous Cell, Head and Neck Neoplasms, Oropharyngeal Neoplasms
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Intensity Modulated Radiotherapy (IMRT)
Cisplatin (or alternative)
Assessment for surgical evaluation
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Squamous Cell focused on measuring Human Papillomavirus, Oropharynx, Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma, Radiation Therapy, Chemotherapy, p16
Eligibility Criteria
Inclusion Criteria:
- ≥ 18 years of age (no upper age limit)
- 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 ≤ 30 pack-years smoking history WITH ≥ 5 years abstinence from smoking
- Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
- ECOG Performance Status 0-1
- CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows: 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 ULN; AST or 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
Exclusion Criteria:
- Prior history of radiation therapy to the head and neck
- Prior history of head and neck cancer.
- Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
- Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
- 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; Systemic lupus; Psoriatic arthritis.
- Known HIV positive.
Sites / Locations
- University of Florida
- University of North Carolina at Chapel Hill, Department of Radiation Oncology
- Pardee Memorial Hospital
- High Point Regional Health
- Rex Healthcare
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
De-escalated Radiation and Chemotherapy
Arm Description
Patients will receive Intensity Modulated Radiotherapy Treatments (IMRT), 60 Gy at 2 Gy/fx. The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history. Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.
Outcomes
Primary Outcome Measures
2 Year Progression Free Survival After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Progression Free Survival (PFS) was defined as the time from the beginning of treatment to cancer progression or death. The outcome measure will be reported as the proportion of patients with PFS at 2 years post-treatment.
Secondary Outcome Measures
2 Year Local Control (LC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with LC at 2 years post-treatment.
2 Year Regional Control (RC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with RC at 2 years post-treatment.
2 Year Local-regional Control (LRC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with LRC at 2 years post-treatment.
2 Year Distant Metastasis Free Survival (DMFS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with DMFS at 2 years post-treatment.
2 Year Overall Survival (OS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients who are still alive (overall survival) at 2 years post-treatment.
Head and Neck Quality of Life Assessments
Speech and Swallowing Function
Full Information
NCT ID
NCT02281955
First Posted
October 3, 2014
Last Updated
March 3, 2023
Sponsor
UNC Lineberger Comprehensive Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT02281955
Brief Title
De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study
Official Title
De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 2014 (Actual)
Primary Completion Date
November 2019 (Actual)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
The proposed study is a follow-up study to NCT01530997. In NCT01530997, patients with HPV positive and/or p16 positive low-risk oropharyngeal squamous cell carcinoma (OPSCC) received de-intensified chemoradiotherapy (CRT) followed by a limited surgical evaluation. The primary endpoint of NCT01530997 was the rate of pathological complete response (pCR) after CRT. Power computations were performed for N=40 and were based on the null hypothesis (H0) that the pCR for de-intensified chemoradiotherapy is at least 87%, the historical rate. The type 1 error for this calculation was 14.2%. 43 patients enrolled and 38 were evaluable for the primary endpoint. The observed pCR rate was 89% (34/38). Since the observed pCR rate was excellent in NCT01530997 and was in concordance with the expected rate, in the proposed study we will not mandate a post-CRT surgical evaluation. Instead a PET/CT 10 to 16 weeks post-CRT will be used to determine whether a surgical evaluation is needed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Squamous Cell, Head and Neck Neoplasms, Oropharyngeal Neoplasms
Keywords
Human Papillomavirus, Oropharynx, Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma, Radiation Therapy, Chemotherapy, p16
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
115 (Actual)
8. Arms, Groups, and Interventions
Arm Title
De-escalated Radiation and Chemotherapy
Arm Type
Experimental
Arm Description
Patients will receive Intensity Modulated Radiotherapy Treatments (IMRT), 60 Gy at 2 Gy/fx. The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history. Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.
Intervention Type
Radiation
Intervention Name(s)
Intensity Modulated Radiotherapy (IMRT)
Intervention Description
All patients will receive Intensity Modulated Radiotherapy Treatments (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 areas at risk for harboring subclinical microscopic disease.
Intervention Type
Drug
Intervention Name(s)
Cisplatin (or alternative)
Intervention Description
Cisplatin is the preferred mandated first choice chemotherapy, however alternative weekly regimens are permissible. Justification for not using cisplatin must be documented. Chemotherapy will be given intravenously weekly during IMRT. 6 total doses will be given. It is preferred that the doses be administered on days 1, 8, 15, 22, 29, and 36; however, this is not mandatory. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history.
Intervention Type
Procedure
Intervention Name(s)
Assessment for surgical evaluation
Intervention Description
Decisions for surgical evaluation will be based on the results of the PET/CT 10 to 16 weeks after CRT and clinical exam (including fiberoptic laryngoscopy) at that time. Other optional imaging studies may be performed. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon, with the goal being to remove any suspected residual tumor with a negative resection margin while maintaining organ preservation. This may include biopsies and/or oncological resections of the primary tumor and lymph node metastases. Patients with a negative PET/CT scan will be observed.
Primary Outcome Measure Information:
Title
2 Year Progression Free Survival After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Description
Progression Free Survival (PFS) was defined as the time from the beginning of treatment to cancer progression or death. The outcome measure will be reported as the proportion of patients with PFS at 2 years post-treatment.
Time Frame
Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks)
Secondary Outcome Measure Information:
Title
2 Year Local Control (LC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Description
The outcome measure will be reported as the proportion of patients with LC at 2 years post-treatment.
Time Frame
Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
Title
2 Year Regional Control (RC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Description
The outcome measure will be reported as the proportion of patients with RC at 2 years post-treatment.
Time Frame
Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
Title
2 Year Local-regional Control (LRC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Description
The outcome measure will be reported as the proportion of patients with LRC at 2 years post-treatment.
Time Frame
Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
Title
2 Year Distant Metastasis Free Survival (DMFS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Description
The outcome measure will be reported as the proportion of patients with DMFS at 2 years post-treatment.
Time Frame
Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
Title
2 Year Overall Survival (OS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Description
The outcome measure will be reported as the proportion of patients who are still alive (overall survival) at 2 years post-treatment.
Time Frame
Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
Title
Head and Neck Quality of Life Assessments
Time Frame
Within 2 weeks prior to CRT, weekly during CRT, 10-16 weeks after CRT, follow-up visits every 2 months after CRT for 2 years, then every 6 months for 3 years, then yearly, up to 10 years.
Title
Speech and Swallowing Function
Time Frame
Within 2 weeks prior to CRT, 6-8 weeks after CRT, 6 months after CRT (MBS); Within 2 weeks prior to CRT, 10-16 weeks after CRT, follow-up visits every 2 months after CRT for 2 years, then every 6 months for 3 years, then yearly (EAT-10), up to 10 years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥ 18 years of age (no upper age limit)
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 ≤ 30 pack-years smoking history WITH ≥ 5 years abstinence from smoking
Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
ECOG Performance Status 0-1
CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows: 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 ULN; AST or 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
Exclusion Criteria:
Prior history of radiation therapy to the head and neck
Prior history of head and neck cancer.
Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
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; Systemic lupus; Psoriatic arthritis.
Known HIV positive.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Colette Shen, MD
Organizational Affiliation
University of North Carolina at Chapel Hill, Department of Radiation Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of North Carolina at Chapel Hill, Department of Radiation Oncology
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Pardee Memorial Hospital
City
Hendersonville
State/Province
North Carolina
ZIP/Postal Code
28791
Country
United States
Facility Name
High Point Regional Health
City
High Point
State/Province
North Carolina
ZIP/Postal Code
27262
Country
United States
Facility Name
Rex Healthcare
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32017652
Citation
Chera BS, Kumar S, Shen C, Amdur R, Dagan R, Green R, Goldman E, Weiss J, Grilley-Olson J, Patel S, Zanation A, Hackman T, Blumberg J, Patel S, Thorp B, Weissler M, Yarbrough W, Sheets N, Mendenhall W, Tan XM, Gupta GP. Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer. J Clin Oncol. 2020 Apr 1;38(10):1050-1058. doi: 10.1200/JCO.19.02444. Epub 2020 Feb 4. Erratum In: J Clin Oncol. 2020 Oct 20;38(30):3579. J Clin Oncol. 2023 Sep 20;41(27):4449.
Results Reference
derived
PubMed Identifier
31411949
Citation
Chera BS, Amdur RJ, Green R, Shen C, Gupta G, Tan X, Knowles M, Fried D, Hayes N, Weiss J, Grilley-Olson J, Patel S, Zanation A, Hackman T, Zevallos J, Blumberg J, Patel S, Kasibhatla M, Sheets N, Weissler M, Yarbrough W, Mendenhall W. Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. J Clin Oncol. 2019 Oct 10;37(29):2661-2669. doi: 10.1200/JCO.19.01007. Epub 2019 Aug 14.
Results Reference
derived
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De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study
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