De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study

Phase 2

Completed

• Conditions: Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Head and Neck Neoplasms
• Interventions: Radiation: Intensity Modulated Radiotherapy (IMRT); Drug: Cisplatin (or alternative); Procedure: Assessment for surgical evaluation

• Registration Number: NCT02281955
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

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.

Study Timeline

• Study Start: 2014-08
• Study First Submitted: 2014-10-03
• Study First Submitted QC: 2014-10-30
• Study First Posted: 2014-11-04
• Primary Completion: 2019-11
• Results First Submitted: 2020-10-13
• Results First Submitted QC: 2020-12-01
• Results First Posted: 2020-12-22
• Study Completion: 2024-11-24
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2025-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 115

Inclusion Criteria

1. ≥ 18 years of age (no upper age limit)
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 ≤ 30 pack-years smoking history WITH ≥ 5 years abstinence from smoking
5. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
6. ECOG Performance Status 0-1
7. 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.
8. 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.
9. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential
10. Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
11. Patients must be deemed able to comply with the treatment plan and follow-up schedule.
12. 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. Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
4. Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
5. 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.
6. Known HIV positive.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
De-escalated Radiation and Chemotherapy	Cisplatin (or alternative)	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.
De-escalated Radiation and Chemotherapy	Assessment for surgical evaluation	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.
De-escalated Radiation and Chemotherapy	Intensity Modulated Radiotherapy (IMRT)	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.

Primary Outcome Measures

Name	Time	Method
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)	Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks)	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

Name	Time	Method
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)	Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).	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)	Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).	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)	Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).	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)	Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).	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)	Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).	The outcome measure will be reported as the proportion of patients who are still alive (overall survival) at 2 years post-treatment.

Trial Locations

Locations (5)

University of North Carolina at Chapel Hill, Department of Radiation Oncology; 🇺🇸 Chapel Hill, North Carolina, United States

Pardee Memorial Hospital; 🇺🇸 Hendersonville, North Carolina, United States

Rex Healthcare; 🇺🇸 Raleigh, North Carolina, United States

High Point Regional Health; 🇺🇸 High Point, North Carolina, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States