Clinical trial NCT01530997: De-intensification of Radiation & Chemotherapy in Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Ca
Official title: Phase II Study of De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Squamous Cell
Head and Neck Neoplasms
Oropharyngeal Neoplasms
Keywords: Human Papilloma Virus
Oropharynx
Oropharyngeal Squamous Cell Carcinoma
Squamous Cell Carcinoma
Radiation Therapy
Chemotherapy
p16
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2012-02-10
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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. The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
8. 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.
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 upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (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.

Primary outcomes:
measure: Pathologic Complete Response Rate After De-escalated CRT in HPV-positive and/or p16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC).
timeFrame: 6 to 14 weeks after the last patient is enrolled, or approximately 24 to 32 months after study being opened
Secondary outcomes:
measure: Two-Year Local Control
timeFrame: Median follow-up was 36 months with a range of 5-53 months
measure: Regional Control
timeFrame: Median follow-up was 36 months with a range of 5-53 months
measure: Cause-Specific Survival
timeFrame: The median follow-up was 36 months with a range of 5-53 months
measure: Distant Metastases Free Survival
timeFrame: the median follow-up was 36 months with a range of
measure: Overall Survival Rate
timeFrame: Median follow-up was 36 months with a range of 5-53 months.
measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N-35
timeFrame: Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT
measure: European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status/QoL
timeFrame: Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT
measure: The Eating Assessment Tool (EAT-10) Composite Score
timeFrame: Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT
measure: The Rosenbek Penetration Aspiration Scale
timeFrame: Prior to CRT and 4-8 weeks after completion of CRT
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Penrose Cancer Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida, Department of Radiation Oncology
state: Florida
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill, Department of Radiation Oncology
state: North Carolina
city: Raleigh
country: United States
facility: Rex Healthcare
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center of Wakefield
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Bhishamjit Chera, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Mavroidis 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.
citation: Chera 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.