De-intensification of Radiation & Chemotherapy in Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Ca

Phase 2

Completed

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

• Registration Number: NCT01530997
• 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 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.

Study Timeline

• Study First Submitted: 2012-01-20
• Study Start: 2012-02-07
• Study First Submitted QC: 2012-02-07
• Study First Posted: 2012-02-10
• Primary Completion: 2014-11
• Results First Submitted: 2017-03-30
• Results First Submitted QC: 2017-07-10
• Results First Posted: 2017-08-09
• Study Completion: 2019-11
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-11
• Last Update Posted: 2024-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
De-escalated Radiation and Chemotherapy	Intensity Modulated Radiotherapy (IMRT)	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.
De-escalated Radiation and Chemotherapy	Limited surgical evaluation	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.
De-escalated Radiation and Chemotherapy	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Pathologic Complete Response Rate After De-escalated CRT in HPV-positive and/or p16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC).	6 to 14 weeks after the last patient is enrolled, or approximately 24 to 32 months after study being opened	Pathologic Complete Response Rate is defined as no evidence of residual viable cancer in the evaluated pathological specimens.

Secondary Outcome Measures

Name	Time	Method
Two-Year Local Control	Median follow-up was 36 months with a range of 5-53 months	Local control is the arrest of cancer growth at the site of origin.
Regional Control	Median follow-up was 36 months with a range of 5-53 months	Regional control is the percentage of participants who displayed control of cancer in sites that represent the first stages of spread from the local origin.
Overall Survival Rate	Median follow-up was 36 months with a range of 5-53 months.	The percentage of participants who are still alive from the start of treatment.
Cause-Specific Survival	The median follow-up was 36 months with a range of 5-53 months	Cause-specific survival is the percentage of participants who have not died from low-risk low-risk OPSCC.
Distant Metastases Free Survival	the median follow-up was 36 months with a range of	Distant metastases free survival is the percentage of subjects in a study who have survived without cancer spread.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N-35	Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT	The head \& neck cancer module of the EORTC QLQ comprises 35 questions assessing symptoms and side effects of treatment, social function and body image/sexuality.; The head \& neck cancer module incorporates seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech, social eating, social contact and sexuality. There are also eleven single items. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); several single item questions (Pain killers, nutritional supplements, feeding tube, weight loss, and weight gain) were just coded as no=1, yes=2. The scores of these scales were averaged from the scores of the component items, transformed and analyzed on a 0 - 100 scale. For all items and scales, high scores indicate more problems (i.e. there are no function scales in which high scores would mean better functioning).
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status/QoL	Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT	The EORTC QLQ-C30 is a cancer-specific instrument with 30 questions which incorporates 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). The scores of these scales were averaged from the scores of the component items, transformed and analyzed on a 0 - 100 scale. A higher score=better level of functioning or greater degree of symptoms.
The Eating Assessment Tool (EAT-10) Composite Score	Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT	The EAT-10 is a 10 item, validated self-administered instrument for documenting dysphagia severity. This questionnaire uses symptom-specific scores to assess dysphasia with solids, liquids, and pills as well as the impact of dysphagia on mental, social, and physical health. Higher raw scores represent worse QoL. All items have a 0-4 scale where 0 represents no problem and 4 represents severe problem. Total score can range from 0 to 40.
The Rosenbek Penetration Aspiration Scale	Prior to CRT and 4-8 weeks after completion of CRT	The Rosenbek Penetration Aspiration Scale will be used to quantify dysphagia. It is an 8-point, equal-appearing interval scale to describe penetration and aspiration events. The measure was used for thin substances, pureed substances, and solid substances.; 1. Material does not enter airway 2. Material enters the airway, remains above the vocal folds, and is ejected from the airway. 3. Material enters the airway, remains above the vocal folds, and is not ejected from the airway. 4. Material enters the airway, contacts the vocal folds, and is ejected from the airway. 5. Material enters the airway, contacts the vocal folds, and is not ejected from the airway. 6.Material enters the airway, passes below the vocal folds, and is ejected into the larynx or out of the airway. 7. Material enters the airway, passes below the vocal folds, and is not ejected from the trachea despite effort. 8. Material enters the airway, passes below the vocal folds, and no effort is made to eject.

Trial Locations

Locations (5)

University of Florida, Department of Radiation Oncology; 🇺🇸 Gainesville, Florida, United States

Penrose Cancer Center; 🇺🇸 Colorado Springs, Colorado, United States

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

Rex Cancer Center of Wakefield; 🇺🇸 Raleigh, North Carolina, United States

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