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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01530997
Recruitment Status : Active, not recruiting
First Posted : February 10, 2012
Results First Posted : August 9, 2017
Last Update Posted : March 9, 2020
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE January 20, 2012
First Posted Date  ICMJE February 10, 2012
Results First Submitted Date  ICMJE March 30, 2017
Results First Posted Date  ICMJE August 9, 2017
Last Update Posted Date March 9, 2020
Actual Study Start Date  ICMJE February 7, 2012
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2017)
Pathologic Complete Response Rate After De-escalated CRT in HPV-positive and/or p16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC). [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2012)
Complete pathological response rate after de-escalated CRT in HPV-positive and/or p16 positive OPSCC. [ Time Frame: 6 to 14 weeks after the last patient is enrolled, or approximately 24 to 32 months after study being opened ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2017)
  • Two-Year Local Control [ Time Frame: 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 [ Time Frame: 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.
  • Cause-Specific Survival [ Time Frame: 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 [ Time Frame: 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.
  • Overall Survival Rate [ Time Frame: 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.
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N-35 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2012)
  • Local control rate [ Time Frame: 2 years post-CRT ]
  • Regional control rate [ Time Frame: 2 years post-CRT ]
  • Local-regional control rate [ Time Frame: 2 years post-CRT ]
  • Cause-specific survival rate [ Time Frame: 2 years post-CRT ]
  • Overall Survival Rate [ Time Frame: 2 years post-CRT ]
  • Head and neck quality of life assessments [ Time Frame: Prior to CRT, weekly during CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT ]
  • Speech and swallowing function [ Time Frame: Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE De-intensification of Radiation & Chemotherapy in Low-Risk Human Papillomavirus-related Oropharyngeal Squamous Cell Ca
Official Title  ICMJE Phase II Study of De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms
  • Oropharyngeal Neoplasms
Intervention  ICMJE
  • Radiation: Intensity Modulated Radiotherapy (IMRT)
    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).
  • Drug: Cisplatin
    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.
    Other Name: Platinol
  • Procedure: Limited surgical evaluation
    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.
Study Arms  ICMJE Experimental: De-escalated Radiation and Chemotherapy
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.
Interventions:
  • Radiation: Intensity Modulated Radiotherapy (IMRT)
  • Drug: Cisplatin
  • Procedure: Limited surgical evaluation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 10, 2017)
45
Original Estimated Enrollment  ICMJE
 (submitted: February 7, 2012)
40
Estimated Study Completion Date  ICMJE January 2022
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01530997
Other Study ID Numbers  ICMJE LCCC 1120
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UNC Lineberger Comprehensive Cancer Center
Study Sponsor  ICMJE UNC Lineberger Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bhishamjit Chera, MD University of North Carolina, Chapel Hill
PRS Account UNC Lineberger Comprehensive Cancer Center
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP