Back to results

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

Primary Purpose

Carcinoma, Squamous Cell, Head and Neck Neoplasms, Oropharyngeal Neoplasms

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Intensity Modulated Radiotherapy (IMRT)

Cisplatin

Limited surgical evaluation

About this trial

This is an interventional treatment trial for Carcinoma, Squamous Cell focused on measuring Human Papilloma Virus, Oropharynx, Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma, Radiation Therapy, Chemotherapy, p16

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 18 years of age
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 > 5 years of abstinence from smoking
History/physical examination within 8 weeks prior to registration
Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to registration.
The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
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.
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.
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.
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.
Known HIV positive
Significant pre-existing hearing loss, as defined by the patient or treating physician.

Sites / Locations

Penrose Cancer Center
University of Florida, Department of Radiation Oncology
University of North Carolina at Chapel Hill, Department of Radiation Oncology
Rex Healthcare
Rex Cancer Center of Wakefield

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

De-escalated Radiation and Chemotherapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Pathologic Complete Response Rate After De-escalated CRT in HPV-positive and/or p16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC).

Pathologic Complete Response Rate is defined as no evidence of residual viable cancer in the evaluated pathological specimens.

Secondary Outcome Measures

Two-Year Local Control

Local control is the arrest of cancer growth at the site of origin.

Regional Control

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

Cause-specific survival is the percentage of participants who have not died from low-risk low-risk OPSCC.

Distant Metastases Free Survival

Distant metastases free survival is the percentage of subjects in a study who have survived without cancer spread.

Overall Survival Rate

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

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

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

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

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.

Full Information

NCT ID

NCT01530997

First Posted

January 20, 2012

Last Updated

December 7, 2021

Sponsor

UNC Lineberger Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT01530997

Brief Title

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

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

February 7, 2012 (Actual)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2019 (Actual)

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 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.

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 Papilloma Virus, 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

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

De-escalated Radiation and Chemotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Intensity Modulated Radiotherapy (IMRT)

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

Platinol

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Limited surgical evaluation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Pathologic Complete Response Rate After De-escalated CRT in HPV-positive and/or p16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC).

Description

Pathologic Complete Response Rate is defined as no evidence of residual viable cancer in the evaluated pathological specimens.

Time Frame

6 to 14 weeks after the last patient is enrolled, or approximately 24 to 32 months after study being opened

Secondary Outcome Measure Information:

Title

Two-Year Local Control

Description

Local control is the arrest of cancer growth at the site of origin.

Time Frame

Median follow-up was 36 months with a range of 5-53 months

Title

Regional Control

Description

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.

Time Frame

Median follow-up was 36 months with a range of 5-53 months

Title

Cause-Specific Survival

Description

Cause-specific survival is the percentage of participants who have not died from low-risk low-risk OPSCC.

Time Frame

The median follow-up was 36 months with a range of 5-53 months

Title

Distant Metastases Free Survival

Description

Distant metastases free survival is the percentage of subjects in a study who have survived without cancer spread.

Time Frame

the median follow-up was 36 months with a range of

Title

Overall Survival Rate

Description

The percentage of participants who are still alive from the start of treatment.

Time Frame

Median follow-up was 36 months with a range of 5-53 months.

Title

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N-35

Description

Time Frame

Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT

Title

European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status/QoL

Description

Time Frame

Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT

Title

The Eating Assessment Tool (EAT-10) Composite Score

Description

Time Frame

Prior to CRT, 4-8 weeks after CRT, follow-up visits for 2 years after CRT

Title

The Rosenbek Penetration Aspiration Scale

Description

Time Frame

Prior to CRT and 4-8 weeks after completion of CRT

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ≥ 18 years of age 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 > 5 years of abstinence from smoking History/physical examination within 8 weeks prior to registration Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to registration. The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 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. 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. 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. 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. Known HIV positive Significant pre-existing hearing loss, as defined by the patient or treating physician.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bhishamjit Chera, MD

Organizational Affiliation

University of North Carolina, Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

Penrose Cancer Center

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80907

Country

United States

Facility Name

University of Florida, Department of Radiation Oncology

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610-0385

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

Rex Healthcare

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27607

Country

United States

Facility Name

Rex Cancer Center of Wakefield

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27614

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20530316

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.

Results Reference

background

PubMed Identifier

28712533

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.

Results Reference

derived

PubMed Identifier

26581135

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.

Results Reference

derived

Links:

URL

https://clinicaltrials.gov/ct2/show/NCT01530997?term=LCCC1120&rank=1

Description

Clinical trial summary from the National Cancer Institute's PDQ® database

Learn more about this trial

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

We'll reach out to this number within 24 hrs