Swallowing Outcomes and Circulating Tumor DNA in Patients With HPV Related Oropharyngeal Cancer Treated With Transoral Surgery and Reduced Intensity Adjuvant Therapy

NCT ID: NCT04920344

Last Updated: 2023-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-19

Study Completion Date

2025-05-08

Brief Summary

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This is a non-randomized, open-label phase II clinical trial that studies the effect of reduced dose radiation therapy and chemotherapy after surgery in treating patients with human papillomavirus (HPV) caused throat cancer. Giving reduced dose radiation therapy and chemotherapy after surgery may improve quality of life compared with standard of care primary chemoradiation approach without compromising survival.

Detailed Description

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PRIMARY OBJECTIVE:

I. To measure swallowing function and disease specific quality of life of patients with oropharyngeal cancer treated with transoral surgery and reduced intensity adjuvant therapy.

SECONDARY OBJECTIVES:

I. To examine kinetics of circulating tumor deoxyribonucleic acid (DNA) in patients treated with transoral surgery.

II. To estimate local control, progression free and overall survival using transoral surgery and reduced intensity adjuvant therapy.

OUTLINE: Based on pathologic findings after standard of care transoral surgery, patients are assigned to 1 of 3 groups.

GROUP I (LOW RISK): Patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.

GROUP II (MEDIUM RISK): Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) for 5 weeks in the absence of disease progression or unacceptable toxicity.

GROUP III (HIGH RISK): Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT for 6 weeks and receive cisplatin intravenously (IV) weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Conditions

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Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Oropharyngeal Human Papillomavirus-Positive Squamous Cell Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))

After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.

Group Type ACTIVE_COMPARATOR

Transoral Surgery

Intervention Type PROCEDURE

Patients will undergo transoral surgery

Incisional Tumor Biopsy

Intervention Type PROCEDURE

Incisional biopsy of the primary tumor site will be required to confirm p16/HPV status of the tumor

Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment

Intervention Type OTHER

Assess ctDNA levels at baseline, 2 weeks, 4 weeks, 10 weeks, 24 weeks and 1 year after the surgery.

MD Anderson Dysphagia Index

Intervention Type OTHER

MDADI is a 20 item quality of life questionnaire specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients. The total score ranges from 20 to 100 with the higher score indicating higher level of function.

University of Washington Quality of Life Questionnaire

Intervention Type OTHER

University of Washington Questionnaire is a 15 item quality of life instrument specifically designed for head and neck cancer patients.

Euro-QOL 5 dimension scale questionnaire

Intervention Type OTHER

A generic quality of life and cost utility instrument widely used and validated for multiple disease settings, including head and neck cancer.

Modified barium swallow (MBS) evaluation with aspiration-penetration scale

Intervention Type DIAGNOSTIC_TEST

The videofluoroscopic modified barium swallow (MBS) study is the gold standard for for the evaluation of dysphagia, and specifically, airway protective mechanisms.

The penetration/aspiration (PEN/ASP) scale is a routinely used eight-point scale designed to describe the depth of bolus penetration into the airway and the patient response to the penetration or aspiration.

GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)

Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Transoral Surgery

Intervention Type PROCEDURE

Patients will undergo transoral surgery

External Beam Radiation Therapy

Intervention Type RADIATION

Patients in Group II and Group III will undergo External Beam Radiation Therapy (EBRT) RT following transoral surgery.

Incisional Tumor Biopsy

Intervention Type PROCEDURE

Incisional biopsy of the primary tumor site will be required to confirm p16/HPV status of the tumor

Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment

Intervention Type OTHER

Assess ctDNA levels at baseline, 2 weeks, 4 weeks, 10 weeks, 24 weeks and 1 year after the surgery.

MD Anderson Dysphagia Index

Intervention Type OTHER

MDADI is a 20 item quality of life questionnaire specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients. The total score ranges from 20 to 100 with the higher score indicating higher level of function.

University of Washington Quality of Life Questionnaire

Intervention Type OTHER

University of Washington Questionnaire is a 15 item quality of life instrument specifically designed for head and neck cancer patients.

Euro-QOL 5 dimension scale questionnaire

Intervention Type OTHER

A generic quality of life and cost utility instrument widely used and validated for multiple disease settings, including head and neck cancer.

Modified barium swallow (MBS) evaluation with aspiration-penetration scale

Intervention Type DIAGNOSTIC_TEST

The videofluoroscopic modified barium swallow (MBS) study is the gold standard for for the evaluation of dysphagia, and specifically, airway protective mechanisms.

The penetration/aspiration (PEN/ASP) scale is a routinely used eight-point scale designed to describe the depth of bolus penetration into the airway and the patient response to the penetration or aspiration.

GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)

Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Transoral Surgery

Intervention Type PROCEDURE

Patients will undergo transoral surgery

External Beam Radiation Therapy

Intervention Type RADIATION

Patients in Group II and Group III will undergo External Beam Radiation Therapy (EBRT) RT following transoral surgery.

Cisplatin

Intervention Type DRUG

Patients in Group III will receive cisplatin, 30 mg/m2, administered intravenously weekly per for 6 weeks.

Incisional Tumor Biopsy

Intervention Type PROCEDURE

Incisional biopsy of the primary tumor site will be required to confirm p16/HPV status of the tumor

Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment

Intervention Type OTHER

Assess ctDNA levels at baseline, 2 weeks, 4 weeks, 10 weeks, 24 weeks and 1 year after the surgery.

MD Anderson Dysphagia Index

Intervention Type OTHER

MDADI is a 20 item quality of life questionnaire specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients. The total score ranges from 20 to 100 with the higher score indicating higher level of function.

University of Washington Quality of Life Questionnaire

Intervention Type OTHER

University of Washington Questionnaire is a 15 item quality of life instrument specifically designed for head and neck cancer patients.

Euro-QOL 5 dimension scale questionnaire

Intervention Type OTHER

A generic quality of life and cost utility instrument widely used and validated for multiple disease settings, including head and neck cancer.

Modified barium swallow (MBS) evaluation with aspiration-penetration scale

Intervention Type DIAGNOSTIC_TEST

The videofluoroscopic modified barium swallow (MBS) study is the gold standard for for the evaluation of dysphagia, and specifically, airway protective mechanisms.

The penetration/aspiration (PEN/ASP) scale is a routinely used eight-point scale designed to describe the depth of bolus penetration into the airway and the patient response to the penetration or aspiration.

Interventions

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Transoral Surgery

Patients will undergo transoral surgery

Intervention Type PROCEDURE

External Beam Radiation Therapy

Patients in Group II and Group III will undergo External Beam Radiation Therapy (EBRT) RT following transoral surgery.

Intervention Type RADIATION

Cisplatin

Patients in Group III will receive cisplatin, 30 mg/m2, administered intravenously weekly per for 6 weeks.

Intervention Type DRUG

Incisional Tumor Biopsy

Incisional biopsy of the primary tumor site will be required to confirm p16/HPV status of the tumor

Intervention Type PROCEDURE

Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment

Assess ctDNA levels at baseline, 2 weeks, 4 weeks, 10 weeks, 24 weeks and 1 year after the surgery.

Intervention Type OTHER

MD Anderson Dysphagia Index

MDADI is a 20 item quality of life questionnaire specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients. The total score ranges from 20 to 100 with the higher score indicating higher level of function.

Intervention Type OTHER

University of Washington Quality of Life Questionnaire

University of Washington Questionnaire is a 15 item quality of life instrument specifically designed for head and neck cancer patients.

Intervention Type OTHER

Euro-QOL 5 dimension scale questionnaire

A generic quality of life and cost utility instrument widely used and validated for multiple disease settings, including head and neck cancer.

Intervention Type OTHER

Modified barium swallow (MBS) evaluation with aspiration-penetration scale

The videofluoroscopic modified barium swallow (MBS) study is the gold standard for for the evaluation of dysphagia, and specifically, airway protective mechanisms.

The penetration/aspiration (PEN/ASP) scale is a routinely used eight-point scale designed to describe the depth of bolus penetration into the airway and the patient response to the penetration or aspiration.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Therapeutic Conventional Surgery EBRT Cisplatin Chemotherapy Circulating ctDNA levels assessment MDADI UW QOL questionnaire EQ-5D-5L MBS with PEN/ASP scale

Eligibility Criteria

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Inclusion Criteria

* Histologically proven squamous cell carcinoma of the oropharynx
* Clinical stage T1-2, N0-N3, M0 by American Joint Committee on Cancer (AJCC) 8 criteria
* Must have tumors deemed surgically resectable with acceptable morbidity
* Estimated life expectancy of at least 12 weeks
* Must give informed consent
* Must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
* Must have detectable circulating HPV DNA levels
* Platelets \>= 100,000/ul
* Absolute neutrophil count (ANC) \>= 1,500/ul
* Hemoglobin \> 8 g/dl (use of transfusion to achieve this is acceptable)
* Total bilirubin \< 2 X institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 3 X institutional ULN
* Serum creatinine \< 2 x institutional ULN or creatinine clearance \> 50 ml/min as determined by 24 hour collection or estimated by Cockcroft-Gault formula
* Negative pregnancy test, if applicable

Exclusion Criteria

* Patients may not have received previous therapy for their head and neck squamous cell carcinoma (SCC), including chemotherapy, radiation therapy, or surgery beyond biopsy
* Second primary malignancy. Exceptions are:

* Patient had a second primary malignancy but has been treated and disease free for at least 3 years
* In situ carcinoma (e.g. in situ carcinoma of the cervix)
* Non-melanomatous carcinoma of the skin
* Patients with metastatic disease beyond the neck will be excluded
* Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
* Age \< 18 years
* Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: CD4 count is \> 499/cu mm and their viral load is \< 50 copies/ml. Use of highly active antiretroviral therapy (HAART) is allowed
* Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events \[CTCAE\], version \[v.\] 5)

* Serum calcium (ionized or adjusted for albumin) \< 7 mg/dl (1.75 mmol/L) or \> 12.5 mg/dl (\> 3.1 mmol/L) despite intervention to normalize levels
* Magnesium \< 0.9 mg/dl (\< 0.4 mmol/L) or \> 3 mg/dl (\> 1.23 mmol/L) despite intervention to normalize levels
* Potassium \< 3.0 mmol/L or \> 6 mmol/L despite intervention to normalize levels
* Sodium \< 130 mmol/L or \> 155 mmol/L despite intervention to normalize levels
* Women who are pregnant, due to the teratogenic effects of radiation therapy and chemotherapy on the unborn fetus. Women of childbearing age must agree to undergo a pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* Tumor deemed unresectable with acceptable morbidity:

* Tumors \> 4 cm in size (T3 or higher)
* Tumors of the base of tongue \< 4 cm but with deep invasion of tongue musculature placing hypoglossal nerve or both lingual arteries at risk
* Significant extension into hypopharynx
* Extension into soft palate beyond 1/3 of the width
* Clinically extensive extranodal extension (ENE) e.g. radiologic evidence of invasion of carotid artery, gross extension into sternocleidomastoid muscle or deep neck muscles.

Lymph nodes larger than 6 cm without clinical ENE will be allowed
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role lead

Responsible Party

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Matin Imanguli, MD, DDS

Assistant Professor. Chief of the Division of Head and Neck Surgical Oncology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Matin Imanguli, MD, DDS

Role: PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Locations

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Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

RWJBarnabas Health - Robert Wood Johnson University Hospital, New Brunswick

New Brunswick, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey at University Hospital

Newark, New Jersey, United States

Site Status

Countries

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United States

Other Identifiers

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Pro2020002824

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2021-03006

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA072720

Identifier Type: NIH

Identifier Source: secondary_id

View Link

032008

Identifier Type: -

Identifier Source: org_study_id

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