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

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ClinicalTrials.gov Identifier: NCT04920344
Recruitment Status : Not yet recruiting
First Posted : June 9, 2021
Last Update Posted : June 22, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Matin Imanguli, MD, DDS, Rutgers, The State University of New Jersey

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Procedure: Transoral Surgery Radiation: External Beam Radiation Therapy Drug: Cisplatin Procedure: Incisional Tumor Biopsy Other: Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment Other: MD Anderson Dysphagia Index Other: University of Washington Quality of Life Questionnaire Other: Euro-QOL 5 dimension scale questionnaire Diagnostic Test: Modified barium swallow (MBS) evaluation with aspiration-penetration scale Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Swallowing Outcomes and Circulating Tumor DNA in Patients With HPV Related Oropharyngeal Cancer Treated With Transoral Surgery and Reduced Intensity Adjuvant Therapy
Estimated Study Start Date : July 2021
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022

Arm Intervention/treatment
Active Comparator: 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.
Procedure: Transoral Surgery
Patients will undergo transoral surgery
Other Name: Therapeutic Conventional Surgery

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

Other: 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.
Other Name: Circulating ctDNA levels assessment

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.
Other Name: MDADI

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.
Other Name: UW QOL questionnaire

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.
Other Name: EQ-5D-5L

Diagnostic Test: 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.

Other Name: MBS with PEN/ASP scale

Experimental: 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.
Procedure: Transoral Surgery
Patients will undergo transoral surgery
Other Name: Therapeutic Conventional Surgery

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

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

Other: 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.
Other Name: Circulating ctDNA levels assessment

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.
Other Name: MDADI

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.
Other Name: UW QOL questionnaire

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.
Other Name: EQ-5D-5L

Diagnostic Test: 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.

Other Name: MBS with PEN/ASP scale

Experimental: 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.
Procedure: Transoral Surgery
Patients will undergo transoral surgery
Other Name: Therapeutic Conventional Surgery

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

Drug: Cisplatin
Patients in Group III will receive cisplatin, 30 mg/m2, administered intravenously weekly per for 6 weeks.
Other Name: Cisplatin Chemotherapy

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

Other: 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.
Other Name: Circulating ctDNA levels assessment

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.
Other Name: MDADI

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.
Other Name: UW QOL questionnaire

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.
Other Name: EQ-5D-5L

Diagnostic Test: 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.

Other Name: MBS with PEN/ASP scale




Primary Outcome Measures :
  1. MD Anderson Dysphagia Index (MDADI) [ Time Frame: At baseline. ]
    MDADI is a 20 item quality of life instrument specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients and has been widely used and validated in this population. The total score ranges from 20 to 100 with the higher score indicating higher level of function.

  2. MD Anderson Dysphagia Index (MDADI) [ Time Frame: At 24 weeks post completion of therapy. ]
    MDADI is a 20 item quality of life instrument specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients and has been widely used and validated in this population. The total score ranges from 20 to 100 with the higher score indicating higher level of function.

  3. MD Anderson Dysphagia Index (MDADI) [ Time Frame: At 1 year post completion of therapy. ]
    MDADI is a 20 item quality of life instrument specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients and has been widely used and validated in this population. The total score ranges from 20 to 100 with the higher score indicating higher level of function.


Secondary Outcome Measures :
  1. Locoregional control. [ Time Frame: At 3 years post completion of therapy ]
    Will be assessed using survival analysis (e.g., Kaplan-Meier method and Cox proportional hazards model).

  2. Disease free survival. [ Time Frame: At 3 years post completion of therapy ]
    Will be assessed using survival analysis (e.g., Kaplan-Meier method and Cox proportional hazards model).

  3. Progression free survival. [ Time Frame: At 3 years post completion of therapy ]
    Will be assessed using survival analysis (e.g., Kaplan-Meier method and Cox proportional hazards model).

  4. Overall survival. [ Time Frame: At 3 years post completion of therapy ]
    Will be assessed using survival analysis (e.g., Kaplan-Meier method and Cox proportional hazards model).

  5. University of Washington Quality of Life Questionnaire [ Time Frame: At baseline, 24 weeks and 1 year post completion of therapy ]
    University of Washington Questionnaire is a 15 item quality of life instrument specifically designed for head and neck cancer patients. Scoring is scaled to so that a score of 0 represents the worst possible response, and a score of 100 represents the best possible response. The higher the score - the better the outcome.

  6. European Quality of Life Five Dimension Five Level Scale Questionnaire scores [ Time Frame: At baseline, 24 weeks, and 1 year post completion of therapy ]

    Euro-QOL 5 dimension scale is a generic quality of life and cost utility instrument widely used and validated for multiple disease settings, including head and neck cancer.

    Euro-QOL 5 dimension scale is a preference-based HRQL measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers can be converted into EQ-5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).


  7. Rate of gastrostomy tube dependence [ Time Frame: At baseline, 24 weeks, and 1 year post completion of therapy ]
    Percentage of patients requiring a gastrostomy tube after completion of therapy will be analyzed using generalized linear model (GLM) analysis.

  8. Penetration-Aspiration Score on Modified Barium Swallow examination [ Time Frame: Baseline and 1 year post completion of therapy ]

    Objective swallowing function assessment using modified barium swallow (MBS) evaluation with aspiration-penetration scale.

    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. The higher the score, the worse is the outcome.


  9. Correlation of circulating tumor deoxyribonucleic acid (ctDNA) levels with known adverse pathological features [ Time Frame: At baseline and at 4 weeks post-surgery ]
    Correlation of ctDNA levels at baseline with known adverse pathological features such as, number of involved lymph nodes, extranodal extension and positive margins. Will be analyzed using GLM analysis.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04920344


Locations
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United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
Contact: Matin Imanguli, MD, DDS    732-235-6333    mi256@rwjms.rutgers.edu   
Principal Investigator: Matin Imanguli, MD, DDS         
RWJBarnabas Health - Robert Wood Johnson University Hospital, New Brunswick
New Brunswick, New Jersey, United States, 08903
Contact: Matin Imanguli, MD, DDS    732-235-6333    mi256@rwjms.rutgers.edu   
Principal Investigator: Matin Imanguli, MD, DDS         
Rutgers Cancer Institute of New Jersey at University Hospital
Newark, New Jersey, United States, 07103
Contact: Dylan Roden, MD, MPH    973-972-5053    dr906@njms.rutgers.edu   
Sub-Investigator: Dylan Roden, MD, MPH         
Sponsors and Collaborators
Rutgers, The State University of New Jersey
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Matin Imanguli, MD, DDS Rutgers Cancer Institute of New Jersey
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Responsible Party: Matin Imanguli, MD, DDS, Assistant Professor. Chief of the Division of Head and Neck Surgical Oncology, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT04920344    
Other Study ID Numbers: Pro2020002824
032008 ( Other Identifier: Rutgers Cancer Institute of New Jersey )
NCI-2021-03006 ( Registry Identifier: NCI CTRP registry )
P30CA072720 ( U.S. NIH Grant/Contract )
First Posted: June 9, 2021    Key Record Dates
Last Update Posted: June 22, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Antineoplastic Agents