RECRUITING

Adaptive Treatment De-escalation in Favorable Risk HPV-Positive Oropharyngeal Carcinoma

Conditions

Oropharyngeal Carcinoma HPV Positive Oropharyngeal Squamous Cell Carcinoma Radiation Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase II clinical trial. The purpose of this study is to determine the feasibility of deescalating chemoradiation treatment based on mid-treatment tumor response determined by rapid nodal shrinkage and clearance of circulating HPV plasma tumor DNA . The primary objective of this study is to evaluate progression-free survival at 2 years.

Official Title

Adaptive De-escalation of Radiation Therapy Dose in HPV-Positive Oropharyngeal Carcinoma (ART) Demonstrating Favorable Mid-Treatment Response

Quick Facts

Study Start:2017-10-18

Study Completion:2028-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03215719

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, which include the sites tonsil, base of tongue, soft palate, or posterior oropharyngeal wall. Histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma). Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. * If the primary site is biopsied, Patient's tissue must be positive for p16 by immunohistochemical staining (\>70% staining). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is not available for p16 immunohistochemistry. * Patients must have detectable HPV ctDNA Score Report at Screening or have a detectable baseline HPV ctDNA Score Report (Naveris test) if no primary site is biopsied. Must have detectable screening plasma HPV DNA (also referred to as ctHPV DNA). * Clinical stage T1-T3, N1-N2b (AJCC 7th Edition) with no distant metastases based on the following diagnostic workup: * Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration. * One of the following combinations of imaging is required within 8 weeks of registration: 1. CT scan of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast); 2. Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast) 3. Note: A CT scan of the neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging and planning tools. * Patients must provide their personal smoking history prior to registration. Patients cannot have a cumulative personal smoking history that exceeds 10 pack-years. 1. Number of pack-years = \[Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)\] / 20 2. Note: Twenty cigarettes is considered equivalent to one pack. Cigar and pipe tobacco consumption is not included in calculating lifetime pack-years. * Zubrod Performance Status of 0-1 within 8 weeks prior to registration; * Adequate hematologic function within 2 weeks prior to registration, defined as follows: * Adequate renal function within 2 weeks prior to registration, defined as follows: * Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential; * Patients who are HIV positive but who have no prior AIDS-defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B). * The patient must provide study-specific informed consent prior to study entry.	* Missing or undetectable baseline plasma HPV DNA level * Cancers considered to be from an oral cavity site (oral tongue, floor of mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive; * Carcinoma of the neck of unknown primary site origin (even if p16 positive); * Distant metastasis or adenopathy below the clavicles; * Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. * Simultaneous primary cancers or separate bilateral primary tumor sites; * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible); * Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; * Severe, active co-morbidity defined as follows: 1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; 2. Transmural myocardial infarction within the last 6 months; 3. Acute bacterial or fungal infection intravenous antibiotics at the time of registration; 4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration; 5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those listed in 4.1.10. 6. Acquired immune deficiency syndrome (AIDS) based upon the current CDC definition with immune compromise greater than that noted in section 4.1.12; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immune-compromised patients. * Pregnancy; this exclusion is necessary because the treatment in this study may be significantly teratogenic * Prior allergic reaction to cisplatin. * Exclusion Criteria for MRI: Normal MRI exclusion criteria will apply, including those on the following list. A standard MRI safety form will be used to identify potential conditions warranting exclusion. * Electrical implants such as cardiac pacemakers or perfusion pumps * Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial heart, valves with steel parts, metal fragments, shrapnel, bullets, tattoos near the eye, or steel implants * Ferromagnetic objects such as jewelry or metal clips in clothing * Claustrophobia * History of seizures * Patients with GFR \< 15 ml/min/1.73m2 or who are on dialysis will not have DCE-MRI scan. These patients will have conventional anatomical MRI without contrast.

Inclusion Criteria

Exclusion Criteria

* Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, which include the sites tonsil, base of tongue, soft palate, or posterior oropharyngeal wall. Histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma). Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx.
* If the primary site is biopsied, Patient's tissue must be positive for p16 by immunohistochemical staining (\>70% staining). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is not available for p16 immunohistochemistry.
* Patients must have detectable HPV ctDNA Score Report at Screening or have a detectable baseline HPV ctDNA Score Report (Naveris test) if no primary site is biopsied. Must have detectable screening plasma HPV DNA (also referred to as ctHPV DNA).
* Clinical stage T1-T3, N1-N2b (AJCC 7th Edition) with no distant metastases based on the following diagnostic workup:
* Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration.
* One of the following combinations of imaging is required within 8 weeks of registration:
1. CT scan of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast);
2. Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast)
3. Note: A CT scan of the neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging and planning tools.
* Patients must provide their personal smoking history prior to registration. Patients cannot have a cumulative personal smoking history that exceeds 10 pack-years.
1. Number of pack-years = \[Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)\] / 20
2. Note: Twenty cigarettes is considered equivalent to one pack. Cigar and pipe tobacco consumption is not included in calculating lifetime pack-years.
* Zubrod Performance Status of 0-1 within 8 weeks prior to registration;
* Adequate hematologic function within 2 weeks prior to registration, defined as follows:
* Adequate renal function within 2 weeks prior to registration, defined as follows:
* Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential;
* Patients who are HIV positive but who have no prior AIDS-defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
* The patient must provide study-specific informed consent prior to study entry.

* Missing or undetectable baseline plasma HPV DNA level
* Cancers considered to be from an oral cavity site (oral tongue, floor of mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive;
* Carcinoma of the neck of unknown primary site origin (even if p16 positive);
* Distant metastasis or adenopathy below the clavicles;
* Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease.
* Simultaneous primary cancers or separate bilateral primary tumor sites;
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
* Severe, active co-morbidity defined as follows:
1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
2. Transmural myocardial infarction within the last 6 months;
3. Acute bacterial or fungal infection intravenous antibiotics at the time of registration;
4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those listed in 4.1.10.
6. Acquired immune deficiency syndrome (AIDS) based upon the current CDC definition with immune compromise greater than that noted in section 4.1.12; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immune-compromised patients.
* Pregnancy; this exclusion is necessary because the treatment in this study may be significantly teratogenic
* Prior allergic reaction to cisplatin.
* Exclusion Criteria for MRI: Normal MRI exclusion criteria will apply, including those on the following list. A standard MRI safety form will be used to identify potential conditions warranting exclusion.
* Electrical implants such as cardiac pacemakers or perfusion pumps
* Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial heart, valves with steel parts, metal fragments, shrapnel, bullets, tattoos near the eye, or steel implants
* Ferromagnetic objects such as jewelry or metal clips in clothing
* Claustrophobia
* History of seizures
* Patients with GFR \< 15 ml/min/1.73m2 or who are on dialysis will not have DCE-MRI scan. These patients will have conventional anatomical MRI without contrast.

Contacts and Locations

Study Contact

Kenneth Hu

CONTACT

212-731-5003

Kenneth.Hu@nyulangone.org

Fraustina Hsu

CONTACT

cancertrials@nyulangone.org

Principal Investigator

Kenneth Hu, MD

PRINCIPAL_INVESTIGATOR

NYU Langone Health

Study Locations (Sites)

New York University School of Medicine

New York, New York, 10016

United States

Collaborators and Investigators

Sponsor: NYU Langone Health

Kenneth Hu, MD, PRINCIPAL_INVESTIGATOR, NYU Langone Health

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-10-18

Study Completion Date2028-12

Study Record Updates

Study Start Date2017-10-18

Study Completion Date2028-12

Terms related to this study

Keywords Provided by Researchers

Radiation Therapy

Additional Relevant MeSH Terms

Oropharyngeal Carcinoma
HPV Positive Oropharyngeal Squamous Cell Carcinoma