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

June 12, 2023 updated by: NYU Langone Health
This will be a phase II single-arm 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.

Study Overview

Detailed Description

The secondary objectives will include 2-year loco-regional control and overall survival, quality of life, and late toxicity. Quality of life outcomes will be assessed with a validated, self-reported questionnaire. Late toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events. Additionally, the prognostic value of positive HPV in salivary rinse as well as plasma at mid and post- treatment time points will be evaluated with a baseline evaluation pre-treatment. Radiomic analysis of pre-treatment imaging will be correlated with outcomes.

Study Type

Interventional

Enrollment (Estimated)

144

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • New York University School of Medicine
        • Contact:
        • Principal Investigator:
          • Kenneth Hu, MD

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion 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.
  • 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 available for p16 immunohistochemistry.
  • Patients must have detectable circulating plasma HPV DNA at baseline
  • Clinical stage T1-T2, N1-N2b or 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. Or a 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:

Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl; Note: the use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.

  • Adequate renal function within 2 weeks prior to registration, defined as follows:

    a.Serum creatinine ≤ mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24 hour collection or estimated by Cockcorft-Gault formula: i.CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] ii.CCr female = 0.85 x (CrCl male)

  • 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.

Exclusion Criteria:

  • 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 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
  • Diabetes a.In addition, 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 and DW-MRI,

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HPV-Positive Oropharyngeal Carcinoma (OPSCC)
Standard radiation therapy + cisplatinum
Intensity-modulated radiation therapy (IMRT) is an advanced type of radiation therapy used to treat cancer and noncancerous tumors. IMRT uses advanced technology to manipulate photon and proton beams of radiation to conform to the shape of a tumor. Patients will be treated with intensity-modulated radiation therapy (IMRT) with megavoltage photons
Other Names:
  • Intensity Modulated Radiation Therapy (IMRT)
Standard of care chemotherapy
An interval scan at 4 weeks to assess for a good response defined as >40% nodal shrinkage will stratify patients into receiving standard treatment (≤40% nodal shrinkage) or a dose-deescalated treatment regimen (>40% nodal shrinkage). Those with nodal shrinkage and clearance of circulating plasma HPV DNA shall undergo further treatment de-escalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival at 2 years
Time Frame: 2 Years
The rate of progression-free survival will be estimated using time to failure methods; Kaplan Meier curves will be provided and the rate at 2 years will be estimated using a 95% confidence interval. Patients who do not experience progression of disease and have not died will be censored on the date of last follow up.
2 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kenneth Hu, MD, 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 Major Dates

Study Start (Actual)

July 10, 2017

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

July 11, 2017

First Submitted That Met QC Criteria

July 11, 2017

First Posted (Actual)

July 12, 2017

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

June 12, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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