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

NCT03215719 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 17-00330
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oropharyngeal Carcinoma; HPV Positive Oropharyngeal Squamous Cell Carcinoma

Keywords

Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 2 years

  The non-inferiority (NI) analysis will be conducted on the pooled de-escalated cohort (Arms 3+4 combined) to evaluate whether the 2-year PFS is acceptable relative to the historical benchmark. For Arm 3 and Arm 4 separately, Kaplan-Meier curves and 2-year PFS estimates with 95% confidence intervals will be provided. Patients who do not experience progression of disease and have not died will be censored on the date of last follow up.

  2 Years

Study Arms (4)

Arm 1: Dose de-escalation (6 weeks)

EXPERIMENTAL

26 participants demonstrating a favorable response defined as \>40% nodal shrinkage were eligible to receive the de-escalated treatment regimen (6 doses of weekly cisplatinum with 6 weeks of radiation to a total dose of 60Gy). This arm is closed and has been replaced with Arm 3.

Radiation: Dose-Deescalated Treatment; Drug: Cisplatinum

Arm 2: Standard radiation therapy + cisplatinum (7 weeks)

ACTIVE COMPARATOR

Participants will receive standard radiation therapy and cisplatinum for 7 weeks.

Radiation: Standard Radiation Treatment; Radiation: Dose-Deescalated Treatment; Drug: Cisplatinum

Arm 3: Dose de-escalation (6 weeks)

EXPERIMENTAL

For participants who achieve (a) rapid nodal shrinkage on interval CT scan but slow / unknown ctHPV DNA clearance OR (b) slow nodal shrinkage on interval CT scan but rapid ctHPV DNA clearance at week 4, radiation treatment will be de-escalated to a total dose of 60Gy/6 weeks with 6 doses of weekly (cisplatinum). This arm replaced Arm 1.

Radiation: Dose-Deescalated Treatment; Drug: Cisplatinum

Arm 4: Dose de-escalation (5 weeks)

EXPERIMENTAL

For participants who achieve both a favorable nodal response (\>40%) on interval CT scan as well as rapid ctHPV DNA clearance at week 4, radiation treatment will be further de-escalated to a total dose of 50 Gy/5 weeks with 5 doses of weekly cisplatinum).

Radiation: Dose-Deescalated Treatment; Drug: Cisplatinum

Interventions

Standard Radiation Treatment RADIATION

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.

Arm 2: Standard radiation therapy + cisplatinum (7 weeks)

Dose-Deescalated Treatment RADIATION

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

Also known as: Intensity Modulated Radiation Therapy (IMRT)

Arm 1: Dose de-escalation (6 weeks); Arm 2: Standard radiation therapy + cisplatinum (7 weeks); Arm 3: Dose de-escalation (6 weeks); Arm 4: Dose de-escalation (5 weeks)

Cisplatinum DRUG

Standard of care chemotherapy

Arm 1: Dose de-escalation (6 weeks); Arm 2: Standard radiation therapy + cisplatinum (7 weeks); Arm 3: Dose de-escalation (6 weeks); Arm 4: Dose de-escalation (5 weeks)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• CT scan of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast);
• Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast)
• 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.
• Number of pack-years = \[Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)\] / 20
• 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.

You may not qualify if:

• 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:
• 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 intravenous antibiotics at the time of registration;
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
• 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.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

RECRUITING

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; Cisplatin

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Kenneth Hu, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kenneth Hu

CONTACT

212-731-5003; Kenneth.Hu@nyulangone.org

Fraustina Hsu

CONTACT

cancertrials@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 12, 2017
• Study Start: October 18, 2017
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

US (1)