A Study of Reduced Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer

NCT06984861 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-040
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 7

Brief Summary

The researchers are doing this study is to find out if lower doses (given in fewer treatments over a shorter period of time) of radiation therapy in combination with standard-of-care chemotherapy is an effective treatment for people with Human Papilloma Virus (HPV)-positive throat cancer and works as well as the standard doses of radiation therapy in combination with standard-of-care chemotherapy. The chemotherapy drugs used in combination with radiation therapy in this study include cisplatin, carboplatin, and 5-fluorouracil (5-FU).

Conditions

Oropharyngeal Carcinoma

Keywords

Human Papilloma Virus Associated; Chemoradiation; T3-4/N0-2c or any N3; 25-040

Outcome Measures

Primary Outcomes (1)

• Locoregional control

  Researchers will test the null hypothesis H0: P=78% vs the alternative hypothesis H1:P=91%, where P represents the 2-year locoregional control (LRC). We will use the Kaplan-Meier method to estimate the LRC rate at 2 years and construct a 0.975 1-sided confidence interval in order to achieve a test size alpha = 0.05 (this is based on a finite-sample correction using 100,000 simulations).

  2 years

Study Arms (1)

Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer

EXPERIMENTAL

Subjects will first undergo 6 weeks of standard induction chemotherapy and if downstaged to T1-2 and \<N3 and also have no evidence of hypoxia will undergo a major de-escalated radiation therapy to 30Gy concurrent with standard chemotherapy. Hypoxia status is determined by the absence of hypoxia uptake on Fluorine-18-Labeled Fluoro-Misonidazole (18F-FMISO) PET/CT imaging (8-10 treatment days after start of chemoradiation), which has an FDA approved IND for use in humans . If the 18F-FMISO PET is negative for hypoxia, the patient will receive 30Gy concurrent with 2 cycles of chemotherapy. If the 18F-FMISO PET is positive for hypoxia, the patient will receive standard of care 70Gy concurrent with 3 cycles of chemotherapy. An optional 18F-FMISO scan will also be offered at baseline.

Diagnostic Test: 18F-FMISO PET/CT Scan; Combination Product: Chemoradiation; Other: Questionnaires

Interventions

18F-FMISO PET/CT Scan DIAGNOSTIC_TEST

The 18F-FMISO PET/CT Scan Protocol consists first of an IV bolus injection of approximately 5-10 mCi of the radiotracer. Subjects will undergo 18F-FMISO scan (only 1 injection) occurs at 8-10 treatment days\* into chemoradiation. Each patient will have a baseline staging FDG PET scan which is used to localize the tumor at the primary site and all suspicious cervical neck nodes (\> 1 cm in short axis diameter with focal abnormal increased FDG avidity). These lesions are then assessed on the respective 18F-FMISO PET/CT.

Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer

Chemoradiation COMBINATION_PRODUCT

Patients will start with induction chemotherapy of carboplatin, paclitaxel and cetuximab for 6 weeks and when downstaged to T1-2 and \< N3, the patient is eligible to receive concurrent chemoradiation per protocol. All subjects will undergo radiation treatments (IMRT and/or proton therapy). A total radiation therapy of 30Gy will be delivered to the oropharynx and neck at 2Gy per fraction per day over 15 days for patients who exhibited no evidence of hypoxia on the intra-treatment 18F-FMISO PET/CT. Concurrent chemotherapy (2 cycles) will be given. After completion of chemotherapy and radiation therapy, a 4 month (+/-4 weeks)

Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer

Questionnaires OTHER

EQ-5D-5L, MDADI-HN, COST-FACIT

Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer

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 HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from biopsy, surgical resection or excisional biopsy regardless of margin status.
• Squamous cell carcinoma of the neck of unknown primary is allowed with excision biopsy of a lymph node (or core biopsy) or consent from the PI or co-PI. Patient must have excisional biopsy or core biopsy done in order to be on protocol.
• Note: Evidence of HPV associated oropharyngeal cancer from either the primary tumor site or from a lymph node. A patient is HPV positive when he or she tests positive having tested positive for both p16 expression (70% nuclear and cytoplasm expression; Ventana Medical Systems) and mRNA HPV in situ hybridization.
• Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations.
• T3-4/N0-2c or any N3 regardless of Tstage (AJCC 7th Edition) HPV+ OPC\* or HPV associated squamous cell carcinoma with nodal metastasis (es) but unknown primary sites without evidence of distant metastasis based on FDG PET/CT.
• CT Neck with contrast or MRI of the neck with and without contrast Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools.
• ECOG Performance Status of 0-2 or KPS ≥ 70
• Age ≥ 18
• Adequate hematologic function within 30 days prior to registration, defined as follows:
• White Blood Count (WBC) ≥ 2 K/mcL
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
• Platelets ≥ 100,000 cells/mm\^3
• 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 30 days prior to registration, defined as follows:

You may not qualify if:

• Subjects with prior head and neck radiation therapy
• Subjects with simultaneous primary cancers outside of the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
• Note: Exceptions can be made for patients with simultaneous primaries outside the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years to be 90% or greater
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
• Severe, active co-morbidity defined as follows (exceptions can be made if approved by the PI and/or co-PI)
• 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 requiring 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Chemoradiotherapy; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Nancy Lee, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nancy Lee, MD

CONTACT

212-639-3341; leen2@mskcc.org

Nadeem Riaz, MD

CONTACT

646-888-3495

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This non-randomized phase II study.

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 22, 2025
• Study Start: May 13, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)