Recruiting
Phase 3

Personalized Radiation Therapy

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT06563479

Conditions

HPV-Related Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

FMISO-PET Scan

Chemoradiation

Chemoradiation

Assessments

Study Details

Brief summary:

The researchers are doing this study to find out if a personalized approach to chemoradiation therapy (which may include a lower dose of radiation) is as effective as the standard chemoradiation therapy in people with HPV-positive throat cancer. Other purposes of this study include looking at the following:

  • Whether a lower dose of radiation in combination with standard chemotherapy causes fewer side effects than the standard dose of radiation therapy in combination with standard chemotherapy
  • How the study approaches (lower dose of radiation therapy + standard chemotherapy and standard dose of radiation therapy + standard chemotherapy) affect participants' quality of life. The researchers will measure quality of life by having participants fill out questionnaires.

Conditions

HPV-Related Squamous Cell Carcinoma

Study ID

NCT06563479

Start date

Aug 19, 2024

Status verified date

Jul, 2026

Completion date

Aug, 2027

Anticipated

Primary completion date

Aug, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) or squamous cell carcinoma with an unknown primary. Surgical removal of primary site is allowed.
  • Patients must test positive for both p16 expression (70% nuclear and cytoplasm expression; Ventana Medical Systems) and mRNA HPV in situ hybridization (RNAscope® 2.5 HD Reagent kit (Advanced Cell Diagnostics, Inc, Hayward, CA). Any CLIA certified testing method can be used.
  • Clinical stage Tx-2, N1-2c (AJCC, 7th ed.) without evidence of distant metastasis based on FDG PET/CT.
  • ECOG Performance Status of 0-1 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) ≥ 1,500 cells/mm\^3
  • Platelets ≥ 100,000 cells/mm\^3
  • Hemoglobin ≥ 10.0 g/dl
  • Adequate renal function within 30 days prior to registration, defined as follows:

o Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = \[(140 - age) x (wt in kg)\] \[(Serum Cr mg/dl) x (72)\] CCr female = 0.85 x (CrCl male)
  • Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
  • The patient must provide study-specific informed consent prior to study entry
  • Optional section of the protocol: Patients must be able to undergo MRI scans, i.e. not claustrophobic

Exclusion Criteria:

  • Patients with prior head and neck radiation therapy where there is >30% overlap with the current head and neck radiation fields. Exceptions can be made if determined by the PI/Co-PI that the patient can proceed with protocol activities
  • Patients whose tumors are borderline T4 based on anterior tumor extension to the extrinsic muscles of the tongue
  • Patients with simultaneous primary cancers outside of the oropharynx

o 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

o Note: Exceptions can be made for patients with prior malignancies outside the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • No particle therapy
  • Patients who are deemed non-compliant to all the protocol related activities
  • Contraindications to receive either cisplatin or the combination of carboplatin/5-fluorouracil at the prescribed doses.
  • 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 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

Study Design

Enrollment

291 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Personalized Chemoradiation Therapy

Patient without evidence of hypoxia will receive 30Gy in 2Gy per fraction. Concurrent chemotherapy will be given as per guidelines. After completion of chemotherapy and radiation therapy, a 4 month (+/- 4 weeks) posttreatment standard FDG PET/CT scan will be performed and if there is persistent disease, standard neck dissection will be performed. Further standard of care will be given pending pathologic findings.1. Hypoxia negative: The entire target volume which includes GTV and CTV will receive 30Gy in 2 Gy per fraction over 15 days (PTV30). 2. Hypoxia positive (same as the standard of care): The CTV will receive 50Gy in 2Gy per fraction over 25 days. This is name PTV50 and will receive 50Gy in 2Gy per fraction over 25 days. The GTV will receive an additional boost of 20Gy in 2 Gy per fraction so that the total PTV70 dose is 70Gy.

active comparator: Standard Chemoradiation Therapy

Patient will receive 70Gy in 2Gy per fraction regardless of hypoxia status. Concurrent chemotherapy will be given as per guidelines. After completion of chemotherapy and radiation therapy, a 4 month (+/- 4 weeks) posttreatment standard FDG PET/CT scan will be performed and if there is persistent disease, standard neck dissection will be performed. Further standard of care will be given pending pathologic findings.

Interventions

FMISO-PET Scan

Patients will undergo 18F-FMISO scan (only 1 injection) that occurs at week two of radiation treatment, typically day 10 but a window of 8-10 radiation treatment days\* after start of radiation is allowed.

Chemoradiation

30 Gy or 70 Gy of radiation in combination with standard chemotherapy (cisplatin, carboplatin, and 5-FU)

Chemoradiation

70 Gy of radiation in combination with standard chemotherapy (cisplatin, carboplatin, and 5-FU)

Assessments

EQ-5D-5L (5 questions); 2. MDADI-HN (total of 20 questions); 3. COST-FACIT (total of 12 questions).

Primary outcome measure

  • overall survival [ Time Frame: 2 years ]

Central Contacts and Locations

Central contacts

Nancy Lee, MD

212-639-3341leen2@mskcc.org

Nadeem Riaz, MD

646-888-3495

Locations

Hartford Healthcare (Data Collection Only)

Recruiting

Hartford, Connecticut, United States, 06102

Contacts

Charles Rutter, MD

860-972-2803

Baptist Alliance MCI (Data Collection Only)

Recruiting

Miami, Florida, United States, 33143

Contacts

Noah Kalman, MD

786-596-2000

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Nancy Lee, MD

212-639-3341

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Nancy Lee, MD

212-639-3341

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Nancy Lee, MD

212-639-3341

Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities)

Recruiting

Commack, New York, United States, 11725

Contacts

Nancy Lee, MD

212-639-3341

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Recruiting

Harrison, New York, United States, 10604

Contacts

Nancy Lee, MD

212-639-3341

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

Recruiting

New York, New York, United States, 10065

Contacts

Nancy Lee, MD

212-639-3341

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Recruiting

Uniondale, New York, United States, 11553

Contacts

Nancy Lee, MD

212-639-3341

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Jul 28, 2026

Last verified

Jul, 2026

Keywords

  • oropharynx
  • tonsil
  • base of the tongue
  • oropharyngeal walls
  • radiation treatments
  • cisplatin
  • 24-200

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-07-28.