Comparing personalized radiation therapy to standard radiation therapy for HPV-positive throat cancer

Phase III Randomized and Double-blinded Trial of De-escalated Radiation in FMISO PET-selected Good Risk Versus Standard of Care Radiation in Unselected HPV Positive Oropharyngeal Cancer

This study is testing if a personalized radiation treatment with a lower dose can help people with HPV-positive throat cancer feel better and have fewer side effects compared to standard radiation therapy.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 291 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 9 sites (Hartford, Connecticut and 8 other locations)
• Trial ID: NCT06563479 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of a personalized approach to chemoradiation therapy, which may involve a lower dose of radiation, compared to standard chemoradiation therapy in patients with HPV-positive throat cancer. The researchers will assess whether the lower radiation dose combined with standard chemotherapy results in fewer side effects and impacts participants' quality of life. Participants will complete questionnaires to measure their quality of life throughout the study. The study includes patients with specific eligibility criteria related to HPV status and cancer staging.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with pathologically confirmed HPV-associated squamous cell carcinoma of the oropharynx and specific clinical staging.

Not a fit: Patients with HPV-negative throat cancer or those with distant metastasis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a more effective and less harmful treatment option for patients with HPV-positive throat cancer.

How similar studies have performed: Other studies have shown promise in personalized treatment approaches for cancer, suggesting potential success for this novel approach.

Eligibility criteria

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

Where this trial is running

Hartford, Connecticut and 8 other locations

• Hartford Healthcare (Data Collection Only) — Hartford, Connecticut, United States (RECRUITING)
• Baptist Alliance MCI (Data Collection Only) — Miami, Florida, United States (RECRUITING)
• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities) — Commack, New York, United States (RECRUITING)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (RECRUITING)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Nancy Lee, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Nancy Lee, MD

Conditions: HPV-Related Squamous Cell Carcinoma, oropharynx, tonsil, base of the tongue, oropharyngeal walls, radiation treatments, cisplatin, 24-200