Lower radiation therapy with chemotherapy for HPV-positive throat cancer

Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Advanced Stage Human Papilloma Virus Associated Oropharyngeal Carcinoma

This study is testing if giving lower doses of radiation along with chemotherapy can effectively treat patients with HPV-positive throat cancer just as well as the usual higher doses of radiation.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT06984861 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of reduced doses of radiation therapy combined with standard chemotherapy for patients with HPV-positive oropharyngeal carcinoma. The treatment regimen includes chemotherapy drugs such as cisplatin, carboplatin, and 5-fluorouracil (5-FU), administered alongside a lower radiation dose over a shorter treatment period. Researchers will assess whether this approach is as effective as the standard treatment protocol, which involves higher radiation doses. The study will also utilize 18F-FMISO PET/CT scans and questionnaires to gather data on treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are individuals with pathologically confirmed HPV-positive squamous cell carcinoma of the oropharynx who have measurable disease.

Not a fit: Patients with HPV-negative throat cancer or those without measurable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to less radiation exposure for patients while maintaining effective cancer treatment.

How similar studies have performed: Other studies have shown promise in reducing radiation doses for similar conditions, suggesting potential for success in this 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) from biopsy, surgical resection or excisional biopsy regardless of margin status.

  1. 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:

  1. White Blood Count (WBC) ≥ 2 K/mcL
  2. Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
  3. Platelets ≥ 100,000 cells/mm\^3
  4. 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:

  a. 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) Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel
* Adequate hepatic function within 30 days prior to registration, defined as follows:

  1. Bilirubin ≤ 2 mg/dl
  2. AST or ALT ≤ 3 x the upper limit of normal Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel. Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
* One cycle of induction chemo therapy is allowed prior to registration based on clinical needs.
* The subject must provide study-specific informed consent prior to study entry Subject able to undergo MRI scans except for major medical contraindications like presence of a pacemaker or approved by the PI or the CO-PI that the subject does not need to undergo MRI scans

Exclusion Criteria:

* 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)

  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 requiring 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

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• 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: Oropharyngeal Carcinoma, Human Papilloma Virus Associated, Chemoradiation, T3-4/N0-2c or any N3, 25-040