Lower radiation therapy combined with standard chemotherapy for HPV-positive throat cancer

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

This study is testing whether using less radiation therapy along with standard chemotherapy can help people with HPV-positive throat cancer feel better while causing fewer side effects.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 121 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT05491512 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of reduced doses of radiation therapy in conjunction with standard chemotherapy for patients diagnosed with HPV-positive throat cancer. The chemotherapy regimen includes drugs such as cisplatin, carboplatin, and 5-fluorouracil, along with paclitaxel and abraxane. The goal is to determine if lower radiation doses can minimize side effects while maintaining treatment efficacy. Participants will undergo imaging studies to assess their disease status and treatment response.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of HPV-associated squamous cell carcinoma of the oropharynx and measurable disease.

Not a fit: Patients with distant metastasis or those with other types of throat cancer not associated with HPV may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to fewer side effects for patients undergoing treatment for HPV-positive throat cancer.

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
  2. Patient must have excisional biopsy or core biopsy done in order to be on protocol
* Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations.
* Oropharyngeal Carcinoma (AJCC, 7th ed.) without evidence of distant metastasis based on FDG PET/CT.
* CT 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 ≥ 50
* Age ≥ 18 Patients over 70yrs will be able to enroll in Cohort B only).
* 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/mm3
  3. Platelets ≥ 100,000 cells/mm3
  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:

  1. 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 Paclitaxel can be substituted with Abraxane (Albumin-bound 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: Exceptions can be made with PI and/or Co-Pi approval for patients to enroll on trial with a higher Bilirubin level such as Gilbert's Syndrome.

Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel).

* Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
* 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

  a. 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 Cancer Center at 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 Cancer Center at 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; Throat Cancer; Oropharyngeal Carcinoma; Oropharyngeal Cancer; Human Papilloma Virus; HPV-Positive Throat Cancer; Radiation Therapy; 22-215