A Study of Decreasing Radiation Therapy and Chemotherapy in People With Head and Neck Cancer

Official title

A Pilot Study of Radiation De-Escalation for p16 Negative Oropharyngeal Cancer and p16-Negative or Positive Laryngeal and Hypopharyngeal Cancers

Overview

The purpose of this study is to test the treatment approach of de-escalated radiation and chemotherapy followed by a planned neck dissection surgery in people with head and neck cancer. The study will look at how effective the treatment approach is against participants' cancer.

Interventions

• Diagnostic test 18F-FMISO PET/CT scan
  18F-FMISO PET/CT scan (only 1 injection) that occurs 5-10 treatment days after RT start
• Radiation Chemoradiation therapy
  * 18F-FMISO hypoxia negative patients complete CRT with 70Gy primary tumor and 50Gy de-escalated RT dose to gross nodes (if 50Gy is has pilot efficacy, then 44Gy to gross nodes; if 44Gy has pilot efficacy, then 40Gy to gross nodes). * 18F-FMISO hypoxia positive patients are taken off study and complete SOC 70Gy CRT to primary tumor and gross nodes.
• Drug Carboplatin
  The chemotherapy used in this protocol is the standard of care for head and neck cancer, cisplatin or carboplatin/5-Fluorouracil

Primary outcome measures

• Number of participants alive post-Chemo Radiation Therapy [Time frame: 2.5 years]

Eligibility criteria

Inclusion criteria

• Histologically confirmed diagnosis of SCC of the head and neck (excluding nasopharynx, nasal cavity/paranasal sinus, oral cavity, salivary, thyroid, and cutaneous primary malignancies).

• Any unknown primary SCC of the head and neck with radiographically detectable gross nodes is allowed (core or excisional biopsy acceptable; if excisional biopsy is performed, there must be residual radiographically detectable nodal disease; FNA may be acceptable only with PI and/or co-PI approval)
• If the primary site is oropharynx or unknown primary, P16 IHC must be negative.
• If the primary site is hypopharynx or larynx, any P16 status is acceptable (positive, negative, or unknown). P16 IHC is strongly encouraged when possible.
• Clinical stage T0-3 N1-2C M0 (AJCC 7th edition) without evidence of distant metastasis based on staging FDG PET/CT.
• 18 years of age or older.
• Must not have received prior radiation therapy or chemotherapy for HNC.
• Patients who have had their primary site tumor removed by surgery but still have residual grossly enlarged, radiographically detectable lymph nodes are eligible for this study.
• Karnofsky Performance Status (KPS) ≥ 70.
• CT or MRI of the Neck with and without contrast

o Note: A CT scan of the Neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools.

• Adequate hematologic function within 30 days prior to registration, defined as follows:

• White Blood Count (WBC) ≥ 2,000 cells/µL
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 8.0 g/dL; Note: The use of transfusion or other interventions to achieve Hgb ≥ 8.0 g/dL is acceptable
• Adequate renal function within 30 days prior to registration, defined as follows:

• Serum creatinine < 1.5 mg/dL or creatinine clearance (CrCl) ≥ 50 mL/min determined by 24-hour collection or estimated by Cockcroft-Gault formula: CrCl male = \[(140 - age) x (weight in kg)\] / \[(Serum Cr mg/dL) x (72)\] CrCl female = 0.85 x (CrCl male)
• Patients with serum creatinine > 1.5 mg/dL can be eligible for carboplatin-based chemotherapy with approval of co-PI (Dr. Eric Sherman
• Adequate hepatic function within 30 days prior to registration, defined as follows:

• Bilirubin < 2 mg/dL
• AST or ALT < 3 x the upper limit of normal
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential.
• The subject/legally authorized representative (LAR) must provide study-specific informed consent prior to study entry.

Exclusion criteria

• All nasopharyngeal, nasal cavity/paranasal sinus, oral cavity, salivary gland, thyroid, and cutaneous primary malignancies.
• Any T4 or N3 patients
• Any prior radiotherapy to the head and neck region.
• Any prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different non-H\&N cancer is permissible.
• Prior chemotherapy or radiotherapy within the last three years.
• Patients who underwent previous surgical resection for the same disease (except for biopsy or surgery removing primary site tumor but still present with grossly enlarged, radiographically detectable lymph nodes).
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years estimated to be ≥ 90%.
• Subjects with simultaneous primary cancers outside of the oropharynx

o Note: Exceptions can be made for patients with simultaneous primaries outside the H\&N if determined by the PI/Co-PI that the patient can proceed with protocol activities.

• Pregnant (confirmed by serum b-HCG in women of reproductive age) or breastfeeding.
• Severe, active co-morbidities 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) — Basking Ridge
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale
• Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activities) — Commack
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York

Identifiers

NCT: NCT05544136 · 22-227

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗