Protocol Summary

Protocol No.: OCR15979

Sponsor Protocol No.: NRG-HN003

Study Title
A Phase I and Expansion Cohort Study of Adjuvant Cisplatin, Intensity-Modulated Radiotherapy, and MK-3475 (Pembrolizumab) in High-risk Head and Neck Squamous Cell Carcinoma (HNSCC)

Principal Investigator(s)
Silver, Natalie

Objective
This phase I trial studies the side effects and best dose of pembrolizumab when given together with cisplatin and intensity-modulated radiation therapy, in treating patients with stage III-IV squamous cell carcinoma of the head and neck. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Intensity-modulated radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab with cisplatin and intensity-modulated radiation therapy may work better in treating patients with squamous cell carcinoma of the head and neck.

Description
Patients receive cisplatin intravenously (IV) over 1-2 hours once weekly for weeks 1-6 and pembrolizumab IV over 30 minutes every 3 weeks in weeks 9, 12, 15, 18, and 21. Patients also undergo intensity-modulated radiation therapy (IMRT) in weeks 1-6. Patients may also receive pembrolizumab IV over 30 minutes in weeks 3, 6, 24, and 27. After completion of study treatment, patients are followed up at months 6, 9, 12, 15, 18, 21, 24, 30, and 36.

Phase: Phase I

Age Group: Adult

Scope: National

Treatment
Treatment (cisplatin, pembrolizumab, IMRT):
Patients receive cisplatin IV over 1-2 hours once weekly for weeks 1-6 and pembrolizumab IV over 30 minutes every 3 weeks in weeks 9, 12, 15, 18, and 21. Patients also undergo IMRT in weeks 1-6. Patients may also receive pembrolizumab IV over 30 minutes in weeks 3, 6, 24, and 27.

Detailed Eligibility
Inclusion Criteria:
1. Ages 18 years old and older
2. Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), hypopharynx or larynx
3. Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx squamous cell carcinoma (SCC) within 63 days prior to registration; note: patients may have a biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but demonstrate rapid gross recurrence or are determined to have gross persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
4. Patients must have at least one of the following high risk pathologic features:
- Extracapsular nodal extension
- Invasive cancer at the primary tumor resection margin (tumor on ink); Note: Patients who have a positive margin and undergo re-resection with final negative margin are eligible only if they can be enrolled within 63 days of initial gross total resection AND extracapsular nodal extension was also present; patients who have a positive margin and undergo re-resection with final negative margin and do not have extracapsular nodal extension, are NOT eligible
5. Pathologic stage III or IV HNSCC, including no distant metastases, based on the following minimum diagnostic workup:
- General history/physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration
- Examination by an ear nose and throat (ENT) or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation
- Pre-op Imaging of the head and neck: a neck computerized tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via transfer of images and data (TRIAD); the report is to be uploaded into Rave
- Chest imaging with either a CT scan (with or without contrast) or CT/PET (with or without contrast) that includes the chest within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
6. For patients with oropharyngeal cancer only: the institution will do p16 testing, and if p16 is negative, this tissue must be submitted for central review for confirmation before Step 2 registration; note: if the institution finds that the patient is p16 positive, the patient is excluded from this trial on the basis of distinct biology, prognosis, and low- or intermediate-risk rather than high-risk status
7. Zubrod performance status of 0-1 within 28 days prior to registration
8. Absolute neutrophil count (ANC): >= 1,500 /mm^3
9. Platelets: >= 100,000 / mm^3
10. Hemoglobin: >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)

** Contact study team for complete eligibility details.

Applicable Disease Sites
Head & Neck Cancer

Participating Institutions
UF Gainesville : Allison Trainor

Contact
Allison Trainor
Phone: +1 352-265-0680 ext. 50703

Email: awickham@ufl.edu