NCT03323463

Major De-escalation to 30 Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma

A Prospective Single Arm Non-inferiority Trial of Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Human Papilloma Virus Associated Oropharyngeal Carcinoma (Major De-escalation to 30Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 316 (estimated)
• Sponsor: Memorial Sloan Kettering Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to demonstrate that participants with HPV positive and hypoxia negative T1-2, N1-2c (AJCC, 7th ed.) oropharyngeal squamous cell carcinoma receiving a major de-escalated radiation therapy with 2 cycles of standard chemotherapy is not inferior to comparable subjects treated with the current standard chemoradiation. Accrual for Cohort A has been completed. Cohort B is active and continues to enroll participants where surgery is optional and proton is allowed.

Detailed description

This non-randomized non-inferiority study will enroll HPV associated oropharyngeal carcinoma subjects. Subjects who also have no evidence of hypoxia will undergo a major de-escalated radiation therapy concurrent with standard chemotherapy. Hypoxia status will be determined by 1 BF-FMISO PET /CT imaging. If this baseline scan shows no evidence of hypoxia, the subject will receive 30Gy concurrent with 2 cycles of chemotherapy. If this baseline scan shows evidence of hypoxia, a repeat 1 BF-FMISO scan will be done 5-10 treatment days after start of radiation therapy. If the repeat 1 BF-FMISO scan PET /CT demonstrates no evidence of hypoxia, the subject will receive 30Gy concurrent with 2 cycles of chemotherapy. If the repeat 1 BF-FMISO scan PET /CT demonstrates hypoxia, the subject will receive 70Gy concurrent with 2 cycles of chemotherapy. At 4 (+/- 4 weeks) months after chemoradiation, a neck dissection will be done unless the subjects FDG PET /CT scan at that time shows no evidence of disease of which the subject can be observed as per current standard of care.

Conditions

• HPV-Associated Oropharyngeal Squamous Cell Carcinoma
• Squamous Cell Carcinoma of the Neck

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	F-FMISO PET/CT Scan	All subjects on Cohort A and the first 100 subjects accrued to Cohort B will undergo a pre-treatment F-FMISO scan PET/CT scan pretreatment. For both Cohort A and Cohort B, FMISO scan will be repeated between the 5th-10th RT day if pre-treatment scan is hypoxic. If the repeat 18F-FMISOscan PET/CT demonstrates hypoxia, the subject will receive 70Gy concurrent with 2 cycles of chemotherapy. All subjects accrued onto Cohort B after 100 accruals will undergo only one 18F-FMISO scan done 5-10 treatment days after start of radiation therapy.
RADIATION	30 Gy over 3 weeks	Treatment will be delivered as one fraction per day on a standard 5 day per week schedule (excluding weekends and holidays), total of 30 Gy over 3 weeks at 2 Gy per fraction each day. The gross nodes, the primary/postoperative bed if applicable, all subclinical areas at risk for disease will receive the same dose at 30Gy.
DRUG	Cisplatin	Cycle 1 (week 1): At the start of week 1 of IMRT, subjects will receive cisplatin 100 mg/m2 intravenously. They may be given for 2 consecutive days (50 mg/m2 each day for a total dose 100 mg/m2), typically on days 1 and 2, or as a single dose, typically on day 1.
DRUG	Carboplatin	If cisplatin cannot be given at 100 mg/m2 for either cycle 1 or cycle 2, the investigator may use a regimen with carboplatin and 5-Fluorouracil in its place. Carboplatin will be given at a dose of AUC 1.25 intravenously daily x 4 days starting on day 1 of the cycle (total dose of AUC 5). Cycle 2 (Week 4): After the three weeks of radiation at week 4 when the subject no longer is receiving radiation therapy, subjects will receive cisplatin 100 mg/m2 intravenously. The may be given for 2 consecutive days (50 mg/m2 each day for a total dose 100 mg/m2), typically on days 22 and 23, or as a single dose, typically on day 22.
DRUG	5Fluorouracil	If cisplatin cannot be given at 100 mg/m2 for either cycle 1 or cycle 2, the investigator may use a regimen with carboplatin and 5-Fluorouracil in its place. 5-Fluorouracil will be given at a dose of 600 mg/m2 intravenous infusion over 24 hours daily x 4 days (total dose of 2400 mg/m2 intravenous infusion over 96 hours).
RADIATION	Proton Therapy	Proton beam using pencil beam delivery either with the Varian or IBA delivery systems will be allowed for Cohort B. Proton beam therapy will be given at the New York Proton Center in New York City, where MSKCC has a well-established business associate agreement and cooperative research agreement with, respectively. If treatment at NYPC is not feasible, patients may be referred to ProCure in Somerset, NJ.

Timeline

• Start date: 2017-10-16
• Primary completion: 2026-10-31
• Completion: 2026-10-31
• First posted: 2017-10-27
• Last updated: 2026-04-13

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study