In this multi-institution phase I/II trial, the investigators have chosen paclitaxel and carboplatin using a schedule and doses identical to those used in the CROSS trial. Following a run-in with nivolumab alone at 240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care established by the CROSS trial: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks. Concurrent radiation will be administered with chemotherapy at 1.8 Gy/fraction × 28 fractions to a total dose of 50.4 Gy, the standard radiation dose administered in the United States for trimodality therapy that includes concurrent therapy with carboplatin and paclitaxel. A decrease in dose to 41.4 Gy per the protocol established by van Hagen, et al. will be permitted before discontinuing therapy due to unacceptable toxicity. While the CROSS study administered only 5 weekly doses of chemotherapy during the 5 weeks of radiation, the higher dose of 50.4 Gy (1.8 Gy/fraction ×28 fractions over 5½ weeks) utilized in this study permits for a sixth dose during the additional week of radiation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).
University of Califonia, San Diego
La Jolla, California, United States
University of Southern California
Los Angeles, California, United States
New York University School of Medicine
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Oregon Health Sciences University
Portland, Oregon, United States
Phase 1: Number of Unacceptable Toxicity (UT) Events
UT is defined as: 1. Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy) 2. any toxicity that results in a \> 2-week delay in chemoradiation
Time frame: 92 days (up to 28 days after Day 64)
Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)
Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue
Time frame: 5-8 Weeks post radiation treatment (7-8 months after treatment start)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.