Single-arm, two-part, phase IB safety study that uses a Bayesian Optimal Interval (BOIN-12) dose-escalation scheme.
Part 1 (Dose Finding) - Sentinel start at 9 Gy × 3 followed by fixed 3-patient BOIN cohorts exploring 8 Gy × 3 → 9 Gy × 3 → 10 Gy × 3. Target DLT rate θ = 0.20; ≈ 7-15 participants.
Part 2 (Expansion) - Additional enrolment at the selected maximum tolerated dose (MTD) until ≈ 30 evaluable subjects (Parts 1 + 2 combined). Patients receive peaks to the primary tumor alone (Group A) or to the primary + involved nodes (Group B) at the investigators' discretion (non-random).
Surgery occurs 6-8 weeks after RT; adjuvant therapy is pathology-driven.
Non-metastatic, pathologically confirmed oral cavity squamous cell carcinoma, cT3-T4a cN0-N3 or cT1-T2 cN1-N3. Histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma, e.g.). Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oral cavity (oral tongue, floor of mouth, alveolar ridge, buccal or lip, i.e.)
Surgically resectable
Zubrod Performance Status of 0-1
(Phase I) Primary and lymph node ≥ 3 cm
Cancers considered to be primarily located in the oropharynx even if p16 negative
Carcinoma of the neck of unknown primary site origin (even if p16 negative)
Distant metastasis or adenopathy below the clavicles;
Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease.
Factorial
Chemotherapy
DrugPatients receive standard induction chemoimmunotherapy (carboplatin, paclitaxel, and pembrolizumab) in three 21-day cycles, beginning on Day 1.
Lattice Radiotherapy (LRT)
RadiationLRT is administered concurrently with the first cycle of chemoimmunotherapy according to the dose-finding rules
Maximum tolerated dose (MTD) of pre-operative lattice radiotherapy delivered with chemoimmunotherapy
The BOIN (Bayesian Optimal Interval) algorithm will declare the MTD once a dose has an observed dose-limiting toxicity (DLT) rate compatible with the target toxicity level (θ = 0.20) and all higher doses are ruled out for excess risk.
Percentage of participants with complete pathologic response (pCR)
Percentage of participants with major response
Defined as ≤ 10 % viable tumor.
Percentage of participants with macroscopic residual disease
Defined as \> 10 % viable tumor.
Progression-free survival (PFS)
Time from Day 1 of protocol therapy to locoregional or distant progression or death, estimated with Kaplan-Meier methods.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
