Immunotherapy With Chemotherapy and Chemoradiation for Advanced Squamous Cancer of Nasal Cavity / Paranasal Sinuses (I-NAPA)

Study Overview
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Brief Summary
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This is a single arm phase II study that will evaluate the combination of pembrolizumab, docetaxel, and cisplatin or carboplatin (PDC) as single treatment modality in patients with stage II-IVb (T2-4, any N, M0) squamous cell carcinoma of the nasal cavity/paranasal sinuses (PNS SCC).

Detailed Description
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Primary Objective -Increase overall response rate (ORR), following pembrolizumab combined with induction chemotherapy prior to radiation, from historical 60% with induction chemotherapy alone to 80%. Secondary Objective Improve the following efficacy endpoints relative to historical results with chemotherapy alone: progression free survival (PFS), overall survival (OS), organ [orbital, maxillary, cranial] preservation rate (OPR), and locoregional failure (LRF). To determine safety and tolerability of pembrolizumab combined with induction chemotherapy and chemoradiation in patients with PNS SCC. Correlate immune phenotype in tumors and blood, including T cell infiltration and PD-L1 status, with treatment outcomes.

Official Title
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Immunotherapy With Chemotherapy and Chemoradiation for Advanced Squamous Cancer of Nasal Cavity / Paranasal Sinuses (I-NAPA)

Conditions
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Squamous Cell Carcinoma, the Nasal Cavity, Paranasal Sinuses

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Docetaxel
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female participants who are at least 18 years of age on the day of signing informed consent with newly diagnosed, previously untreated, histologically and/or cytologically confirmed diagnosis of Stage II-IVb PNS SCC will be enrolled in this study. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 150 days after the last dose of study treatment and refrain from donating sperm during this period. -Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 150 days after the last dose of study treatment. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. Have measurable disease based on RECIST 1.1. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Have adequate organ function as defined in the following table (Table 1). Blood must be collected within 14 days prior to the start of study treatment. Exclusion Criteria: A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). Patients must not have received prior systemic anti-cancer therapy including investigational agents or radiation therapy for PNS SCC but could have received treatment for prior cancers if greater than 2 years (refer to Item 8 for further details).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: pembrolizumab, docetaxel, and cisplatin or carboplatin<br>IV | Drug: Pembrolizumab<br>* given by IV<br>Drug: Docetaxel<br>* given by IV<br>Drug: Cisplatin<br>* given by IV<br>Drug: Carboplatin<br>* given by IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To increase overall response rate (ORR) |  | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To improve the following efficacy endpoints relative to historical results with chemotherapy alone |  | through study completion, an average of 1 year | 
| To determine the safety of pembrolizumab combined with induction chemotherapy and chemoradiation in patients with PNS SCC |  | through study completion, an average of 1 year | 
| To determine the tolerability of pembrolizumab combined with induction chemotherapy and chemoradiation in patients with PNS SCC |  | through study completion, an average of 1 year |