An Open Label Phase II Study Combining Nivolumab and Celecoxib in Patients With Advanced  Cold  Solid Tumors

Study Overview
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Brief Summary
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This is an open-label study to evaluate the safety and the anti-tumor activity of the combination of nivolumab and celecoxib. The total numbers of participants to be enrolled will be up to 68 participants, depending on the investigated dose of celecoxib during the safety run-in phase.

Official Title
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NICE-COMBO: An Open Label Phase II Study Combining Nivolumab and Celecoxib in Patients With Advanced  Cold  Solid Tumors

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Drug: Celecoxib 400 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years of age. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Measurable disease as per RECIST 1.1. Adequate renal, hepatic and hematologic functions as defined by laboratory parameters within ≤ 7 days before treatment initiation. Metastases biopsiable on two occasions Recently acquired (within 90 days prior to treatment) tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. In order to include only IDO1 positive (≥5% expression of tumor cells) and non T-cell infiltrated tumors (<1% T cells infiltrating the tumor bed) Cancer types with an indication of treatment with anti-PD1 antibodies such as Melanoma non BRAF mutated in first line of treatment Melanoma BRAF mutated in first or second line of treatment Lung cancer (NSCLC) in second line of treatment Renal cell Cancer (RCC) in second line of treatment Head and Neck squamous carcinoma (HNSC) after platinum salt based chemotherapy Bladder cancer after platinum salt based chemotherapy Exclusion Criteria: Active brain metastases or leptomeningeal metastases. Ocular melanoma. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic treatment, or other autoimmune condition not expected to recur in the absence of an external trigger are permitted to enroll. Subjects must also meet other study criteria including exclusions for medical history, positive Hep B/C, HIV, and pregnancy tests, and other laboratory criteria.

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
Interventional Model Description: Simon's two-stage Minimax design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Group<br>Celecoxib 400 mg/d Nivolumab 240 mg q2w | Drug: Celecoxib 400 mg<br>* Celecoxib 400 mg/day in combination with nivolumab fixed dose<br>* Other names: Nivolumab 240 mg q2w;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | To evaluate the objective response rate (ORR) of Celecoxib in combination with anti-PD1 antibodies | at week 12 from onset of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | All the patients that will receive at least one dose of nivolumab and celecoxib are assess for toxicity endpoint. All adverse events will be recorded and graded based on the CTCAE v4.0 scale. antibodies | from first dose to day 28 post last dose | 
| Efficacy - Duration of response (DOR) | defined as the time from earliest date of CR or PR (as determined by investigator assessment of radiographic disease burden per RECIST v1.1) until the earliest date of disease progression or death, due to any cause, if occurring sooner than disease progression. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 
| Efficacy - Time to response (TTR) | defined as the time from the date of first dose of study drug until the time of the earliest date of CR or PR (as determined by investigator assessment of radiographic disease burden per RECIST v1.1. | From onset of treatment to response of cancer through study completion, an average of 12 months is expected | 
| Disease control rate (DCR) | defined as the percentage of subjects having CR, PR, or stable disease (SD) for at least 8 weeks, as determined by investigator assessment of radiographic disease as per RECIST v1.1. | at week 12 from onset of treatment | 
| Progression-free survival (PFS) | defined as the time from the date of first dose of study drug until the earliest date of disease progression (as determined by investigator assessment of radiographic disease burden per RECIST v1.1), or death due to any cause, if occurring sooner than progression. | From date of randomization until the date of first documented progression or date of death, whichever comes first, assessed up to 60 months | 
| Overall survival (OS) | defined as the time from the date of first dose of study drug until death, due to any cause. | From date of randomization until the date of death, assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nivolumab, Celecoxib