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A study combining 2 medications against cancer (Nivolumab and Celecoxib)

Phase 1
Conditions
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
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2019-000572-41-BE
Lead Sponsor
Cliniques Universitaires Saint-Luc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
68
Inclusion Criteria

1. Men and women = 18 years of age.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
3. Measurable disease as per RECIST 1.1.
4. Adequate renal, hepatic and hematologic functions as defined by laboratory parameters within = 7 days before treatment initiation.
- Platelet count =100x103/µL
- Leukocyte count = 3x103/µL
- Hemoglobin = 9 g/dL
- ASAT and ALAT = 2xULN
- Serum creatinine =1.5xULN
- Total bilirubin = 1.5xULN
- LDH = 1.5xULN
5. Viral serology : negative antibodies for HCV and HIV; negative antigens for HBV
6. Metastases biopsiable on two occasions
7. Patients should agree to perform biopsies and blood collections for translational research
8. 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 IDO positive (=5% expression of tumor cells) and non T-cell infiltrated tumors (<1% T cells infiltrating
the tumor bed).
9. Signed informed consent from the patient or legal representative must be obtained.
10. Cancer types with an indication of treatment with anti-PD1 antibodies such as
- Melanoma non BRAF mutated in first line
- Melanoma BRAF mutated in first or second line
- Lung cancer (NSCLC) in second line of treatment
- Renal cell Cancer (RCC) in second line
- Head and Neck squamous carcinoma (HNSC) after platinum salt based chemotherapy
- Bladder cancer after platinum salt based chemotherapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

1. Active brain metastases or leptomeningeal metastases.
2. Ocular melanoma
3. 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 conditions not expected to
recur in the absence of an external trigger are permitted to enroll.
4. Clinically significant cardiovascular disease (including cardiac insufficiency NYHA grade III and IV, unstable angina, arrythmia, myocardial infarction, symptomatic congestive heart failure) in the past 12 months before enrollment
5. Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders or other conditions requiring concurrent medications not allowed during this study
6. Concomitant chemotherapy or radiotherapy for curative intent.
7. Administration of anti-angiogenic drugs or immunomodulatory agents.
8. Pregnancy or breast-feeding or planning to become pregnant within 6 months after the end of treatment.
9. Subject (male or female) not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months after the end of treatment.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Safety Run-in : To assess the safety and tolerability of celecoxib in combination with anti-PD1 antibodies<br>Phase II : To evaluate the objective response rate (ORR) of celecoxib in combination with anti-PD1 antibodies<br>;Secondary Objective: To assess the safety and tolerability of celecoxib in combination with anti-PD1 antibodies<br>To evaluate the anti tumor effect of celecoxib in combination with anti-PD1 antibodies<br><br>Exploratory : To determine whether this treatment results in decreased tumoral IDO1 expression and increased tumoral infiltration by<br>T cells.;Primary end point(s): Overall response rate (ORR), defined as the percentage of subjects having a complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per RECIST v1.1.;Timepoint(s) of evaluation of this end point: week 12
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Safety, tolerability of celecoxib in combination with anti-PD-1 antibodies, as assessed by AEs, clinical laboratory tests, physical examination results using CTC-NCIv4.03.;Timepoint(s) of evaluation of this end point: up to progression of disease or until end of treatment (maximum of 2 years)
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