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An Exploratory Study of the Biologic Effects and Biomarkers of Nivolumab in combination with Ipilimumab in Subjects with Treatment-Naive Stage IV or recurrent Non-Small Cell Lung Cancer (NSCLC) - CA209592

Studio Clinico

Patologia: Neoplasie del polmone

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Prima linea

Criteri di inclusione: 

1) Signed Written Informed Consent
    a) Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
    b) Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
2) Type of Participant and Target Disease Characteristics
    a) Subjects with histologically confirmed Stage IV or recurrent NSCLC (per the 7th International Association for the Study of Lung Cancer classification [Goldstraw 2007]), squamous or non-squamous histology, with no prior systemic anticancer therapy (including EGFR and ALK inhibitors) given as primary therapy for advanced or metastatic disease.
Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration of the prior regimen occurred at least 6 months prior to enrollment.
Prior chemoradiation for locally advanced disease is also permitted as long as the last administration of chemotherapy or radiotherapy (which ever was given last) occurred at least 6 months prior to enrollment.
    b) Measurable disease by CT or MRI per RECIST 1.1 criteria. Tumor assessment performed within 28 days of start of study treatment.
    c) All participants must have tissue submitted during screening. This may include either a formalin-fixed paraffin-embedded (FFPE) tissue block or a minimum of 15 unstained tumor tissue slides.
    Part 1: For cohort assignment purposes (PD-L1 status determination), archival tissue samples ≤ 3 months old will be allowed to determine PD-L1 IHC results. Fresh pre-dose biopsy samples (5 cores: 3 in FFPE and 2 in HypoThermosol®) will still need to be
submitted.
    Part 2: a fresh biopsy (preferred) or archival sample (≤ 3 months old) is required for enrollment, but treatment may start before test results are received.
    d) ECOG Performance Status 0 or 1.
3) Age and Reproductive Status
    a) Males and Females, ages 18 years (or age of majority) and older.
    b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
    c) Women must not be breastfeeding.
    d) Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment followed by a period of 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo five half-lives. WOCBP treated with nivo + ipi combination should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
    e) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment followed by a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo five half-lives. Males treated with nivo + ipi combination who are sexually active with WOCBP must continue contraception for 7 months (90 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational
drug. In addition, male participants must be willing to refrain from sperm donation during this time.
f) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.

Criteri di esclusione: 

1) Medical Conditions
a) Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded. All subjects with non-squamous histology must have been tested for EGFR mutation status; use of an FDA-approved test is strongly encouraged. Non-squamous subjects with unknown or indeterminate EGFR status are excluded.
b) Subjects with known ALK translocations which are sensitive to available targeted inhibitor therapy are excluded. If tested, use of an FDA-approved test is strongly encouraged. Subjects with unknown or indeterminate ALK status may be enrolled.
c) Subjects with untreated CNS metastases are excluded.
    i) Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, participants
must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment assignment.
d) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
e) Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
f) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses < 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
g) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
h) Subjects with serious or uncontrolled medical disorders and any known medical condition that, in the investigator’s opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
i) Subjects with a known history of a positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
2) Prior/Concomitant Therapy
a) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
b) Treatment with botanical preparations (eg herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
3) Physical and Laboratory Test Findings
Screening laboratory values that meet the following criteria (using CTCAE v4):
a) WBC < 2000/μL
b) Neutrophils < 1500/μL
c) Platelets < 100 x 103/μL
d) Hemoglobin < 9.0 g/dL
e) Serum creatinine > 1.5 x ULN, unless creatinine clearance ≥ 40 mL/min (measured or calculated using the Cockroft-Gault formula)
f) AST > 3.0 x ULN
g) ALT > 3.0 x ULN
h) Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0x ULN).
i) Any positive test for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g. Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative)
4) Allergies and Adverse Drug Reaction
a) History of allergy or hypersensitivity to study drug components.
5) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Bristol-Myers Squibb approval is required.)
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Trattamento sperimentale: 

nivolumab + ipilimumab

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- To evaluate baseline tumor mutation burden as a candidate biomarker of clinical efficacy of nivolumab and ipilimumab combination therapy.
- To investigate the potential association between candidate biomarkers in peripheral blood and tumor tissue at baseline and on-treatment with clinical efficacy measures

Obiettivi secondari dello studio: 

To evaluate efficacy in patient subgroup defined by baseline discovery biomarkers.

Centri partecipanti

Nord Italia

Ospedale Papa Giovanni XXIII Bergamo
Piazza OMS 1 - 24127 Bergamo - BG

Riferimento: Dr.ssa Lucia Bonomi

 

Azienda Ospedaliero-Universitaria di Parma
Via Gramsci 14 - 43126 Parma - PR

Riferimento: Dr. Marcello Tiseo
Telefono: 0521702316

 

Centro Italia

Azienda Ospedaliera di Perugia
Via Dottori 1 - 06132 Perugia - PG

Riferimento: Dr. Vincenzo Minotti
Telefono: 0755784212
Email: vinminotti@yahoo.it

 

Sud Italia e isole

AOU Policlinico Vittorio Emanuele PO G. Rodolico
Via S. Sofia 78 - 95123 Catania - CT

Riferimento: Dr. Hector Jose Soto Parra
Telefono: 0953781496
Email: hsotoparra@yahoo.it

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2018-000462-11

Data di inserimento: 06.11.2018

Promotore

Bristol-Myers Squibb

CRO

/

Principal Investigator ITALIA

Azienda Ospedaliera di Perugia

Riferimento: Dr. Vincenzo Minotti

Telefono: 0755784212

Email: vinminotti@yahoo.it

Localita: Perugia

 

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