Advanced stage (IIIB/IV) squamous non-small cell lung cancer (NSCLC) MedDRA version: 20.0 Level: PT Classification code 10025124 Term: Lung squamous cell carcinoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10025125 Term: Lung squamous cell carcinoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: OPDIVO - 10 MG/ML- CONCENTRATO PER SOLUZIONE PER INFUSIONE- USO ENDOVENOSO- FLACONCINO (VETRO)- 10 ML- 1 FLACONCINO
Product Name: OPDIVO
Product Code: MDX1106
Pharmaceutical Form: Solution
Sponsors
GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Pathologically (histology or cytology) confirmed diagnosis of squamous NSCLC • Subjects with histologically or cytologically confirmed stage IIIB-IV or recurrent squamous NSCLC with partial response (PR), complete response (CR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, after 4-6 courses of standard platinum-based chemotherapy (i.e. cisplatin or carboplatin combined with either paclitaxel, docetaxel, nab-paclitaxel, gemcitabine or vinorelbine) • Male or female and = 18 years of age • Life expectancy = 12 weeks • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 • Patients must have completed the last chemotherapy course within 8 weeks before randomization and have performed radiological assessment for evaluating tumor response to first-line chemotherapy within 4 weeks before randomization • Patients with treated brain metastases with stable lesions for at least 4 weeks and off steroids or on a stable dose of steroids (= 10 mg of prednisone or equivalent). Radiotherapy must have been completed a minimum of 14 days prior to randomization, and patients must have recovered from AEs related to radiotherapy to < grade 1 (except alopecia) • For Females: must be postmenopausal (defined as occurring 12 months after last menstrual period) before the screening visit, or are surgically sterile. Women of childbearing potential (WOCBP) must use 2 effective methods of contraception, from the time of signing the informed consent form (ICF) through 30 days after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. Furthermore, they should avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug. 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 Nivolumab. • For Males: even if surgically sterilized (i.e. post-vasectomy status) agree to practice effective barrier contraception, with a failure rate of less than 1% per year, during the entire study treatment period and for a period of 31 weeks after the last dose of investigational product, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject • Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization: o Absolute neutrophil count (ANC) = 1000/mm3, platelet count = 75.000/mm3 and haemoglobin 9 g/dL o Total bilirubin = 1.5 the institutional upper limit of normal (ULN), except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL o Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 3 the institutional ULN (= 5 if liver function test elevations are due to liver metastases) o Creatinine = 1.5 institutional ULN or estimated creatinine clearance of = 30 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft-Gault formula) • Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before randomization, and otherwise noted in other inclusion/exclusion criteria • Recovered (i.e., = Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia • Ability to c
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria are not eligible to the study: • Prior treatment with Nivolumab or any other immunotherapy agent (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways). • Patients with progressive disease after 4-6 cycles of first-line platinum-based chemotherapy or subjects who received non-platinum-based first-line chemotherapy • 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 enrol. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted. Adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted • Patients with symptomatic and/or progressive brain metastases or with carcinomatous meningitis. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) or computed tomography (CT) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of Nivolumab administration. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) • As there is potential for hepatic toxicity with Nivolumab or Nivolumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with Nivolumab-containing regimen • Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period • Any comorbid condition or unresolved toxicity that would preclude administration of Nivolumab • Any medical condition, within 6 months before receiving the first dose of study drug, considered relevant by investigator. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. Patients with a pacemaker may be enrolled in the study upon discussion with the project clinician • Infection requiring IV antibiotic therapy or other serious infection within 14 days before the first dose of study drug • For female subjects: positive serum pregnancy test, pregnancy or breast feeding • Major surgery within 4 weeks (or 2 weeks for a minor surgery) before study enrolment and not fully recovered to baseline or to a stable clinical status. Insertion of a vascular device is allowed • Subjects with interstitial lung disease that is symptomatic or may interfere with the de
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare early switch maintenance vs standard BSC and delayed second-line Nivolumab in terms of overall survival (OS) in patients with squamous NSCLC with non-progressive disease after standard first-line platinum-based chemotherapy. ;Secondary Objective: -To compare Nivolumab with standard BSC in terms of progression-free survival (PFS) -To compare Nivolumab with standard BSC in terms of progression-free survival from induction (PFSind) -To compare Nivolumab with standard BSC in terms of time to treatment failure (TTF) -To compare Nivolumab with standard BSC in terms of overall Survival from induction (OSind) ;Primary end point(s): The primary end-point is OS that will be measured from the date of randomization to the date of death by any cause.;Timepoint(s) of evaluation of this end point: From the date of randomization to the date of death by any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Progression-Free Survival (PFS) that will be defined as the time from randomization until objective tumor progression or death by any cause. 2) Progression-Free Survival from induction (PFSind) that will be defined as the time from first chemotherapy cycle until objective tumor progression or death by any cause. 3) Time to Treatment Failure (TTF) that will be defined as the time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient’s preference, investigator’s decision or death. 4) Overall Survival from induction (OSind) that will be defined as the time from first chemotherapy cycle until death by any cause.;Timepoint(s) of evaluation of this end point: 1) the time from randomization until objective tumor progression or death by any cause. 2) the time from first chemotherapy cycle until objective tumor progression or death by any cause. 3) the time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient’s preference, investigator’s decision or death. 4) the time from first chemotherapy cycle until death by any cause. | — |
Countries
Italy
Contacts
Public ContactProject Manager Studio
GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica)
Outcome results
None listed