Trial to evaluate how severe the side effects are and how well the addition of Nivolumab to standard treatment works in patients with advanced NSCLC.
- Conditions
- locally advanced stage IIIA/B NSCLCMedDRA version: 20.0Level: PTClassification code 10029520Term: Non-small cell lung cancer stage IIIASystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005097-11-BE
- Lead Sponsor
- ETOP (European Thoracic Oncology Platform)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 78
- Histologically or cytologically confirmed non small cell lung carcinoma
- Locally advanced stage IIIA or III B (T0-3 N2-3 or T4N0-3 M0) NSCLC, according to 7th TNM classification.
Within 35 days before beginning of first platinum-based chemotherapy cycle:
- Nodal status N2 or N3 must be proven (by biopsy, EBUS, mediastinoscopy or thoracoscopy) except for overt cT4 disease.
- Whole body FDG-PET CT plus contrast enhanced CT of thorax / upper abdomen (from top of thorax until adrenal glands, and full liver and kidney included) in addition to or in combination with PET.
- brain MRI (preferred) or high-quality brain CT with intravenous contrast at the time of staging mandatory
within 28 days before enrolment.
- Measurable disease (according to RECIST v1.1 criteria)
- Age: equal or greater than 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (see Table 1)
- Life expectancy > 3 months
- Previous delivery of a maximum of one 3-weekly cycle of platinum-based chemotherapy
- All AEs from previous therapies (including the first chemotherapy cycle in the context of this trial) resolved to grade <2 (except fatigue, alopecia, nausea, lack of appetite and peripheral neuropathy).
- Adequate haematological function:
- WBC: equal or greater than 2000/microL
- haemoglobin: equal or greater than 9 g/dL
- neutrophil Count: equal or greater than 1×109/L
- platelet Count: equal or greater than 100 × 109/L
- Adequate liver function:
- Total Bilirubin: equal or smaller than 2 x ULN (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dl)
- ALT: equal or smaller than 3 × ULN
- alkaline phosphatase equal or smaller than 5 x ULN.
- Adequate renal function: Calculated creatinine clearance ? 30 ml/min (according to Cockroft-Gault, see 10.2)
- equal or greater than 60ml/min for patient receiving cisplatin
- equal or greater than 30ml/min for patient receiving carboplatin
- Pulmonary function FEV1 of 1.0 l or > 40% predicted value and DLCO > 30% predicted value
- Patient capable of proper therapeutic compliance, and accessible to correct follow-up.
- Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before trial enrolment. The test must be repeated within 24 hours before beginning nivolumab treatment and then before every 2nd nivolumab administration. Pregnancy tests should be repeated at approximately 30 days and approximately 70 days after nivolumab treatment stops
- Written Informed Consent (IC) for trial treatment must be signed and dated by the patient and the investigator prior to any trial-related evalutation and/or intervention.
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 78
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 78
- Patient with mixed small-cell and non-small-cell histologic features
- Patient with pleural or pericardial effusions proven to be malignant
- Prior chemotherapy, radiotherapy or molecular targeted therapy for NSCLC (with the exception of one cycle of chemotherapy given prior to enrolment into this trial, see 7.1.7)
- Patient with an active, known or suspected autoimmune disease. Patients are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- Patient who has had in the past 3 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast.
- Patient with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient?s capacity to participate in the trial..
- Ongoing clinically serious infections requiring systemic antibiotic or antiviral, antimicrobial, antifungal therapy.
- Known or suspected hypersensitivity to nivolumab or any of its excipients
- History of severe hypersensitivity reaction to any monoclonal antibody
- Substance abuse, medical, psychological or social conditions that may interfere with the patient`s participation in the trial or evaluation of the trial results.
- Established pathological diagnosis of underlying interstitial lung disease or pulmonary fibrosis
- Women who are pregnant or in the period of lactation
- Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method (see section 10.8) during the trial treatment and for a period of at least 7 months (male participants) and 5 months (female participants) following the last administration of nivolumab.
- Patients receiving any concurrent anticancer systemic therapy
- HIV, active Hepatitis B or Hepatitis C infection
- Previous radiotherapy to the thorax (prior to inclusion), including radiotherapy for breast cancer
- Planned radiotherapy to lung of mean dose > 20 Gy or V20 > 35 %
- Patient who received treatment with an investigational drug agent during the 3 weeks before enrolment in the trial
- Metastatic disease (mandatory assessment of the brain either by MRI or high-quality CT with intravenous contrast at the time of staging as well as systemic PET and CT scan)
- 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 costimulation or immune checkpoint pathways
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and efficacy of the concurrent nivolumab administration with standard fist-line chemotherapy and radiotherapy in locally advanced stage IIIA/B NSCLC, as defined by the rate of grade (equal or greater than) 3 pneumonitis (CTCAE V4.0) 6 months post-radiotherapy and, if safety is proven, to assess the progression-free survival.;Secondary Objective: - To evaluate secondary measures of clinical efficacy including time to first pneumonitis of equal or greater than 3, 1-year progression-free survival, objective response rate (ORR), time to treatment failure (TTF) and overall survival (OS). <br><br>- To assess the safety and the tolerability of the Treatment.;Primary end point(s): Grade equal or greater than 3 pneumonitis (CTCAE V4.0);Timepoint(s) of evaluation of this end point: It will be used as the primary endpoint for all patients followed for at least 6 months from end of radiotherapy.
- Secondary Outcome Measures
Name Time Method