metastatic non-squamous Non-Small Cell Lung Cancer (Lung adenocarcinoma metastatic and Large cell lung cancer metastatic) MedDRA version: 21.1 Level: PT Classification code 10069730 Term: Large cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10064049 Term: Lung adenocarcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (inc
Conditions
Interventions
Trade Name: Opdivo (R)
Product Name: Nivolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NIVOLUMAB
CAS Number: 946414-94-4
Concentration unit: mg/ml milligram(s)/
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years at time of study entry. 2. ECOG performance status 0-1. 3. Patients with metastatic non-squamous non-small cell lung cancer after failure of platinum-based doublet chemotherapy and a) no necessity of radiotherapy (group B) or b) the necessity of radiotherapy of a metastatic bone lesion or soft tissue lesion (group A) 4. Patients must have measurable disease by CT or MRI per RECIST 1.1 criteria. 5. For each patient a formalin fixed, paraffin-embedded tumor tissue block (archival or recent) or a minimum of 15 unstained slides of tumor sample (2-3 µm sections; slices must be recent and collected on slides provided by the sponsor) must be available for biomarker (PD-L1) evaluation. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 1. Patients who require ongoing treatment with more than 10-mg of prednisone (or steroid equivalent, excluding inhaled or topical steroids) daily. 2. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 3. Patients with an active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids/immunosuppressive medications EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger. (Subjects with type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders, (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll.) 4. Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy 5. 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. 6. Brain metastases mandating active treatment in terms of WBI (whole brain irradiation or stereotactic brain irradiation). 7. Subjects with brain metastases are eligible if metastases have been treated and treatment has been completed at least 12 weeks before inclusion in this study for group B and 2 weeks for group A. Moreover, there must be no magnetic resonance imaging (MRI) evidence of progression within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. Patients with stable/asymptomatic brain metastases that do not require local therapy with irradiation (whole brain irradiation or stereotactic brain irradiation) can be included. In ambiguous cases, consultation with the LKP or any authorized person ist advised 8. Known activating EGFR mutation or a known ALK translocation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate clinical efficacy of a nivolumab-radiotherapy combination treatment..;Secondary Objective: Secondary objectives: • information on safety and tolerability of nivolumab in combination with radiotherapy by measurement of incidence and severity of AEs and specific laboratory abnormalities in all treated subjects by subject subgroups • further efficacy data will in patients without necessity of radiotherapy • information on individual, patient reported and investigator-assessed quality of life • To explore immune related RECIST criteria as an evaluation method for clinical benefit of nivolumab and nivolumab/radiotherapy Exploratory objectives: • Tissue collection and blood sampling whilst course of disease to explore potential predictors of response to nivolumab • To address the role of radiotherapy in the context of immune modulation, several aspects of radiation planning and treatment are planned to be explored;Primary end point(s): • ORR according to RECIST 1.1 criteria;Timepoint(s) of evaluation of this end point: approx. 36 months after FPI, approx. 6 months after LPI | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS • PFS and ORR using assessment according to irRECIST • OS • 1 year OS rate • Descriptive subgroup analyses of efficacy in relation to PD-L1 expression levels (e.g. cut-off 1%, 5%, 10%) • Treatment Emergent Adverse Events according to CTC 4.03 • Frequency of abnormal laboratory parameters • QoL [FACT-L];Timepoint(s) of evaluation of this end point: approx. 48 months after FPI | — |
Countries
Germany
Contacts
Public ContactAIO-Studien-gGmbH
AIO-Studien-gGmbH
Outcome results
None listed