lung cancer lung carcinoma
Conditions
Interventions
In the first 6 weeks, all patients will undergo treatment with the combination
of ipilimumab (IPI, 1mg/kg on day 1), nivolumab (NIVO
240mg, q2w) and
medium-dose multi-site hypofractionated radiotherapy (using 8Gy fractions on
days 8, 10 and 12). After this 6 week treatment period, and if no disease
progression is observed, patie
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed NSCLC, negative for EGFR, ALK or other treatable oncogenic drivers 2. WHO PS 0-2 3. Be willing and able to provide written informed consent for the trial. 4. Be above 18 years of age on day of signing informed consent. 5. Patients must have radiological disease progression on chemo-pembrolizumab 6. Have at least 1 lesion (up to 4) that is amenable to treatment with radiotherapy (3x8Gy as per judgement of the radiation oncologist), and at least 1 other unirradiated lesion which can serve as a measurable lesion for assessing tumor response based on RECIST 1.1. 7. Demonstrate adequate organ function, as deemed acceptable by the treating physician in the context of metastatic NSCLC
Exclusion criteria
Exclusion criteria: 1. Patients with fast progressive disease as per judgement of the treating physician. 2. Patients who had received any radiotherapy during previous treatment with chemo-pembrolizumab. 3. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. 4. Active autoimmune disease requiring systemic steroid treatment within the past 3 years or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids. 5. Evidence of interstitial lung disease or active, non-infectious pneumonitis. 6. Active infection requiring systemic therapy. 7. A history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 8. Active Hepatitis B or C. 9. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 10. Has received prior therapy with an anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways (except pembrolizumab). 11. Has developed immune related adverse events on immunotherapy that necessitated stopping pembrolizumab indefinitely. 12. Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety will be defined as (i) the percentage of patients with adverse events (NCI CTCAE), the grade and the relationship to IPI/NIVO/mRT will be assessed. Tumor responses will be assessed by ORR and DCR, overall and per study group. Clinical outcome parameters such as PFS, and OS at 1 and 2 years, will be registered. | — |
Secondary
| Measure | Time frame |
|---|---|
| - | — |
Countries
Netherlands
Outcome results
None listed