SBRT With Immunotherapy in Early Stage Non-small Cell Lung Cancer: Tolerability and Lung Effects

Sponsor
Royal Marsden NHS Foundation Trust
Study ID
NCT03383302
Phase
PHASE1/PHASE2
Status
Completed

Conditions

  • Non-small Cell Lung Cancer Stage I
  • Non-small Cell Lung Cancer Stage II

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Stereotactic body radiotherapy — RADIATION
    Patients will receive a total of 54 Gy if delivered in 3 fractions, 55 Gy if delivered in 5 fractions or 60 Gy if delivered in 8 fractions.
  • Nivolumab — DRUG
    Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody, that binds to the PD-1 receptor and blocks interaction with its ligands PD-L1 and PD-L2. Nivolumab will be administered intravenously at a flat dose of 240 mg q2w over 30 minutes for 13 cycles followed by 480mg q4w over 60 minutes for 7 cycles, until 20 cycles in total to complete (a minimum of 1 year of treatment if no delays are encountered).

Study Details

This is a single arm, multi-centre, phase II open label study of nivolumab with stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer. SBRT will be delivered in either 3 or 5 fractions for peripheral disease or 8 fractions in central disease. A flat dose of 240 mg nivolumab infusion will begin after the final fraction of SBRT, within 24 hours and typically on the same day. Nivolumab will subsequently be given every 2 weeks at a flat dose of 240 mg for a further 13 cycles followed by Nivolumab 480mg Q4W for 7 cycles until 20 cycles in total are complete, unless any study drug discontinuation criteria are met. Treatment (20 cycles) will take a minimum of 1 year to complete but may exceed this timeframe if treatment delays are encountered. (Patients who have enrolled on Nivolumab Q2W 240mg regimen for 26 cycles and are beyond cycle 14 will receive 26 cycles Q2W in total to complete treatment). Assessment of toxicities will be performed at each clinic visit during treatment, at 30 days after the final nivolumab infusion and until 100 days after the final nivolumab infusion. Changes in spirometry values and PFTs will be assessed throughout the trial. Relapse rates will be assessed with staging CT scans at 3, 6, 12, 18 and 24 months post SBRT. An exploratory assessment will be made of the effect pre-treatment pulmonary function tests (PFTs) have on outcome measures.

Key Dates

Start date
Feb 8, 2018
Status verified
Jul 2025
Primary completion
Aug 12, 2024
Completion
Jun 26, 2025

Study Design

Enrollment
29 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Arm 1 Tolerabilty
    This is a single arm study of nivolumab administered on completion of stereotactic body radiotherapy (SBRT) to patients with early stage NSCLC. The first 5 patients to enroll must have Eastern Co-operative Oncology Group (ECOG) performance status \< 2 at the time of first dose of investigational medical product (IMP). An Independent Data Monitoring Committee (IDMC) will meet when the first 5 patients have reached 3 months follow up from their 1st dose of nivolumab or have withdrawn consent to follow-up. The IDMC, if satisfied with the safety data from the initial 5 patients, may recommend escalation to include recruitment of patients with ECOG performance status of 2.

Primary Outcome Measure

Assessment of lung toxicity (pneumonitis) from treatment with Nivolumab after SBRT for early stage NSCLC [ Time Frame: Six months from final dose of SBRT administered for each patient ]

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