Coorticosteroid Regimen in Patients With Anti-PD-1/PD-L1 Induced Pneumonitis

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective interventional open-label randomized trial. The patients treated with anti-

PD-1 (programmed-death receptor type 1) or anti-PD-L1 (programmed-death ligand) antibodies in case of new acute onset interstitial changes or new seriuos respiratory system related symptoms will be recruited for this study to perform diagnostics. At the recruitment the patient will be randomized 1:1 to investigatory or control arm, the randomization will be stratified upon three criteria:

1. severity of suspected pneumonitis at baseline (grade 2 vs. grade 3-4)

2. response for oncological treatment (partial response (PR) and complete response (CR) vs. stable disease (SD) and progression disease (PD))

3. chronic respiratory system disorders Both groups will be treated in the same way in terms of diagnostic procedures. In case of interstitial lung diseases related to immune checkpoint inhibitor is confirmed with the severity of grade 2-4 in the modified CTCAE criteria the patient will get the treatment, accordingly to the randomization: ARM A - INVESTIGATORY GROUP the start dose will be 1-4 mg/kg of body weight of prednisone, depending on clinical condition and pneumonitis severity, the induction treatment will last for 5-7 days, in case of severe condition - no improvement after 48-72 h of initial treatment - introduction of immunosuppressive agent is recommended - cyclophosphamide, mofetil mycophenolate or infliximab. A continuation treatment with dose tapering is than recommended, starting from 60mg q 24h of prednisone for 2-4 weeks, and dropping the dose 10mg q 24 h not faster than over 14 days; the maintenance dose of prednisone 10mg q 24 h should be hold for 8 weeks and withdraw should last for 4 weeks. This arm will be treated with corticosteroid for at least 12-24 weeks.

ARM B - CONTROL GROUP the starting dose will be 1-4mg/kg of body weight of prednisone , depending on clinical condition and pneumonitis severity, the induction treatment will last 5-7 days; in case of severe condition - no improvement after 48-72 h of initial treatment - introduction of immunosuppressive agent is recommended: cyclophosphamide, mofetil mycophenolate or infliximab. A continuation treatment with dose tapering is than planned, starting from oral dose of 30-60mg q 24h of prednisone, and dose reduction of 10mg q 24 h each 1 week. This arm will be treated for 6-12 weeks.

During the treatment and after its termination the function of respiratory system, interstitial changes in radiologic examinations, anticancer response, survival time, pneumonitis relapse and glucocorticosteroid side effects will be monitored and evaluated. The observation will last up to 52 weeks.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute for Tuberculosis and Lung Diseases, Poland
• Treatments: Prednisone

Criteria

Inclusion Criteria:

1. age over 18 years old

2. histological or cytological confirmation of solid cancer

3. treatment with anti-PD-1 or anti-PD-L1 antibody in monotherapy or in combination with cytotoxic chemotherapy or antiangiogenic agents like anti-vascular epitheliar growth factor antibodies

4. acute onset respiratory symptoms or lung changes in radiologic examinations which were not present before immunotherapy was introduced e. signed informed consent

Exclusion Criteria:

1. concomitant or previous treatment with anti-CTLA4 or other immunotherapeutic agents

2. active untreated tuberculosis

3. the use of glucocorticosteroids in the dose equivalent to 10mg q 24h or more of prednisone in the last 4 weeks in indication other than pneumonitis or different immune related adverse event d. withdraw of consent