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

NCT04036721 | Suspended Phase 4 DMC

• 1 other identifier: KB-57/2019
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief 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. 1.severity of suspected pneumonitis at baseline (grade 2 vs. grade 3-4)
2. 2.response for oncological treatment (partial response (PR) and complete response (CR) vs. stable disease (SD) and progression disease (PD))
3. 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.

Conditions

Lung Neoplasm Malignant; Interstitial Lung Disease

Keywords

anti-PD-1; anti-PD-L1; pneumonitis; NSCLC; treatment; programmed-death receptor

Outcome Measures

Primary Outcomes (3)

• Pneumonitis relapse

  Incidence of pneumonitis relapse in study arm A vs. control arm B

  12 months

• Pneumonitis related deaths

  Incidence of pneumonitis related deaths in arm A vs. arm B

  12 months

• Radiological regression of pneumonitis

  Computed tomography assesment of pneumonitis regression, compared to initial examination. 4-point scale: coplete regression, definite partial response, slight partial response, progression.

  12 weeks and 52 weeks

Secondary Outcomes (3)

• Overall survival

  12 months

• Progression-free survival

  12 months

• Incidence of treatment related adverse events.

  12 months

Other Outcomes (1)

• Diagnostic procedure evaluation

  1 week

Study Arms (2)

ARM A - PROLONGED

EXPERIMENTAL

induction dose 1-4mg/kg of prednisone, prednisone 60mg q24h for 2-4wks, tapering not faster than 10mg each 14d, maintenance dose 10mg q24h for 8wks, withdraw of treatment during 4wks, summary of treatment time not shorter than 12-24wks.

Drug: Prolonged glucocorticosteroid (prednisone) regimen

ARM B - FAST REDUCTION

ACTIVE COMPARATOR

induction dose 1-4mg/kg of prednisone, prednisone 30-60 mg q24h, tapering not faster than 10mg each 7d, summary of treatment time 6-12wks.

Drug: Short glucocorticosteroid (prednisone) regimen

Interventions

Prolonged glucocorticosteroid (prednisone) regimen DRUG

Prolongation of maintenance therapy with prednisone of patients with pneumonitis inducted by anyi-PD-1/anti-PD-L1 antibodies.

ARM A - PROLONGED

Short glucocorticosteroid (prednisone) regimen DRUG

Prednison regimen based upon American Society of Clinical Oncology and European Society for Medical Oncology Clinical Practice Guidelines on pneumonitis treatment in patients receiving immunotherapy agents

ARM B - FAST REDUCTION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age over 18 years old
• histological or cytological confirmation of solid cancer
• 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
• acute onset respiratory symptoms or lung changes in radiologic examinations which were not present before immunotherapy was introduced e. signed informed consent

You may not qualify if:

• concomitant or previous treatment with anti-CTLA4 or other immunotherapeutic agents
• active untreated tuberculosis
• 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

Sponsors & Collaborators

• National Institute for Tuberculosis and Lung Diseases, Poland: lead

Study Sites (1)

Instutut Gruzlicy I Chorob Pluc

Warsaw, Masovian Voivodeship, 01-138, Poland

Location

Related Publications (13)

• Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. doi: 10.1016/S0140-6736(16)32517-X. Epub 2016 Dec 13.

  PMID: 27979383 BACKGROUND

• Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Kelsch C, Lee A, Coleman S, Deng Y, Shen Y, Kowanetz M, Lopez-Chavez A, Sandler A, Reck M; IMpower150 Study Group. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018 Jun 14;378(24):2288-2301. doi: 10.1056/NEJMoa1716948. Epub 2018 Jun 4.

  PMID: 29863955 BACKGROUND

• Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.

  PMID: 26412456 BACKGROUND

• Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.

  PMID: 29658856 BACKGROUND

• Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.

  PMID: 28885881 BACKGROUND

• Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D; ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013 Sep 15;188(6):733-48. doi: 10.1164/rccm.201308-1483ST.

  PMID: 24032382 BACKGROUND

• Suresh K, Voong KR, Shankar B, Forde PM, Ettinger DS, Marrone KA, Kelly RJ, Hann CL, Levy B, Feliciano JL, Brahmer JR, Feller-Kopman D, Lerner AD, Lee H, Yarmus L, D'Alessio F, Hales RK, Lin CT, Psoter KJ, Danoff SK, Naidoo J. Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors. J Thorac Oncol. 2018 Dec;13(12):1930-1939. doi: 10.1016/j.jtho.2018.08.2035. Epub 2018 Sep 26.

  PMID: 30267842 BACKGROUND

• Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, Jordan K; ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv264-iv266. doi: 10.1093/annonc/mdy162. No abstract available.

  PMID: 29917046 BACKGROUND

• Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.

  PMID: 29442540 BACKGROUND

• Delaunay M, Cadranel J, Lusque A, Meyer N, Gounant V, Moro-Sibilot D, Michot JM, Raimbourg J, Girard N, Guisier F, Planchard D, Metivier AC, Tomasini P, Dansin E, Perol M, Campana M, Gautschi O, Fruh M, Fumet JD, Audigier-Valette C, Couraud S, Dalle S, Leccia MT, Jaffro M, Collot S, Prevot G, Milia J, Mazieres J. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. Eur Respir J. 2017 Aug 10;50(2):1700050. doi: 10.1183/13993003.00050-2017. Print 2017 Aug.

  PMID: 28798088 BACKGROUND

• Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, Rosenberg J, Voss MH, Rudin CM, Rizvi H, Hou X, Rodriguez K, Albano M, Gordon RA, Leduc C, Rekhtman N, Harris B, Menzies AM, Guminski AD, Carlino MS, Kong BY, Wolchok JD, Postow MA, Long GV, Hellmann MD. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2017 Mar;35(7):709-717. doi: 10.1200/JCO.2016.68.2005. Epub 2016 Sep 30.

  PMID: 27646942 BACKGROUND

• Cordier JF. Cryptogenic organising pneumonia. Eur Respir J. 2006 Aug;28(2):422-46. doi: 10.1183/09031936.06.00013505.

  PMID: 16880372 BACKGROUND

• Suresh K, Naidoo J, Lin CT, Danoff S. Immune Checkpoint Immunotherapy for Non-Small Cell Lung Cancer: Benefits and Pulmonary Toxicities. Chest. 2018 Dec;154(6):1416-1423. doi: 10.1016/j.chest.2018.08.1048. Epub 2018 Sep 4.

  PMID: 30189190 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Lung Diseases, Interstitial; Pneumonia

Interventions

Prednisone; Clinical Protocols

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Infections

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomization is 1:1 to Arms A and B, it will be conducted using adaptive minimization method. the randomization will be stratified upon three criteria: 1. severity of suspected pneumonitis at baseline (G2 vs. G3-4) 2. response for oncological treatment (PR and CR vs. SD and PD) 3) chronic respiratory system disorders The first patient will be randomized to Arm A or B with simple randomization method using computer program, this part will be oversight by medical monitor. The randomization will be performed for each patient by Primary Investigator.

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 30, 2019
• Study Start: October 1, 2019
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2026
• Last Updated: February 23, 2023

Record last verified: 2023-02

Locations

PL (1)