Consolidation Sintilimab After Concurrent Chemoradiation in Patients With Unresectable Stage III NSCLC

NCT03884192 | Unknown Phase 3 DMC

• 1 other identifier: CONSIST
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, multi-center, randomized, control phase III trial, to compare the efficacy and safety of consolidation therapy with sintilimab (IBI308) versus best supported care (BSC), in unresectable stage III NSCLC patients who do not experience disease progression after initial concurrent chemoradiation.

Conditions

Carcinoma, Non-Small Cell Lung

Keywords

Locally advanced; Stage III Non-Small Cell Lung Cancer; Unresectable Non-Small Cell Lung Cancer; Concurrent Chemoradiation; Immune-mediated cancer therapy; PD-1; Sintilimab; IBI308

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS (per RECIST 1.1 as assessed by the investigator) will be defined as the time from the date of randomisation until the date of objective disease progression or death (by any cause in the absence of progression).

  up to 24 months after enrollment or study close

Secondary Outcomes (6)

• Overall survival (OS)

  up to 24 months after enrollment or study close

• Objective Response Rate (ORR)

  up to 24 months after enrollment or study close

• Disease Control Rate (DCR)

  up to 24 months after enrollment or study close

• Duration of Response (DoR)

  up to 24 months after enrollment or study close

• Progression Free Survival (PFS) Rate at 12/18 months

  From the date of randomization until the Kaplan-Meier estimate of PFS at 12/18months

Study Arms (2)

Sintilimab Arm

EXPERIMENTAL

Sintilimab consolidation therapy

Drug: Consolidation Sintilimab

Observation Arm

NO INTERVENTION

Observation

Interventions

Consolidation Sintilimab DRUG

Sintilimab consolidation therapy after concurrent chemoradiation, 200mg IV, every 3 weeks, until progressive disease (PD, unless patients can continuously benefit from study treatment per investigators' judgement), start new anti-cancer therapy, intolerable toxicity, withdraw informed consent or other conditions that require study treatment discontinuation. Sintilimab will be given at a maximum of 12 months.

Sintilimab Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent before initiation of any study procedures
• Age ≥ 18 years and ≤ 75 years
• Histologically or cytologically confirmed NSCLC, with unresectable local advanced disease (stage III according to NSCLC staging version 8)
• Expected survival over 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• At least 1 measurable disease according to RECIST 1.1
• Pulmonary function: forced expiratory volume at one second (FEV1) \> 1 liter(L)
• For all female patients of childbearing potential, a negative pregnancy test (either urine or serum) must be obtained within 3 days before the first dose (Cycle 1, Day 1) of study treatment. If a urine pregnancy test shows an unconfirmed result, a serum pregnancy test must be performed.
• Adequate hematopoietic function, defined as: absolute neutrophil count (ANC) ≥ 1.5 x 10\*9/L; platelet count ≥100 x 10\*9/L; hemoglobin ≥90 g/L \[no blood transfusion within 7 days or not erythropoietin (EPO) dependent\]
• Adequate liver function, defined as: total serum bilirubin ≤ 1.5 x upper limit of normal (ULN); serum alanine transaminase (ALT) and aspartic transaminase (AST) ≤ 2.5 x ULN, with no liver transplantation
• Adequate renal function, defined as: serum creatinine ≤ 1.5 x ULN or calculated creatinine-clearance ≥ 60 ml/min (Cockcroft-Gault). Urine protein less than 2+ by urinalysis or 24-hour urinary protein quantity \< 1g
• Adequate coagulation function, defined as: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN. For patients receiving anticoagulant therapy can be enrolled if PT is within the range defined by anticoagulant therapy.
• Myocardial enzymes are within normal range
• All subjects of childbearing potential must agree to use efficient contraceptive methods that result in a failure rate of \< 1% per year during the study treatment period and for at least 180 days after discontinuation from study treatment.

You may not qualify if:

• Being treated by other investigational drugs within an interventional study, or have received any investigational drugs or instruments within 4 weeks prior to the first dose of study treatment
• Being enrolled in other interventional studies, unless they are observational studies or during the follow-up stage of an interventional study
• NSCLC histology with small cell lung cancer (SCLC) components
• Active or autoimmune disease history (within the past 2 years), or history of immune deficiency
• Previous immune therapy including: anti PD-1, anti PD-L1, anti PD-L2 or treatment targeting other co-stimulatory or co-inhibitory T-cell receptors \[e.g. cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, and CD137\]
• a) Systemic therapy with Chinese patent medicine or drugs of immunoregulation effect (including thymosin, interferon, interleukin, unless local delivery for controlling pleural effusion) within 2 weeks prior to the first dose of study treatment, or major surgery within 4 weeks prior to the first dose of study treatment
• Clinical evidence of active diverticulitis, abdominal abscess, or gastrointestinal obstruction
• Previous organ or blood system transplantation
• Known allergic to pemetrexed, paclitaxel, etoposide, cisplatin, carboplatin, sintilimab component and/or any excipients
• A history of active autoimmune disease requiring systemic treatment (e.g. using drugs for disease remission, corticosteroids or immunosuppressor) within 2 years prior to the first dose of study treatment. Substitution therapy (e.g. thyroxine, insulin or physiological corticosteroids for treating adrenal or pituitary dysfunction) is not considered as a systemic treatment.
• a) Diagnosis as immunodeficiency, or being treated with systemic glucocorticoid or other kinds of immunosuppressor within 7 days prior to the first dose of study treatment. A physiological dose of glucocorticoid (≤10 mg/day prednisone or equivalent dose of other steroids) is permitted.
• Previously diagnosis as other malignant tumors within 5 years prior to the first dose of study treatment, with the exception of: skin basal cell carcinoma or squamous cell carcinoma with radical treatment, and/or carcinoma in situ underwent radical resection
• History of non-infectious pneumonitis requiring treatment with glucocorticoid within 1 year prior to the first dose of study treatment, or currently existed interstitial lung disease
• Active infectious that required systemic therapy
• Know psychiatric illness or drug abuse that would limit compliance with study requirements

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital

Jinan, Shandong, China

RECRUITING

Related Publications (7)

• Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):2181-90. doi: 10.1200/JCO.2009.26.2543. Epub 2010 Mar 29.

  PMID: 20351327 BACKGROUND

• Yoon SM, Shaikh T, Hallman M. Therapeutic management options for stage III non-small cell lung cancer. World J Clin Oncol. 2017 Feb 10;8(1):1-20. doi: 10.5306/wjco.v8.i1.1.

  PMID: 28246582 BACKGROUND

• Ahn JS, Ahn YC, Kim JH, Lee CG, Cho EK, Lee KC, Chen M, Kim DW, Kim HK, Min YJ, Kang JH, Choi JH, Kim SW, Zhu G, Wu YL, Kim SR, Lee KH, Song HS, Choi YL, Sun JM, Jung SH, Ahn MJ, Park K. Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non-Small-Cell Lung Cancer: KCSG-LU05-04. J Clin Oncol. 2015 Aug 20;33(24):2660-6. doi: 10.1200/JCO.2014.60.0130. Epub 2015 Jul 6.

  PMID: 26150444 BACKGROUND

• Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, D'Amico TA, DeCamp MM, Dilling TJ, Dobelbower M, Doebele RC, Govindan R, Gubens MA, Hennon M, Horn L, Komaki R, Lackner RP, Lanuti M, Leal TA, Leisch LJ, Lilenbaum R, Lin J, Loo BW Jr, Martins R, Otterson GA, Reckamp K, Riely GJ, Schild SE, Shapiro TA, Stevenson J, Swanson SJ, Tauer K, Yang SC, Gregory K, Hughes M. Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017 Apr;15(4):504-535. doi: 10.6004/jnccn.2017.0050.

  PMID: 28404761 BACKGROUND

• Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. doi: 10.1016/S1470-2045(14)71207-0. Epub 2015 Jan 16.

  PMID: 25601342 BACKGROUND

• Tsujino K, Kurata T, Yamamoto S, Kawaguchi T, Kubo A, Isa S, Hasegawa Y, Ou SH, Takada M, Ando M. Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? A pooled analysis of the literature. J Thorac Oncol. 2013 Sep;8(9):1181-9. doi: 10.1097/JTO.0b013e3182988348.

  PMID: 23883782 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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President of Shandong Cancer Hospital and Institute

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: March 21, 2019
• Study Start: December 12, 2018
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2021
• Last Updated: March 21, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)