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

Sponsor

Shandong Cancer Hospital and Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT03884192

Collaborator

(none)

162

Enrollment

Location

Arms

36.6

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small Cell Lung	Drug: Consolidation Sintilimab	Phase 3

Detailed Description

This is an open label, multi-center, randomized, control study of sintilimab versus BSC in unresectable local advanced stage III NSCLC patients without disease progression after concurrent chemoradiation.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

162 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CONSIST: A Phase III Randomized Control Study of Consolidation Sintilimab (IBI308) After Concurrent Chemoradiation Versus Chemoradiation Alone in Patients With Unresectable Local Advanced Stage III NSCLC

Actual Study Start Date :

Dec 12, 2018

Anticipated Primary Completion Date :

Dec 30, 2020

Anticipated Study Completion Date :

Dec 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sintilimab Arm Sintilimab consolidation therapy	Drug: Consolidation Sintilimab 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.
No Intervention: Observation Arm Observation

Arm

Intervention/Treatment

Experimental: Sintilimab Arm

Sintilimab consolidation therapy

Drug: Consolidation Sintilimab

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.

No Intervention: Observation Arm

Observation

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [up to 24 months after enrollment or study close]
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).

Secondary Outcome Measures

Overall survival (OS) [up to 24 months after enrollment or study close]
OS (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date of randomisation until death due to any cause.
Objective Response Rate (ORR) [up to 24 months after enrollment or study close]
ORR (per RECIST 1.1 as assessed by the investigator) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).
Disease Control Rate (DCR) [up to 24 months after enrollment or study close]
DCR (per RECIST 1.1 as assessed by the investigator) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR), or stable disease (SD).
Duration of Response (DoR) [up to 24 months after enrollment or study close]
DoR (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) until the date for the first documented response of progressive disease (PD) or death in the absence of progression.
Progression Free Survival (PFS) Rate at 12/18 months [From the date of randomization until the Kaplan-Meier estimate of PFS at 12/18months]
PFS rate at 12/18 months is defined as the proportion (%) of patients who are alive and progression free at 12 and 18months from the date of randomisation.
Treatment-related Adverse Events (AEs) [From the date of randomization to 90 days after last dose of study treatment]
The grade of AEs and the number of patients with AEs are assessed by the investigator based on CTCAE v4.03 from the date of randomization to 90 days after last dose of study treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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)
Patient must not have received any anti-cancer therapy for the purpose of treating lung cancer. However, exploratory thoracotomy, mediastinoscopy, excision biopsy, and other kinds of surgery for diagnosis and staging purpose is acceptable. Patients with local or regional recurrent disease after pneumonectomy is allowed to participate if they meet other inclusion criteria (e.g. stage III, inappropriate for re-operation).
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 109/L; platelet count ≥100 x 109/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.

Exclusion Criteria:

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]

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.

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
Know human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive)
Untreated active viral hepatitis B (HBV)

Patients with HBV who meet the following criteria are also eligible:

HBV virus load (VL) <1000 copy/ml (200 IU/ml), and patients must continuously receive anti-HBV therapy during all through study treatment phase to prevent virus activation
Patients with a result of anti-HBc(+)、HBsAg (-)、anti-HBs (-) 和 HBV VL (-) are not required to receive prophylactic anti-HBV therapy, but must be closely monitored for virus re-activation
Patients with active HCV infection (HCV antibody positive and HCV-RNA > the lower detection limit)
History or evidence of disease, treatment or laboratory abnormalities that would interfere the study outcome, prevent patients from participating entirely, or ineligible to enroll per the investigators' judgement
Pregnant or lactating women