Durvalumab as Consolidation for Patients LS-SCLC

Phase 2Not Yet RecruitingNCT07055581

Qian Chu100 enrolled

Overview

Small-Cell Lung Cancer (SCLC) accounts for 10% to 15% of new lung cancers and is a highly aggressive neuroendocrine tumor. In the past 30 years, the treatment of SCLC has made very limited progress, and basically made breakthroughs in radiotherapy and chemotherapy. With the advent of the immune era, immunotherapy has achieved initial results in the treatment of SCLC. Approximately one-third of patients with small cell lung cancer are in limited-stage (LS-SCLC) disease at first diagnosis. Except for a very small number of patients with T1-2N0 who can be treated with surgery or stereotactic radiation therapy (SBRT), the standard treatment for the rest of the patients with LS-SCLC is concurrent chemoradiotherapy. The ORR of platinum-combined etoposide regimen combined with thoracic radiotherapy in LS-SCLC can reach 70% to 90%, and the median OS is 16-24 months, which significantly improves the survival of patients. Although many measures have been taken in the treatment of LS-SCLC, only 20% of LS-SCLC can be cured, and most patients have relapse and metastasis after treatment. This study is a single arm phase II preliminary pilot study, aim to assess the efficacy and safety of durvalumab combined with EP prior to CRT and followed by durvalumab consolidation therapy for LS-SCLC.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

100

Conditions

Small Cell Lung Cancer Limited Stage

Interventions

Induction Durvalumab +etoposide/platinum +Radiochemotherapy+ durvalumab maintenanceDRUG

Drug: Durvalumab Induction Phase: Durvalumab (1500mg D1 IV Q3W) combined with EP \[cisplatin or alternatively Carboplatin (AUC 5-6 D1) and Etoposide (100 mg/m² (BSA) D1-3) once every 3 weeks\] for minimum two cycles prior to thoracic radiotherapy Consolidation Phase: Durvalumab (1500 mg once every 4 weeks) until PD or unacceptable toxicities or for a maximum of 24 months, whichever occurs first. Drug: Chemotherapy Concomitant chemoradiotherapy consists of further four cycles Etoposide (100 mg/m² D1-3), cisplatin (75 mg/m² D1) /carboplatin (AUC 5-6 D1) q3w Radiation: Thoracic Radiotherapy Radiotherapy to the primary tumor is recommended to start with the 3rd cycle of EP, which can be delayed appropriately per investigator's decision. 60±6 Gy, 1.8-2 Gy/d or 45±1.5 Gy (1.5 Gy per fraction twice daily, with 4 hours or more between fractions) or other biologically equivalent regimens will be delivered.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 1.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * 2.Histologically or cytologically confirmed small cell lung cancer * 3.Limited-stage, defined as stage I-III SCLC (T any, N any, M0). Patients who are Stage I or II must be medically inoperable as determined by investigator. * 4.Age \> 18 years. * 5.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * 6.Adequate normal organ and marrow function. * 7.Must have a life expectancy of at least 12 week. * 8.At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to enrollment. Exclusion Criteria: * 1.Patients with extensive disease small-cell lung cancer. * 2.Patients who previously received radiotherapy to the thorax or chemotherapy for small cell lung cancer. * 3.Any previous diagnosis of transformed non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) activating mutation positive NSCLC that has transformed to SCLC, or mixed SCLC NSCLC histology. Patients with mixed histology tumors with predominant SCLC histology are allowed. * 4.Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values. * 5.Any concurrent chemotherapy other than study treatment, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. * 6.History of allogenic organ transplantation. * 7.Active or prior documented autoimmune or inflammatory disorders. * 8.Uncontrolled intercurrent illness. * 9.History of leptomeningeal carcinomatosis. * 10.Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) * 11.History of active primary immunodeficiency * 12.Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of antiHBc and absence of HBsAg) and with undetectable HBV DNA (\< 10 IU/ml or under the limit of detection per local lab standard) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * 13.Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. * 14.Prior treatment in a previous durvalumab clinical study. * 15.Known allergy or hypersensitivity to IP or any excipient.

Outcomes

Primary Outcomes

Progression-free survival (PFS)

Defined as the time from first dose of study treatment to date of the first objective disease progression or death from any cause

Time frame: Every 6weeks from the beginning of Cycle 1(each cycle is 42±7days) in induction phase, every 8weeks(each cycle is 56±7days) in first year and every 12weeks in second year in consolidation phase, thereafter every 24weeks until PD or death,up to 3years

Secondary Outcomes

Overall survival (OS)

Defined as the time from first dose of study treatment to date of death from any cause.

Time frame: Up to 3 years after the first patient was enrolled. OS rate at 1 year(%), 2 years(%) and 3 years(%) are presented.

Objective response rate (ORR)

Defined as the percentage of patients with at least 1 assessment result of complete response (CR) or partial response (PR) based on all enrolled patients with evaluable disease per RECIST 1.1.

Time frame: up to 3 years

DoR （Duration of response）

Defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response +1).

Time frame: From the date of first documented response until the first date of documented progression or death in the absence of disease progression ,up to 3 years

Number and proportion of patients with adverse events

AE, SAE, AESI, TRAE, imAE will be recorded by Common Terminology Criteria of Adverse Events version 5 \[CTCAE v.5\],number and proportion of patients will be described.

Time frame: Approximately 3 years