Durvalumab as Consolidation for Patients LS-SCLC

Официальное название

A Phase II Study of Durvalumab Combined With EP Prior to Chemoradiotherapy and Followed by Durvalumab as Consolidation for Patients With Limited-stage Small-cell Lung Cancer (CONCUR Study)

Обзор

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.

Вмешательства

• Препарат Induction Durvalumab +etoposide/platinum +Radiochemotherapy+ durvalumab maintenance
  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/

Первичные конечные точки

• Progression-free survival (PFS) [Срок оценки: 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]

Вторичные конечные точки (4)

• Overall survival (OS) [Срок оценки: 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) [Срок оценки: up to 3 years]
• DoR （Duration of response） [Срок оценки: 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 [Срок оценки: Approximately 3 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital — Чжэнчжоу
• Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT07055581 · ESR-24-22526

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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