Niraparib Added to Anti-PD-L1 Antibody Maintenance in SLFN11-positive, Extensive-disease SCLC

Официальное название

A Single-arm Phase II Trial of the Addition of Niraparib to Anti-PD-L1 Antibody Maintenance in Patients With SLFN11-positive, Extensive-disease Small Cell Lung Cancer.

Обзор

RAISE is an international, multicentre, single-arm phase II trial. The trial treatment consists of the addition of niraparib, 200 mg orally once daily to anti-PD-L1 antibody maintenance. The primary objective of this trial is to assess the clinical efficacy of the addition of niraparib to anti-PD-L1 monoclonal antibody maintenance treatment in patients with SLFN11-positive ED-SCLC which has not progressed following standard first-line chemo-immunotherapy.

Вмешательства

• Препарат Niraparib
  200 mg orally once daily, until PD 300 mg once daily if body weight ≥77 kg and platelets ≥150 g/L, until PD

Первичные конечные точки

• Progression-free survival (PFS) rate at 3 months by investigator assessment (according to RECIST v1.1) [Срок оценки: From date of enrolment until 3 months post-enrolment]

Вторичные конечные точки (4)

• Progression-free survival (PFS) [Срок оценки: From the date of enrolment until last tumour assessment (approximately 25-30 months after the enrolment of the first patient)]
• Overall survival (OS) [Срок оценки: From the date of enrolment until death from any cause (approximately 25-30 months after the enrolment of the first patient)]
• Disease control rate (DCR) by investigator assessment (according to RECIST v1.1) [Срок оценки: approximately 25-30 months after the enrolment of the first patient]
• Adverse events according to CTCAE v5.0 [Срок оценки: From the date of enrolment until last patient last visit (approximately 25- 30 months after enrolment of the first patient)]

Критерии участия

Критерии включения

Inclusion criteria for SLFN11-expression testing

• Written IC part 1: for SLFN11-screening must be signed and dated by the patient and the investigator prior to sending any tumour material to the central laboratory.
• Histologically or cytologically confirmed ED-SCLC (stage IV according to the 8th TNM classification).
• Availability of FFPE tumour tissue for screening.

Inclusion criteria for trial participation

• Written IC part 2: for trial participation must be signed and dated by the patient and the investigator prior to any trial-related intervention.
• High SLFN11-expression on FFPE tumour material:

SLFN11-expression is determined at the central screening laboratory in Basel. Overexpression is defined as detectable protein expression by IHC in ≥20% of tumour cells.

• Patients must have received standard first-line chemo-immunotherapy, consisting of 4 cycles of platinum-etoposide chemotherapy in combination with an anti-PD-L1 antibody (atezolizumab or durvalumab). Patients who started the immunotherapy at chemotherapy cycle 2 are eligible.
• ED-SCLC must not have progressed during or after standard chemo-immunotherapy (as per RECIST v1.1).
• Patients must be candidates for ongoing maintenance treatment with immune-checkpoint inhibition.
• Adequate haematological function:
• Adequate renal function:
• Adequate liver function:
• ECOG PS 0-2
• Age ≥18 years
• Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 4 weeks before enrolment and within 3 days before treatment start.

Критерии исключения

• Symptomatic brain metastases
• Any clinically active cancer, other than SCLC Exception: malignancies with negligible risk of metastases or death (e.g. 5-year OS rate of >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or stage I uterine cancer. Hormonal therapy for non-metastatic prostate or ductal carcinoma in situ is allowed.

Consolidating thoracic radiotherapy. Palliative radiotherapy to the brain or to bones is allowed.

• History of idiopathic pulmonary fibrosis, organising pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Any lung disease requiring systemic steroids in doses of >10 mg prednisolone (or equivalent dose of other steroid).
• Any serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) which in the opinion of the investigator would compromise the patient's ability to complete the trial or interfere with the evaluation of the efficacy and safety of the protocol treatment.
• Inadequately controlled hypertension, defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >95 mmHg.

The patient must be considered stable and hypertension medically controlled.

• History of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).
• Prior Reversible Encephalopathy Syndrome (PRES)
• Severe renal or hepatic impairment.
• Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
• Treated with live vaccine within 30 days before enrolment.
• Hypersensitivity to niraparib or any of its excipients (e.g., tartrazine).
• Women who are pregnant or in the period of lactation.
• Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial and within the required timelines after last dose of niraparib treatment.
• Judgment by the investigator that the patient is unlikely to comply with trial procedures, restrictions and requirements.

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

Швейцария · 7 центров

• Kantonsspital Baden — Baden
• University Hospital Basel — Basel
• Inselspital Bern — Bern
• Kantonsspital St. Gallen — Sankt Gallen
• Centre Hospitalier du Valais Romand — Sion
• Bürgerspital Solothurn — Solothurn
• Kantonsspital Winterthur — Winterthur

Франция · 4 центра

• CHU - Angers — Angers
• Centre Hospitalier d'Avignon — Avignon
• Caen - CHU — Caen
• Lyon - Centre Léon Bérard — Lyon

Италия · 3 центра

• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) — Meldola
• Instituto Europeo di Oncologia (IEO) — Milan
• Santa Maria della Misericordia Hospital — Perugia

Испания · 3 центра

• Complejo Hospitalario Universitario a Coruña — A Coruña
• Complejo Hospitalario de Jaén — Jaén
• Hospital Universitario Puerta de Hierro — Madrid

Германия · 1 центр

• LMU Klinikum / Thoracic Oncology center Münich — München

Идентификаторы

NCT: NCT05718323 · ETOP 23-22

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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