NCT06663098招募中2 期
Continued PD-L1 Inhibition With Atezolizumab With Rechallenge Chemotherapy in Patients With Sensitive Relapse SCLC Progressing on First-line Platinum-etoposide Chemotherapy and a PD-L1 Inhibitor: CARRY-ON Study-GOIRC-01-2023
Gruppo Oncologico Italiano di Ricerca Clinica25 个研究点 分布在 1 个国家目标入组 142 人开始时间: 2025年1月24日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 142
- 试验地点
- 25
- 主要终点
- overall survival
研究概览
简要总结
The goal of this clinical trial is to learn if a combination of atezolizumab and standard chemotherapy works to treat sensitive Extensive-stage Small Cell Lung Cancer, progressing after first-line of treatment.
The main questions it aims to answer are:
- Does combination of atezolizumab and standard chemotherapy increase overall survival?
- What medical problems do participants have when taking combination of atezolizumab and standard chemotherapy?
Participants will:
- take atezolizumab and standard chemotherapy every 3 weeks for 4 cycles and than atezolizumab every 3 weeks up to 18 cycles.
- visit the clinic once every 3 weeks for checkups and tests
- perform Radiological assessments after 6 weeks and then every 12 weeks to determine response to treatment.
详细描述
The CARRY-ON study is a multicenter, prospective, open-label single-arm phase II trial, designed to seek for a signal of efficacy of continuing PD-L1 inhibition in patients with sensitive relapse ES-SCLC by adding atezolizumab to rechallenge carboplatin-etoposide chemotherapy. The trial is planned to enroll 142 patients with sensitive relapse ES-SCLC from 25 Italian centers. Sensitive relapse is defined as SCLC relapsed or progressed to first-line chemo-immunotherapy with PD-L1 inhibition (with either atezolizumab or durvalumab) at least 60 days after the last chemotherapy administration. Eligible patients will receive re-challenge chemotherapy (either carboplatin AUC 4 on day 1 plus etoposide 80 mg/m2 days 1-3 or carboplatin AUC 5 on day 1 plus etoposide 100 mg/m2 days 1-3, at investigator's choice) plus atezolizumab 1200 mg flat dosing on day 1 every 3 weeks until PD, unacceptable toxicity or to a maximum of 4 cycles (induction phase) followed by atezolizumab 1200 mg flat dosing every 3 weeks (maintenance phase) until completion of 1 year of maintenance (up to 18 cycles), progressive disease, unacceptable toxicity, patient refusal or loss of clinical benefit (investigator's choice), whichever occur first.
Subjects will attend clinical visits at regular intervals to receive trial treatment and for efficacy and safety assessments. All subjects will be monitored continuously for any AE while on study treatment.
Radiological assessment will be performed by computed tomography (CT) scan at week 6 (± 7 days), at week 12 (± 7 days) and every 12 weeks (± 7 days) thereafter.
The duration of the study is expected to be a maximum of 45 months. The study recruitment period is expected to be approximately 24 months, maximum treatment duration will be 15 months (3 months of induction and 12 months of maintenance), and subsequent survival follow-up will be a maximum of 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of small-cell lung cancer (SCLC) (according to WHO classification 2015) confirmed at pathology (histology or cytology).
- •Male or female and ≥ 18 years of age.
- •Life expectancy ≥ 12 weeks.
- •Disease progression at least 60 days after the completion of first-line chemotherapy consisting of at least 4 cycles of platinum-etoposide plus either atezolizumab or durvalumab and have not received any other treatment (except for immunotherapy as maintenance treatment); the 60 day-interval is calculated from the date of the last chemotherapy administration to the date of the first radiologically documented progressive disease.
- •No previous radiotherapy on the only one site disease progression, unless that site had subsequent evidence of progressive disease.
- •Eastern Cooperative Oncology Group performance status (ECOG PS) ≤
- •Patients with treated brain metastases (or untreated but asymptomatic) and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from AEs related to radiotherapy to < grade 1 (except alopecia)
- •For Females: must be postmenopausal (defined as occurring 12 months after last menstrual period) before the screening visit, or are surgically sterile. If they are of childbearing potential, a negative serum pregnancy test prior to study entry has to be documented; furthermore, they agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 5 months after the last dose of study drug,or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject.
- •For Males: even if surgically sterilized (i.e., post-vasectomy status) agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject.
- •Normal baseline laboratory values as specified below:
- •Absolute neutrophil count (ANC) ≥1500/mm3
- •Platelet count ≥ 100 x 109/L (≥100,000/μL) without transfusion
- •Hemoglobin ≥ 90 g/L (≥ 9 g/dL); patients may be transfused to meet this criterion.
- •Total bilirubin < 1.5x the institutional upper limit of normal (ULN)
- •Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5x the institutional ULN (< 5x if liver function test elevations are due to liver metastases)
- •Creatinine < 1.5x institutional ULN or estimated creatinine clearance using the Cockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levels above institutional limits
- •For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 x ULN
- •Negative HIV test at screening {with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable viral load}
- •Negative hepatitis B surface antigen (HBsAg) test at screening
- •Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following:
- •Negative total hepatitis B core antibody (HBcAb)
- •Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA testNegative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test must be performed for patients who have a positive HCV antibody test.
- •Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria.
- •Recovered (i.e., ≤ grade 1 toxicity) from effects of prior anticancer therapy, except alopecia.
- •Prior radiotherapy is allowed provided that it has been completed more than 2 weeks before starting protocol treatment and patients have recovered from AEs related to radiotherapy to < grade 1
- •Ability to comply with protocol requirements.
- •The patient or the patient's legal representative has to be able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
排除标准
- •More than 1 line of prior treatment for ES-SCLC.
- •First-line treatment without either atezolizumab or durvalumab.
- •First-line chemotherapy other than platinum-etoposide.
- •Less than 4 cycles of first-line platinum-etoposide.
- •Presence of resistant relapse (progressive disease within 60 days from the end of first-line chemotherapy) or refractory disease (progressive disease during the first 4 cycles of first-line chemoimmunotherapy).
- •Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to randomization)requiring immediate radiotherapy for palliation. Patients with treated brain metastases (or untreated but asymptomatic) and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible provided that all of the following criteria are met:
- •If treated, at least 14 days between the end of stereotactic radiotherapy or whole brain radiotherapy and initiation of study treatment and recovery from AEs related to radiotherapy to ≤ grade 1 (except alopecia), or at least 28 days between neurosurgical resection and initiation of study treatment;
- •Anticonvulsant therapy at a stable dose is permitted;
- •Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord);
- •There is no evidence of interim intracranial progression between completion of CNS directed therapy (if administered) and initiation of study treatment.
- •Evidence of leptomeningeal disease.
- •Any comorbid condition or unresolved toxicity that would preclude administration of second-line chemotherapy.
- •Patient has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines and COVID vaccines that do not contain live virus are permitted. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment except for PD-L1 inhibitor maintenance as part of first-line treatment.
- •Any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of registration . The following are exceptions to this criterion:
- •Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);
- •Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent;
- •Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- •Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present.
- •Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than those in the present study. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- •Treatment with any other investigational agent within 30 days prior to starting study treatment, or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- •Infection requiring intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
- •Prior allogeneic stem cell or solid organ transplantation.
- •For female subjects: positive serum pregnancy test, pregnancy, or breastfeeding.
- •Surgery within 4 weeks (or 2 weeks for a minor surgery) before study enrolment and not fully recovered to baseline or to a stable clinical status. Insertion of a vascular device is allowed.
- •Patients who experienced medically significant or NCI CTCAE Grade 3 or higher toxicities in response to first-line immunotherapy
- •Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.
研究组 & 干预措施
Arm 1
Experimental
re-challenge chemotherapy plus atezolizumab 1200 mg flat dosing
干预措施: Etoposide (Drug)
Arm 1
Experimental
re-challenge chemotherapy plus atezolizumab 1200 mg flat dosing
干预措施: Atezolizumab (Drug)
Arm 1
Experimental
re-challenge chemotherapy plus atezolizumab 1200 mg flat dosing
干预措施: Carboplatin (Drug)
结局指标
主要结局
overall survival
时间窗: through study completion, an average of 1 year
overall survival (OS), defined as the time from the date of registration to the date of death from any cause. Patients still alive at the time of analysis are censored at the last time they are known to be alive.
次要结局
- frequency of adverse events(30 days post last dose of study drug)
- Progression Free Survival(through study completion, an average of 6 months)
- Objective response rate(through study completion, an average of 1 year)
研究者
研究点 (25)
Loading locations...
相似试验
招募中
1 期
Integration of the PD-L1 Inhibitor Atezolizumab and WT1/DC Vaccination Into Platinum/Pemetrexed-based First-line Treatment for Epithelioid Malignant Pleural MesotheliomaMalignant Pleural MesotheliomaNCT05765084University Hospital, Antwerp15
Unknown
2 期
Combined Atezolizumab and Chemotherapy (Carboplatin Plus Etoposide) in Neoadjuvant Treating Limited-Stage Small Cell Lung Cancer PatientsSmall-cell Lung CancerNeoadjuvant TherapyNCT04696939Shanghai Pulmonary Hospital, Shanghai, China100
进行中（未招募）
2 期
Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part SarcomaMetastatic Alveolar Soft Part SarcomaUnresectable Alveolar Soft Part SarcomaNCT03141684National Cancer Institute (NCI)63
已完成
2 期
A Phase II Study of Atezolizumab in Combination With Bevacizumab, Carboplatin or Cisplatin, and Pemetrexed for EGFR-mutant Metastatic Non-small Cell Lung Cancer Patients After Failure of EGFR Tyrosine Kinase Inhibitors.NSCLC Stage IIIB~IVNCT04147351National Taiwan University Hospital22
进行中（未招募）
2 期
Atezolizumab With Chemotherapy in Treating Patients With Anaplastic or Poorly Differentiated Thyroid CancerMetastatic Thyroid Gland CarcinomaPoorly Differentiated Thyroid Gland CarcinomaStage IVA Thyroid Gland Anaplastic Carcinoma AJCC v8Stage IVB Thyroid Gland Anaplastic Carcinoma AJCC v8Stage IVC Thyroid Gland Anaplastic Carcinoma AJCC v8Thyroid Gland Anaplastic CarcinomaUnresectable Thyroid Gland CarcinomaNCT03181100M.D. Anderson Cancer Center50