COordinated Nivolumab and IntraperiToneal IL-2 for Gastric CanceR With PeritOneaL Metastasis (CONTROL) Phase 1b Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Mayo Clinic
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Change of reduction in the peritoneal carcinomatosis index
研究概览
简要总结
This phase Ib trial test effects of aldesleukin in combination with nivolumab and standard chemotherapy in treating patients with gastric cancer that has spread to the tissue lining of the abdomen (peritoneal metastasis). Aldesleukin is similar to a protein that naturally exists in the body that stimulates the immune system to fight infections. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving aldesleukin in combination with nivolumab and standard chemotherapy may work better in treating patients with gastric cancer with peritoneal metastasis.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the reduction in the peritoneal carcinomatosis index (PCI) after completion of the study treatment.
SECONDARY OBJECTIVES:
I. Evaluate histological response of the peritoneal metastasis to study treatment using the peritoneal regression grading score (PRGS).
II. Assess overall survival (OS). III. Assess progression-free survival (PFS). IV. Assess safety and tolerability of the study regimen.
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
- •PRE-REGISTRATION: Age >= 18 years
- •PRE-REGISTRATION: Disease characteristics
- •Histological confirmation of adenocarcinoma of the stomach or gastroesophageal junction (GEJ)
- •Currently receiving first-line therapy with leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) and nivolumab without evidence of disease progression OR planning to start first-line therapy with FOLFOX and nivolumab
- •PRE-REGISTRATION: No radiographic or histological evidence of non-peritoneal metastasis
- •PRE-REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •PRE-REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
- •PRE-REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research
- •PRE-REGISTRATION: Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
- •REGISTRATION: Peritoneal Carcinomatosis Index (PCI) >= 1 and =< 24 obtained =< 30 days prior to registration
- •REGISTRATION: Clinical, pathological, or radiographic evidence of peritoneal metastasis per PCI and Peritoneal Regression Grading Score (PRGS)
- •REGISTRATION: Hemoglobin >= 8.0 g/dL (obtained =< 30 days prior to registration)
- •REGISTRATION: Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 30 days prior to registration)
- •REGISTRATION: Platelet count >= 75,000/mm^3 (obtained =< 30 days prior to registration)
- •REGISTRATION: Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 30 days prior to registration)
- •REGISTRATION: Alanine aminotransferase (ALT) AND aspartate transaminase (AST) =< 1.5 x ULN (obtained =< 30 days prior to registration)
- •REGISTRATION: Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy, then PT/INR is within target range of therapy (obtained =< 30 days prior to registration)
- •REGISTRATION: Calculated creatinine clearance >= 40 ml/min using the Cockcroft-Gault formula (obtained =< 30 days prior to registration)
- •REGISTRATION: Negative pregnancy test done =< 8 days prior to registration, for persons of childbearing potential only
- •REGISTRATION: Provide written informed consent
- •REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
- •REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research
- •REGISTRATION: Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
排除标准
- •PRE-REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
- •PRE-REGISTRATION: Any of the following prior therapies: IL-2 or chronic corticosteroids, or immunosuppressive agents
- •NOTE: Inhaled corticosteroids are allowed
- •PRE-REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •PRE-REGISTRATION: Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
- •PRE-REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Or psychiatric illness/social situations that would limit compliance with study requirements
- •Autoimmune disease
- •PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •PRE-REGISTRATION: Active second malignancy currently receiving systemic treatment =< 6 months prior to pre-registration
- •PRE-REGISTRATION: History of myocardial infarction =< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •REGISTRATION: Identification of non-peritoneal metastasis during laparoscopy
- •REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
- •REGISTRATION: Any of the following therapies: prior immune checkpoint inhibitors, prior IL-2, or chronic corticosteroids or immunosuppressive agents
- •NOTE: Inhaled corticosteroids are allowed. One-time antiemetic dose is allowed
- •REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •REGISTRATION: Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy
- •REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Or psychiatric illness/social situations (e.g., substance abuse) that would limit compliance with study requirements
- •Autoimmune disease requiring systemic treatment
- •Small bowel obstruction
- •REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •REGISTRATION: History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •REGISTRATION: Small bowel obstruction < 15 days prior to registration
研究组 & 干预措施
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Computed Tomography (Procedure)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Diagnostic Laparoscopy (Procedure)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Positron Emission Tomography (Procedure)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Biopsy Procedure (Procedure)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Fluorouracil (Drug)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Nivolumab (Biological)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Oxaliplatin (Drug)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Aldesleukin (Biological)
Treatment (aldesleukin, nivolumab, chemotherapy)
Patients receive aldesleukin IP over at least 40 minutes on days 1 and 8 of each cycle. Patients also receive standard of care nivolumab IV over 30 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-3 for each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo diagnostic laparoscopy with biopsy, PET/CT or PET/MRI, and collection of blood and tissue samples throughout the trial.
干预措施: Leucovorin Calcium (Drug)
结局指标
主要结局
Change of reduction in the peritoneal carcinomatosis index
时间窗: About 90 days after last dose of aldesleukin (IL-2)
Incidence of adverse events
时间窗: About 90 days after last dose of aldesleukin (IL-2)
次要结局
- Progression free survival(From study entry to the first of either disease progression or death, assessed up to 3 years)
- Overall survival(From date of study entry to date of death or last follow up, assessed up to 3 years)
- Histological response of the peritoneal metastasis(About 90 days after last dose of aldesleukin (IL-2))