A Randomized, Double-Blind, Placebo-Controlled Pilot Study of an Oral, Selective Peripheral Opioid Receptor Antagonist in Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 659
- 主要终点
- Observed Accrual Rate Defined as Rate of Accrual Remaining >= 80% of the Expected
研究概览
简要总结
This randomized pilot clinical trial studies the side effects and best dose of naloxegol and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer. Naloxegol may relieve some of the side effects of opioid pain medication and fight off future growth in the cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine feasibility and safety of long-term administration of two doses of a peripheral opioid receptor antagonist in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line systemic therapy.
SECONDARY OBJECTIVES:
I. To explore whether patients randomized to one or both of the two study drug arms have less decline in health-related quality of life (HRQoL) than patients randomized to placebo.
II. To estimate the difference in the pain levels and opioid/non-opioid analgesic requirements between patients receiving naloxegol or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
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
- •Advanced (stage IIIB or IV) non-small cell lung cancer diagnosed by biopsy of the primary or metastatic site (American Joint Committee on Cancer 7.0)
- •No known presence of known EGFR or EML4-ALK driver mutations in the tumor
- •Started first-line systemic therapy of the investigator's choice within 12 weeks prior to registration, or planning to initiate first-line systemic therapy of the investigator's choice within 4 weeks after registration; no planned initiation of definitive (potentially curative) concurrent chemo-radiation
- •No prior systemic therapy for advanced NSCLC, including chemotherapy, targeted therapy or immunotherapy (other than current treatment); prior palliative radiation permitted; prior adjuvant systemic therapy /radiation is permitted
- •No more than 7 days of prior use of mixed opioid agonist/opioid antagonists or other opioid antagonists within 4 weeks before registration; patients should not receive such medications after registration and for the entire duration of study treatment
- •No methadone within 4 weeks prior to registration
- •Patients must have used opioid medication(s) for pain at some time in the 4 weeks prior to registration; current use of opioids (at the time of registration) and/or later during the course of the study is permitted but not required
- •Expected survival > 3 months
- •No concurrently active second invasive malignancies except non-melanoma skin cancer
- •No history of gastrointestinal obstruction, or conditions that increase the risk of gastrointestinal obstruction, perforation, bleeding or impairment of the gastrointestinal wall; no abdominal surgery within 60 days of registration
- •No acute gastrointestinal conditions, such as: obstruction, fecal impaction, obstipation, acute surgical abdomen, ongoing need for manual maneuvers to induce bowel movements (such as digital evacuation)
- •No conditions that may compromise blood-brain barrier permeability (e.g., multiple sclerosis, recent brain trauma, Alzheimer's disease, or uncontrolled seizures)
- •No symptomatic and untreated brain metastases; patients will be eligible for study if radiation therapy for brain metastases was completed at least 7 days prior to registration
- •Patients having received stereotactic radiation will be eligible if the radiation was completed at least 7 days prior to registration
- •Patients having undergone surgical resection of brain metastases will be eligible after they have healed and recovered from the surgical intervention sufficiently to start systemic treatment for NSCLC, as determined by a neurosurgeon
- •No known leptomeningeal carcinomatosis
- •No history of myocardial infarction =< 6 months prior to registration; no current symptomatic congestive heart failure, uncontrolled angina, or uncontrolled cardiac arrhythmias
- •No severe hepatic impairment (Child-Pugh class C) or acute liver disease
- •No known serious or severe hypersensitivity reaction to naloxegol or any of its excipients
- •No concurrent use of moderate/strong CYP3A4 inhibitors, or strong CYP3A4 inducers
- •Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown; therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required; a female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Calculated (calc.) creatinine clearance >= 60 mL/min calculated using the Cockcroft-Gault formula
- •Total bilirubin =< 1.2 x upper limit of normal (ULN) unless due to Gilbert's disease
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
排除标准
- 未提供
研究组 & 干预措施
Group I (lower dose naloxegol, placebo)
Patients receive lower dose naloxegol PO QD and placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Naloxegol (Drug)
Group I (lower dose naloxegol, placebo)
Patients receive lower dose naloxegol PO QD and placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Placebo (Other)
Group I (lower dose naloxegol, placebo)
Patients receive lower dose naloxegol PO QD and placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Group I (lower dose naloxegol, placebo)
Patients receive lower dose naloxegol PO QD and placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Group II (placebo, higher dose naloxegol)
Patients receive placebo PO QD and higher dose naloxegol PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Naloxegol (Drug)
Group II (placebo, higher dose naloxegol)
Patients receive placebo PO QD and higher dose naloxegol PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Placebo (Other)
Group II (placebo, higher dose naloxegol)
Patients receive placebo PO QD and higher dose naloxegol PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Group II (placebo, higher dose naloxegol)
Patients receive placebo PO QD and higher dose naloxegol PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Group III (placebo)
Patients receive placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Placebo (Other)
Group III (placebo)
Patients receive placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Group III (placebo)
Patients receive placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Observed Accrual Rate Defined as Rate of Accrual Remaining >= 80% of the Expected
时间窗: Up to 2 years
Calculated as the total number of patients accrued to the study over two years divided by 184, the total expected accrual of patients evaluable for the primary endpoint.
Proportion of Patients Alive Who Continue Study Drug and Complete the Health-related Quality of Life and Other Forms
时间窗: Up to 6 months
The proportion of patients alive at 6 months who continue study drug and complete the health-related quality of life and other forms for at least 6 months will be calculated by arm.
Incidence of Adverse Events as Described and Graded by the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0
时间窗: Up to 2 years
The frequency of adverse events will be summarized by arm and compared between each treatment arm vs the placebo arm using Fisher's exact test. \<3 is better and 3+ is worse.
次要结局
- Change in Trial Outcome Index(Baseline to 6 months)
- Change in Function Subscales(Baseline to 6 months)
- Change in Lung Cancer Subscale of the Functional Assessment of Cancer Therapy-Lung(Baseline to 6 months)
- Patient-reported Outcome Assessed by Patient-Reported Outcome-Common Terminology Criteria for Adverse Events(Up to 2 years)
- Patient-reported Outcome Assessed by a Urinary Retention Linear Analogue Self-Assessment(Baseline to 6 months)
- Opioid-induced Constipation Rating Scale(Baseline to 6 months)
- Level of Pain(Baseline to 6 months)
- Analgesic Use(Up to 2 years)
- Unexpected Clinical Outcomes With Chemotherapy(Up to 2 years)
- Progression-free Survival Assessed by Using the Standard Response Evaluation Criteria in Solid Tumors 1.1 Criteria(From randomization to disease progression/relapse, death, or loss to follow-up, whichever occurs first, assessed up to 2 years)
- Overall Survival(From randomization to death or loss to follow-up, whichever occurs first, assessed up to 2 years)