POSITION: A Pilot Study of Induction PARP Inhibition in Ovarian Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 6
- 主要终点
- Change in deoxyribonucleic acid (DNA) copy number
研究概览
简要总结
This pilot early phase I trial studies talazoparib to determine if certain characteristics of the deoxyribonucleic acid (DNA) affect how the disease responds to therapy in patients with ovarian, fallopian tube, or primary peritoneal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Studying samples of tissue in the laboratory from patients receiving talazoparib may help doctors learn more about the effects of talazoparib on cells and may help doctors understand how well patients respond to treatment.
详细描述
PRIMARY OBJECTIVES:
I. To explore basal levels and effects of talazoparib (BMN 673) on DNA copy number, loss of heterozygosity and mutation, and level of ribonucleic acid (RNA) and protein expression (together described as "molecular results") in homologous recombination-related pathways before and after treatment in women with primary advanced high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
SECONDARY OBJECTIVES:
I. To correlate molecular results to clinical endpoints including response and survival.
II. To correlate molecular results to pathologic endpoints including tumor volume and apoptosis.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with presumed advanced-stage high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma, based on the presence of carcinomatosis, and/or elevated cancer antigen 125 (CA125), and/or ovarian mass(es), or at the discretion of the treating physician
- •Medically able to undergo primary cytoreductive surgery, at least 7 days and up to 28 days after starting study drug, as determined by treating physician
- •No prior therapy for high-grade serous ovarian, fallopian tube, or primary peritoneal carcinoma
- •Patients must be able to swallow and tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of BMN 673 (e.g. uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome; ulcerative disease)
- •Absolute neutrophil count >= 1,500/mcL (measured within 28 days prior to entry/ randomization)
- •Hemoglobin >= 9 gm/dL (measured within 28 days prior to entry/ randomization)
- •Platelets >= 100,000/mcL (measured within 28 days prior to entry/ randomization)
- •Total bilirubin =< 1.5 X upper limit of normal (ULN) (measured within 28 days prior to entry/ randomization)
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal unless the liver is involved with tumor, in that case, ALT/AST must be =< 5 x upper limit of normal (measured within 28 days prior to entry/ randomization)
- •Creatinine clearance >= 50 mL/min (assessed by Cockcroft Gault estimation) (measured within 28 days prior to entry/ randomization)
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Women of child-bearing potential and their partners must agree to use contraception (hormonal or barrier method of birth control; abstinence) from the time of study entry until 30 days after the last dose of study medication; women of child-bearing potential (intact uterus) should have a negative serum pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; female patients must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
- •Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 consecutive months following cessation of all exogenous hormonal treatments
- •Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation; male partners should be instructed to use contraception during the study period
- •Women must not breast-feed while taking the study medications
- •Patients must be able to understand and willing to sign an informed consent
排除标准
- •Prior treatment for ovarian, fallopian tube, or primary peritoneal cancer
- •Receipt of any other investigational agents or any additional anti-cancer agents
- •Significant symptom burden from presumed diagnosis including large volume ascites, pain requiring narcotic medication, or shortness of breath on exertion
- •Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
- •As judged by the investigator, any evidence of severe or uncontrolled systemic diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease], uncontrolled chronic renal diseases [glomerulonephritis, nephritic syndrome, Fanconi syndrome or renal tubular acidosis]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension (blood pressure >= 140/90), active bleeding diatheses or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus; screening for chronic conditions is not required
- •As judged by the investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
研究组 & 干预措施
BMN 673
干预措施: Laboratory Biomarker Analysis (Other)
BMN 673
干预措施: BMN 673 (Drug)
结局指标
主要结局
Change in deoxyribonucleic acid (DNA) copy number
时间窗: Baseline to the day of tumor reductive surgery
Will use descriptive statistics and graphical methods to summarize the change in DNA copy number. Will summarize these changes for untreated patients. Will use a paired t-test to test that mean changes are different from 0. Will test median changes with a Wilcoxon signed-rank test. Will use a 2-sample t-test to compare mean changes between treated and untreated patients. Will compare median changes between treated and untreated patients with a Wilcoxon rank sum test.
Change in ribonucleic acid (RNA) protein expression
时间窗: Baseline to the day of tumor reductive surgery
Will use descriptive statistics and graphical methods to summarize the change in RNA protein expression. Will summarize these changes for untreated patients. Will use a paired t-test to test that mean changes are different from 0. Will test median changes with a Wilcoxon signed-rank test. Will use a 2-sample t-test to compare mean changes between treated and untreated patients. Will compare median changes between treated and untreated patients with a Wilcoxon rank sum test. Will use McNemar's test to compare the changes based on homologous recombination deficiency (HRD) assay results.
次要结局
- Overall survival(Up to 3 years)
- Tumor response(Up to 30 days)
- Tumor volume(Up to 30 days)
- Apoptosis(Up to 30 days)
- Completion Rate of BMN 673 to determine feasibility(Up to 30 days)
- Incidence of adverse events(Up to 30 days)
- Proportion of patients that exhibit an increase (or decrease) in RNA protein expression greater than 50%(Baseline to the day of tumor reductive surgery)
- Change in DNA copy number(Baseline to the day of tumor reductive surgery)
- Change in RNA protein expression(Baseline to the day of tumor reductive surgery)