A Phase I Study of Veliparib (ABT-888) in Combination With Low-Dose Fractionated Whole Abdominal Radiation Therapy (LDFWAR) in Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis With Two Additional Dose Levels in Patients With Epithelial Ovarian, Fallopian or Primary Peritoneal Cancers and Intra-Abdominal Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 3
- 主要终点
- Maximum tolerable dose defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
研究概览
简要总结
This phase I trial studies the side effects and best dose of veliparib when given together with radiation therapy in treating patients with advanced solid malignancies (abnormal cells divide without control and can invade nearby tissues) with peritoneal carcinomatosis, epithelial ovarian, fallopian, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. Giving veliparib with radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerable dose of veliparib in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with peritoneal carcinomatosis from advanced solid malignancies. At dose levels 5 and 6: to determine the maximum tolerable dose of veliparib in combination with LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancers with intraabdominal disease.
II. Determine the safety and toxicity of the combination of veliparib in conjunction with LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies; at dose levels 5 and 6: to determine the safety and toxicity of veliparib in combination with LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancers with intraabdominal disease.
SECONDARY OBJECTIVES:
I. Assess clinical activity of veliparib plus LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies as assessed by response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. At dose levels 5 and 6: to assess the clinical activity of veliparib plus LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancer and intraabdominal disease as assessed by response rate by RECIST 1.1 criteria.
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
- •Dose levels 1-4 must have histologically proven solid malignancy that is metastatic or unresectable with metastatic peritoneal carcinomatosis; as this entity may be difficult to image, peritoneal disease can be documented through other modalities such as operative notes, clinical notes/symptoms, etc as well as imaging
- •Dose levels 5 and 6 will be open only to patients with recurrent or persistent primary epithelial ovarian, fallopian or peritoneal cancers; at these dose levels, measurable disease in the abdominal cavity must be present but peritoneal carcinomatosis is not required for eligibility
- •Patients must have failed first line standard therapy or have no acceptable standard treatment options; for patients on dose levels 5 and 6, patients may be platinum sensitive, platinum resistant or platinum refractory
- •Ability to understand and the willingness to sign a written informed consent document
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Life expectancy of greater than 3 months
- •Absolute neutrophil count (ANC) >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
- •Creatinine =< 1.5 x ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Calcium within normal limit (WNL)
- •No surgery, hormonal therapy or chemotherapy within four weeks; for dose levels 5 and 6, patients receiving mitomycin C or nitrosoureas must discontinue treatment 6 weeks prior to registration and any hormonal treatment directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
- •No previous abdominal radiation; if the patient has received previous pelvic radiation there should not be any overlap between the current and previous radiation fields
- •Toxicities of prior chemotherapy recovered to grade 1 or less except for stable grade 2 peripheral neuropathy
- •Negative pregnancy test if premenopausal; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Archival tumor sample collection with a tumor block is required for all enrolled patients when available; this will not be required for patients on dose levels 5 and 6; if no block can be released per institutional policy, 10 to 20 unstained slides may be substituted; slides should have a positive charge and a thickness of 3 to 5 microns; if the only tissue sample available is a fine needle aspirate (FNA), the patient will still be considered eligible
- •Patients with central nervous system (CNS) metastases to be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
- •For patients in dose levels 5 and 6, BRCA testing results, if previously performed, should be attained; if no BRCA testing has been performed, patients may be referred to a genetic counselor and will have detailed family history performed as part of the screening process
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients who are currently receiving any other investigational agents
- •Brain metastases: patients with treated and stable brain metastasis for 3 months, off steroids will be eligible
- •Patients who demonstrate any clinical evidence of bleeding
- •Patients who have demonstrated an inability to swallow oral medications
- •Patients who currently have an active gastrointestinal obstruction, have had a gastrointestinal obstruction within the last 30 days prior to enrollment and/or are actively requiring parenteral nutrition are excluded; patients who have had a history of any prior gastrointestinal obstruction requiring surgical intervention are also excluded
- •Patients who have a known hypersensitivity to the components of the study drug, its analogs or drugs of a similar chemical or biologic composition
- •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
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
- •Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- •Patients who have uncontrolled ascites
- •Patients with active seizures or a history of seizure are not eligible
- •Patients previously treated with poly (ADP-ribose) polymerase 1 (PARP) inhibitors
研究组 & 干预措施
Treatment (veliparib, LDRWAR)
Patients receive veliparib PO BID on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (veliparib, LDRWAR)
Patients receive veliparib PO BID on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Treatment (veliparib, LDRWAR)
Patients receive veliparib PO BID on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
Treatment (veliparib, LDRWAR)
Patients receive veliparib PO BID on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Veliparib (Drug)
结局指标
主要结局
Maximum tolerable dose defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
时间窗: 28 days
Reported with exact binomial proportions and 95% confidence intervals.
次要结局
- Clinical activity assessed by response (complete, partial, and overall), measured by RECIST 1.1 criteria(Up to 4 years)
- Changes in quality of life, assessed using the QLQC-30 standardized questionnaire(From baseline to 4 years)
- Microsatellite instability (MSI)(Baseline)
- Presence of DNA repair proteins(Baseline)
- Proportion of toxicities of the combination of veliparib and LDRWAR as graded by the NCI CTCAE version 4.0(Up to 4 weeks after completion of study treatment)