Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 5
- 主要终点
- Determine MTD and RP2D of the Combination of BKM120 and Olaparib, and the Combination of BYL719 and Olaparib
研究概览
简要总结
This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational combination of drugs. Phase I studies also try to define the appropriate dose of the investigational combination to use for further studies. "Investigational" means that the combination of these drugs is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved either of these drugs nor the combination of being tested for use in patients, including people with your type of cancer.
BKM120, BYL719 and olaparib are drugs that may stop cancer cells from growing abnormally. These drugs when combined in laboratory experiments with animals, have demonstrated anti-cancer activity. Information from these other research studies suggests that the following agents BKM120, BYL719 and olaparib, may help to shrink tumor cells in the types of cancers being studied in this research study.
In this research study, the investigators are looking for the highest dose that can be given safely and also to see if the combination of BKM120 or BYL719 and olaparib is effective in treating your type of cancer.
详细描述
During this study, additional tests will be performed on a sample of your original tumor that has been stored in your institutions tissue banks. These tests will be performed on tumor tissue samples from previous biopsies or surgeries for your cancer. The research done on these samples will involve looking at DNA and proteins in your cancer to see if researchers can learn more about your type of cancer and understand how this combination of drugs might work on your tumor. Testing of this sample will not require you to undergo any additional research procedures.
Approximately 2 tablespoons of blood will be collected for research testing. This testing will involve looking at DNA and proteins in your blood to compare them with those seen in your cancer. This will be drawn before you begin taking the study drug.
You may also participate in an optional blood test for the BRCA gene. The BRCA gene test is a blood test that uses DNA analysis to see changes in either one of two breast cancer genes, known as BRCA1 or BRCA2. After having a BRCA gene test performed, you learn whether you carry an inherited BRCA gene mutation. If your blood is tested for the BRCA gene, the results will be reported to your study doctor who will share the results with you and provide information related to your personal risk of breast cancer. Having a BRCA gene mutation is rare, occurring in only about 1 in 1000 people. Inherited BRCA gene mutations are responsible for less than 5 to 10 percent of breast cancers and about 10 to 15 percent of ovarian cancers.
Participants in the dose expansion portion of the study may be asked to have a tumor biopsy done. The dose expansion phase for the combination of BKM120 and Olaparib has been determined. The combination of BYL719 and Olaparib is currently in the dose escalation phase and the dose expansion phase has not been determined. Before and after you begin taking BKM120 (or BYL719) and olaparib, your doctor may also ask you to participate in an optional study where you would have tumor biopsies done.
Participation in the tumor biopsy and blood test for the BRCA gene are optional, and whether you consent or refuse to undergo these additional tests will not affect your participation in the main research study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically or cytologically confirmed recurrent high grade serous ovarian cancer or triple negative breast cancer
- •Subjects with recurrent, metastatic triple negative breast cancer must have had at least 1 chemotherapy regimen for metastatic breast cancer or have developed metastatic breast cancer within 1 year of completion of adjuvant chemotherapy
- •Prior therapy for high grade serous ovarian cancer subjects must have included a first-line platinum-based regimen
- •At least 4 weeks since prior radiation therapy, 3 weeks since prior chemotherapy and 6 weeks if the last regimen included BCNU or mitomycin C
- •At least 4 weeks since any small-molecular kinase inhibitors or any other type of investigational agent
- •Life expectancy of at least 4 months
- •Able to swallow and tolerate oral medications
排除标准
- •Evidence of bowel obstruction, abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of study entry
- •Current dependency on IV hydration or total parental nutrition
- •Diabetes mellitus unless well controlled
- •Pregnant or breast feeding
- •History of grade 3 or 4 toxicities with previous PI3kinase inhibitor or PARP inhibitor
- •Current or active dermatologic diagnoses that would preclude interpretation of skin toxicities of BKM120
- •Receiving any medications or substances that are strong inhibitors or inducers of CYP3A4
- •History of cardiac dysfunction or disease
- •Persistent toxicities (greater than or equal to CTCAE grade 2) caused by previous cancer therapy
- •Major surgery within 14 days of starting study treatment
- •Evidence of coagulopathy or bleeding diathesis
- •History of major depressive episode, bipolar disorder, obsessive/compulsive disorder, schizophrenia, history of suicide attempt or ideation or homicide/homicidal ideation
- •CTCAE grade 3 or greater anxiety
- •Uncontrolled, intercurrent illness
- •Known HIV positive and on combination antiretroviral therapy
- •Receiving chronic treatment with steroids or another immunosuppressive agent
研究组 & 干预措施
Arm BKM
BKM120 and Olaparib
干预措施: BKM120 and Olaparib (Drug)
Arm BYL
BYL719 and Olaparib
干预措施: BYL719 and Olaparib (Drug)
结局指标
主要结局
Determine MTD and RP2D of the Combination of BKM120 and Olaparib, and the Combination of BYL719 and Olaparib
时间窗: 2 years
To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of BKM120 and olaparib, and the combination of BYL719 and olaparib in patients with recurrent TNBC and HGSC.
次要结局
- Determine preliminary activities of these combinations at the MTD and RP2 dose(2 years)
- Determine the overall Safety and Observed Toxicities of combining BKM120 and Olaparib, and combining BYL719 and Olaparib(2 years)
- Exploratory Translational Endpoints(2 years)
- Determine Pharmacokinetics of BKM120 and Olaparib, and BYL719 and Olaparib(2 years)
研究者
Ursula A. Matulonis, MD
Principal Investigator
Dana-Farber Cancer Institute