Phase I/II Study of BYL719 and Nab-Paclitaxel in Subjects With Locally Recurrent or Metastatic HER-2 Negative Breast Cancer

Priyanka Sharma4 个研究点分布在 1 个国家目标入组 43 人开始时间: 2015年2月最近更新: 2022年6月7日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Priyanka Sharma
入组人数: 43
试验地点: 4
主要终点: Phase I: Recommended Phase II Dose (RP2D) of BYL-719 (Alpelisib) + Nab-paclitaxel to be Used in Combination to Treat Advanced HER2-negative Breast Cancer

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Investigate the use of BYL719 (alpelisib) as combination therapy with Nab-Paclitaxel in locally recurrent or metastatic HER-2 negative breast cancer.

详细描述

Breast cancer is the most common cancer and the second leading cause of cancer related death in American women. Despite recent improvement in the treatment of breast cancer, 40,000 women still die each year in the US as a result of breast cancer. Chemotherapy (usually consisting of sequential single agent) remains the backbone of treatment for patients with HER-2 negative metastatic breast cancer. A majority of patients show an initial response to treatment, but all eventually show disease progression.

The purpose of this study is to determine the highest dose of BYL719 (alpelisib) combined with Nab-Paclitaxel that results in no serious side effects. The safety and effectiveness of BYL719 combined with Nab-Paclitaxel to treat patients with HER-2 negative metastatic breast cancer will be assessed, along with the determination of how long this drug combination will keep the disease from getting worse.

The study will be done in two parts:

Part 1 will determine the highest dose of BYL719 that is safe and tolerable to take in combination with Nab-Paclitaxel. Part 1 will be completed before Part 2 begins.

Part 2 will investigate whether taking BYL719 (at the dose determined in Part 1) + Nab-Paclitaxel is safe and effective for patients with HER-2 negative metastatic breast cancer.

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

•Ability to understand and the willingness to sign a written Informed Consent Form.
•Age ≥ 18 years
•Histologically proven HER-2 negative breast cancer (HER-2 negative defined as HER IHC 0 or 1+ and/or HER-2 FISH negative); HER-2 negative breast cancer includes hormone positive (ER and/or PR positive) breast cancer and TNBC
•HER-2 negative breast cancer that at the time of study entry is either stage III (locally advanced) disease not amenable to curative therapy or stage IV disease. Histological confirmation of recurrent/metastatic disease is encouraged but not required if clinical evidence of stage IV disease is available
•Have measurable (defined as at least one lesion that can be accurately measured in at least one dimension [longest diameter to be recorded] with minimum lesion size of ≥ 2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
•No limitations to number of prior chemotherapies for metastatic disease. Treatment with prior taxanes (except Nab-Paclitaxel) is allowed as long as it has been 6 months or more since exposure to prior taxane.
•NOTE: For subjects who are, or who have previously received endocrine therapy for breast cancer, the treating investigator will decide how many days should pass between the last dose of endocrine therapy and the first dose of study treatment.
•All patients should have received at least one line of chemotherapy in either the advanced or adjuvant setting and hormonal therapy (where appropriate)
•Performance status of 2 or better as per ECOG criteria (See Appendix A for details)
•Subject is able to swallow and retain oral medicines
•Adequate marrow and organ function as defined below (labs must be performed within 14 days of subject registration)
•Absolute neutrophil count ≥ 1500/uL
•Platelets 100,000/uL (no transfusion allowed within 2 weeks)
•Hemoglobin > 9 g/dL (which may be reached by transfusion)
•Total bilirubin within normal range or ≤ 1.5X IULN if liver metastases are present or total bilirubin ≤ 3.0X IULN with direct bilirubin within normal range in subjects with well-documented Gilbert's Syndrome, which is defined as presence of unconjugated hyperbilirubinemia with normal results from CBC (including normal reticulocyte count and blood smear), normal liver function test results and absence of other contributing disease processes at the time of diagnosis
•AST(SGOT)/ALT(SPGT) ≤ 2.5X IULN or ≤ 5X IULN if liver metastases are present
•Serum creatinine ≤ 1.5X IULN
•INR ≤ 1.5
•Fasting plasma glucose ≤ 140 mg/dL or 7.8 mmol/L (NOTE: Fasting whole blood glucose testing is acceptable if fasting plasma glucose is not feasible.)
•HBA1c ≤ 8%
•Potassium, calcium (corrected for serum albumin) and magnesium within IULN
•Serum Amylase < 2 x ULN and serum lipase within normal limits
•IV bisphosphate and denosumab for bony metastatic disease will be allowed
•Prior palliative radiation therapy to bony metastases is allowed. There should be a minimum of 14 days between the end of radiation treatment and start of study treatment
•Subjects with previously treated brain metastases who are free of CNS symptoms and are > 3 months from treatment of brain metastases are eligible Subjects should be > 2 weeks from prior systemic chemotherapy for breast cancer AND should have recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy prior to study entry NOTE: For subjects who are, or who have previously received endocrine therapy for breast cancer, the treating investigator will decide how many days should pass between the last dose of endocrine therapy and the first dose of study treatment.
•Women of child bearing potential (WOCBP) and their partners must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. After confirmation of negative pregnancy test at screening, should a WOCBP become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician and the investigator immediately.
•WOCBP are defined as any females (regardless of sexual orientation, having undergone tubal ligation, or remaining celibate by choice) who meet the following criteria:
•Have not undergone a hysterectomy or bilateral oophorectomy OR
•Have not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)
•Exclusion criteria:
•Subject has any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications
•Subject is pregnant or lactating
•Subject has previously been treated with Nab-Paclitaxel NOTE: Subjects who have had previous treatment with Nab-Paclitaxel will NOT be excluded if given in the adjuvant or neoadjuvant setting Only in the metastatic setting, will subjects previously treated with Nab-Paclitaxel be excluded from this trial. Exceptions may be made for subjects who discontinued treatment with a previous Nab-Paclitaxel inhibitor for reasons other than progression and as long as it has been > 12 months since discontinuation of the previous Nab-Paclitaxel. This exception will require prior approval from the study PI at KUMC.
•Subject has inflammatory breast cancer
•Subject has a known hypersensitivity to any of the excipients of Nab-Paclitaxel or BYL719/alpelisib
•Subject has a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer)
•Subject has clinically manifest diabetes mellitus or documented steroid-induced diabetes mellitus
•Subject has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
•Subject is classified into Child-Pugh class C
•Subject has a known history of HIV infection (testing not mandatory)
•Subject has active, uncontrolled infection
•Subject has symptomatic/untreated CNS disease
•Subject has ≥ Grade 2 peripheral neuropathy
•Subject has active cardiac disease or a history of cardiac dysfunction including any of the following:
•Unstable angina pectoris within 6 months prior to study entry
•Symptomatic peritonitis
•Documented myocardial infarction within 6 months prior to study entry
•History of documented congestive heart failure (New York Heart Association functional classification III-IV)
•Documented cardiomyopathy
•Subject has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO)
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排除标准

未提供

研究组 & 干预措施

Dose level 1 BYL-719/alpelisib (250mg)+Nab-paclitaxel

Experimental

BYL-719 (alpelisib): 250mg daily on day 1-28

Nab-paclitaxel: 100mg/m2 IV days 1, 8, 15 of each 28 day cycle (Window for Nab-paclitaxel is +/- 1 day)

干预措施: BYL-719 (alpelisib) (Drug)

Dose level 1 BYL-719/alpelisib (250mg)+Nab-paclitaxel

Experimental

BYL-719 (alpelisib): 250mg daily on day 1-28

Nab-paclitaxel: 100mg/m2 IV days 1, 8, 15 of each 28 day cycle (Window for Nab-paclitaxel is +/- 1 day)

干预措施: Nab-paclitaxel (Drug)