NL-OMON47387已完成不适用
A phase Ib dose-finding study of BYL719 plus everolimus and BYL719 plus everolimus plus exemestane in patients with advanced solid tumors, with dose-expansion cohorts in renal cell cancer (RCC), pancreatic neuroendocrine tumors (pNETs), and advanced breast cancer (BC) patients - BYL719+everolimus and BYL719 everolimus+exemestane in solid tumors
适应症
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- ovartis
- 入组人数
- 10
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 99（—）
入选标准
- •1. Tumor tissue available for the analysis of PI3K signaling.
- •2. ECOG PS * 2 at time of screening
- •3. Adequate bone marrow and organ function:
- •*Absolute Neutrophil Count (ANC) * 1.5 x 109/L
- •*Platelets * 100 x 109/L
- •* Hemoglobin * 90 g/L or * 5,85 mmol/L
- •* INR * 2
- •* Serum creatinine * 1.5 x ULN
- •* Total serum bilirubin * 2.0 mg/dL
- •* AST and ALT * 2.5 x ULN (or * 5 x ULN if liver metastases are present)
- •* Fasting plasma glucose (FPG) * 140mg/dL or * 7.8 mmol/L
- •* Cholesterol (fasting) *300 mg/dL OR *7.75 mmol/L AND fasting triglycerides *2.5x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
- •Escalation phase:
- •4. Histologically/cytologically confirmed metastatic and/or recurrent solid tumor for whom no standard therapy exists ;Specific additional Inclusion criteria for the doublet combination * expansion phase
- •RCC patients* cohort:
- •a. Histologically/cytologically confirmed RCC
- •b. Prior treatment with cytokines is allowed. A maximum of two prior therapies with VEGF-targeting agents for advanced recurrent/metastatic disease is allowed ;pNET patients* cohort:
- •a. Histologically/cytologically confirmed well or moderately differentiated pNET
- •b. Patient may have received prior and/or concurrent long-acting somatostatin analogue therapy: ;mTOR inhibitor-pretreated patients* cohort: :
- •a. Histologically and/or cytologically confirmed solid malignancy that is metastatic and/or recurrent. Patient has progressed to a prior mTOR inhibitor. Patient who had discontinued prior mTOR inhibitor treatment due to non-tolerable toxicities is not eligible.;Specific additional inclusion criteria for the triplet combination - escalation and expansion phases
- •a. Histologically and/or cytologically confirmed diagnosis of BC
- •b. Radiologic evidence of inoperable locally advanced, or metastatic BC
- •c. HER2-negative BC (based on most recently analyzed biopsy)
- •d. Known HR-positive status (either estrogen or progesterone)
- •e. Patient is a postmenopausal woman.
- •f. Patient whose disease is refractory to previous letrozole or anastrozole (recurrence during or within 12 months after the end of adjuvant treatment or progression during or within 1 month after the end of treatment for advanced disease).
- •g. Up to two prior chemotherapy regimens for locally advanced or metastatic disease. ;Specific additional inclusion criterion for the triplet combination:
- •a. Patient has identified PIK3CA mutational status as determined by ctDNA by a Novartis designated laboratory.
- •b. Patient may have received up to one prior chemotherapy regimen for locally advanced or metastatic disease.
- •NOTE: Prior targeted therapy including CDK4/6 inhibitor is allowed ;Specific inclusion criteria at the time of the cross-over
- •a. Patient randomized to the alpelisib and exemestane combination who has a radiologically documented progressive disease
- •b. (ECOG Performance Status * 2
- •c. Toxicities < grade 3 while receiving alpelisib and exemestane
- •d. No residual toxicity related to alpelisib or exemestane > Grade 1 prior to initiating the triplet combination.
排除标准
- •Dose-escalation and the dose-expansion phases
- •1. Patient has received previous treatment with a PI3K and/or AKT and/or mTOR inhibitor (e.g. sirolimus, temsirolimus, deforolimus). Note: Prior mTOR inhibitor treatment is allowed only in the expansion cohorts 3 and 5.
- •2. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
- •3. Patient with primary central nervous system (CNS) tumor or CNS tumor involvement.
- •However, CNS metastasis are allowed under the following conditions:
- •a. 4 weeks from prior therapy completion (including radiation and/or surgery for CNS tumor) to starting the study treatment, and
- •b. Clinically stable with respect to the CNS tumor at the time of screening, and
- •c. Not receiving steroid therapy
- •4. Patient with diabetes mellitus, or documented steroid-induced diabetes mellitus
- •5. Patient has a history of another malignancy within 2 years prior to starting study treatment, except for cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
- •6. Side effects (related to prior antineoplastic therapy) not recovered to grade 1 or better (except alopecia)
- •7. Several therapies including radiotherapy and surgery prior to start study treatment within specific timelines as described in the protocol section 5.3 (exclusion criteria 6 to 9)
- •8. Clinically significant cardiac disease or impaired cardiac function, such as:
- •a. Congestive heart failure New York Heart Association (NYHA) Grade * 2, left ventricular ejection fraction (LVEF) < 50%
- •b. History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, highgrade/ complete AV-blockage
- •c. Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), < 3 months prior to screening
- •d. QTcF > 480 msec on screening ECG
- •9. Any severe and/or uncontrolled medical condition (details specified in protocol section 5.3 exclusion criterion 11)
- •10. Use of medication with a known risk of prolonging the QT-interval or inducing Torsades de Pointes (TdP) Refer to protocol for details (Section 14.1, Table 14-3)
- •11. Use of medication known to be moderate or strong inhibitors or inducers of isoenzymes CYP34A or CYP2C8. Refer to protocol for details Refer to protocol (Section 14.1, Table 14-2);Specific inclusion criteria at the time of the cross-over
- •a. Patient randomized to the alpelisib and exemestane combination who has a radiologically documented progressive disease
- •b. Patient has ECOG PS * 2
- •c. Patient who experienced toxicities < grade 3 while receiving alpelisib and exemestane
- •d. Patient who has no residual toxicity related to alpelisib or exemestane > Grade 1 prior to initiating the triplet combination.
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