Phase I/II Trial of S 81694 Administered Intravenously in Combination With Paclitaxel to Evaluate the Safety, Pharmacokinetic and Efficacy in Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 6
- 主要终点
- Abnormalities in heart rate (BPM (beat per minute))
研究概览
简要总结
The purpose of this study is to determine the safety profile, the maximum tolerated dose (MTD) and the associated dose-limiting toxicities (DLTs) of S 81694 in combination with paclitaxel in metastatic breast cancer (mBC) patients, and to investigate the antitumour activity of the combination in metastatic triple negative breast cancer (mTNBC) patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •For Phase I :
- •Histologically or cytologically confirmed metastatic breast cancer, refractory to any standard therapy or for which the standard therapy is considered unsuitable;
- •Patient must have at least one evaluable or measurable metastatic lesion (lesions as defined by revised Response Evaluation Criteria in Solid Tumors).
- •For Phase II :
- •Histologically or cytologically confirmed advanced inoperable triple negative breast cancer with no prior anticancer therapy regimen in metastatic setting;
- •Patient with a minimum washout period of 12 months following previous taxane based adjuvant therapy;
- •Patient must have at least one measurable metastatic lesion. Ascites, pleural effusion, and bone metastases are not considered measurable;
- •Acceptance of pre-treatment metastatic biopsies for all patients and on-treatment metastatic biopsies in selected centres.
- •For the whole study:
- •Male or female subjects aged ≥ 18 years old, or legal age of the majority in the country;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Estimated life expectancy of at least 3 months;
- •Adequate haematological function based on the last assessment performed within 7 days prior to the first IMP (investigational medicinal product) administration;
- •Adequate renal function based on the last assessment performed within 7 days prior to the first IMP administration;
- •Adequate hepatic function based on the last assessment performed within 7 days prior to the first IMP administration;
- •Female participant of childbearing potential must have a negative pregnancy test (serum) within 7 days prior to the first day of test drug administration. Effective contraception both for female patients of childbearing potential and male patients with parteners of childbearing potential.
排除标准
- •Other active malignancy within the last 3 years (except for basal cell carcinoma or a non-invasive/in situ cervical cancer or intra-mucosal gastro-intestinal cancers that were treated curatively);
- •Presence of grade ≥ 2 toxic effects (excluding alopecia) due to prior cancer therapy;
- •Known hypersensitivity to the IMP (S 81694 and paclitaxel) or their excipients;
- •Evidence of peripheral neuropathy of grade 2 or higher;
- •Participant previously received paclitaxel and discontinued due to toxicity related to paclitaxel;
- •Participant known as refractory to taxanes;
- •Any prior cancer therapy within 4 weeks or 5 half-life (whichever is the shorter) before the first IMP administration;
- •Participant with current, serious, uncontrolled infections;
- •Participant with brain metastasis or leptomeningeal metastasis (except patients with brain metastasis that have been stable post-radiation therapy and who are off steroids for > 2 months);
- •History of cardiac disease;
- •Uncontrolled arterial hypertension;
- •Presence of risk factors for torsades de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome);
- •Any clinically significant medical condition (e.g. organ dysfunction) or laboratory abnormality likely to jeopardize the patient's safety or to interfere with the conduct of the study, in the investigator's opinion.
研究组 & 干预措施
Combination therapy (S81694 + paclitaxel) phase I
Phase I: Single arm, non-randomized study in metastatic breast cancer patients. S81694 given intravenously every two weeks at different doses on D1 and D15 last for 28 days. The participants will also receive paclitaxel intravenously on D1, D8 and D15 last for 28 days.
干预措施: Combination therapy (S81694 + paclitaxel) phase I (Drug)
paclitaxel phase II
Phase II: Randomised phase II part , two-arm, in untreated metastatic triple negative breast cancer patients.
Paclitaxel given intravenously on D1, D8, and D15 at 80 mg/m² during a 28-day cycle.
干预措施: Paclitaxel (Drug)
Combination therapy (S81694 + paclitaxel) phase II
Phase II: Randomised phase II part , two-arm, in untreated metastatic triple negative breast cancer patients.
S 81694 given intravenously on D1 and D15 at recommended phase 2 dose (RP2D). Paclitaxel given intravenously on D1, D8, and D15 during a 28-day cycle.
干预措施: Combination therapy (S81694 + paclitaxel) phase II (Drug)
结局指标
主要结局
Abnormalities in heart rate (BPM (beat per minute))
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment
Abnormalities in body weight (Kg)
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment
Progression free survival (PFS) [based on Investigator review of the images according to RECIST 1.1]
时间窗: Through study completion, an average of 4 years
Efficacy criterion - time from the date of first study drug intake until the date of the investigator-assessed disease progression or death due to any cause whichever occurs first.
Abnormalities in body temperature (C°degree celsius)
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment
Abnormalities in respiration rate (cycles per minute)
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment
Safety and tolerability assessed by incidence of Adverse Events
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria - Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03
Abnormalities in blood pressure (mmHg)
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria - Treatment-emergent changes in physical examinations, ECOG performance status, at periodic intervals during the study and at End of Treatment
Abnormalities in physical examination and performance status (ECG) (mm/s)
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria
Incidence of DLTs (dose-limiting toxicities)
时间窗: Through study completion, an average of 4 years
Safety criterion - A DLT is defined as any toxicity attributable to S81694 or the combination that occurs before the end of Cycle 1
Abnormalities in laboratory tests (haematology, blood biochemistry and urinalysis)
时间窗: Through study completion, an average of 4 years
Safety and tolerability criteria disease progression according to RECIST v1.1 or death due to any cause
次要结局
- The PK (pharmacokinetic) profile of S 81694 and paclitaxel plasma concentration : Area under the plasma concentration-time curve (AUC)(Through study completion, an average of 3 years)
- Overall Response Rate (ORR) [ based on Investigator review of the images according to RECIST 1.1](Through study completion, an average of 4 years)
- Incidence of treatment-emergent adverse events (AEs) graded according to NCI CTCAE v4.03(Through study completion, an average of 4 years)
- The PK profile of S 81694 and paclitaxel plasma concentration : Maximum plasma concentration (Cmax)(Through study completion, an average of 3 years)
- The PK profile of S 81694 and paclitaxel plasma concentration : Minimum plasma concentration (Cmin)(Through study completion, an average of 3 years)
- The PK profile of S 81694 and paclitaxel plasma concentration : Elimination half-life (T½)(Through study completion, an average of 3 years)