IMP321 Phase I Study in Metastatic Breast Carcinoma Patients Receiving First-line Paclitaxel
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 5
- 主要终点
- Evaluate clinical and laboratory safety and tolerability profiles
研究概览
简要总结
Open label, non-randomized, fixed dose-escalation phase I study, performed in ambulatory setting in patients receiving as a first line chemotherapy for metastatic breast carcinoma the standard 6 cycles of weekly paclitaxel (80 mg/m² at D1, D8 and D15 of a 4-week cycle). Three IMP321 doses (0.25, 1.25 and 6.25 mg) will be tested and given at D2 and D16 of this 4-week cycle, for 6 courses.
详细描述
This study is an open label, non-randomized, fixed dose-escalation phase I study, performed in ambulatory setting with patients receiving as a first line chemotherapy for metastatic breast carcinoma the standard 6 cycles of paclitaxel (80 mg/m² at D1, D8 and D15 of every 4-week cycle). Twenty mg i.v. dexamethasone will be given in the first cycle before each paclitaxel infusion. Corticosteroids will not be administered after the first chemotherapy cycle if the first 3 i.v. infusions of paclitaxel have been well tolerated.
Three IMP321 dose levels (0.25, 1.25 and 6.25 mg) will be evaluated in three cohorts of at lesat 8 patients. At any given dose level the patients will be administered one dose every two weeks for a total of 24 weeks (12 injections in total), separated by 13-day intervals free of IMP321 administration.
The study drug will be given by subcutaneous injection:
- Cohort A: 0.25 mg s.c.
- Cohort B: 1.25 mg s.c.
- Cohort C: 6.25 mg s.c.
The repeated single doses will be administered on D2 and D16 of the 4-week cycles, on the day which follows chemotherapy.
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
- •Patients with stage IV breast adenocarcinoma, histologically proven by biopsy of the primary tumor and/or a metastasis.
- •Female not pregnant (or with negative pregnancy test) or male.
- •Fertile patients must use effective contraception during and for 3 months after drug administration.
- •18 years or above.
- •ECOG performance status 0-
- •Expected survival longer than three months.
- •Resolution of toxicity of prior therapy to grade < 2 (except alopecia).
- •With or without prior adjuvant or neoadjuvant chemotherapy (authorized).
- •With or without hormone therapy in adjuvant and/or the advanced setting (authorized).
- •Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
- •Biphosphonate therapy must have started at least 4 weeks prior to first dosing of the study drug.
- •Asthma or chronic obstructive pulmonary disease allowed provided daily systemic corticosteroid therapy is not required.
- •Total white cell count ≥ 3.109/L.
- •Platelet count ≥ 100.109/L.
- •Hemoglobin > 9 g/dL or > 5.58 mmol/L.
- •Serum creatinine < 160 µmol/L.
- •Total bilirubin < 20 mmol/L, except for familial cholemia (Gilbert's disease).
- •Serum ASAT and ALAT < 3 times the upper limit of normal or < 5 times upper limit of normal if liver metastases are present.
- •Able to give written informed consent and to comply with the protocol.
排除标准
- •Prior chemotherapy for metastatic breast adenocarcinoma.
- •Disease-free interval < 12 months from last dose of adjuvant chemotherapy.
- •Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
- •Inflammatory carcinoma.
- •Systemic chemotherapy, hormone or endocrine therapy given as breast cancer therapy within 30 days prior to first dosing of the study drug.
- •Any investigational drug within 30 days prior to first dosing of the study drug.
- •Candidate for treatment with trastuzumab or administration of trastuzumab within 30 days prior to first dosing of the study drug.
- •Known cerebral or leptomeningeal metastases.
- •Pregnancy or breast feeding.
- •Serious intercurrent infection within the 30 days prior to first dosing of the study drug.
- •Motor or sensory peripheral neuropathy ≥ 2 according to the National Cancer Institute criteria.
- •Congestive heart failure.
- •Active acute or chronic infection.
- •Active autoimmune disease requiring immunosuppressive therapy.
- •Known HIV positivity.
- •Life threatening illness unrelated to cancer.
- •Previous malignancies within the last two years other than breast carcinoma, successfully treated squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated with cone biopsy.
- •Previous history of major psychiatric disorder requiring hospitalization or any current psychiatric disorder that would impede the patient's ability to provide informed consent or to comply with the protocol.
- •Corticosteroids unless used as substitutive therapy or before each injection of paclitaxel.
- •Past history of severe allergic episodes and/or Quincke edema.
- •Past or present history of any organic disorder likely to modify absorption, distribution or elimination of the study drug.
- •Alcohol or substance abuse disorder.
- •Radiotherapy within the 30 days prior to first dosing of the study drug.
结局指标
主要结局
Evaluate clinical and laboratory safety and tolerability profiles
时间窗: 6 months
Determine pharmacodynamic parameters
时间窗: 6 months
次要结局
- Objective response rate (OR) using RECIST criteria(6 months)