Phase Ib of CC-5013 and Paclitaxel in Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 发起方
- Southern Europe New Drug Organization
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Define the MTD of the combination of CC-5013 and paclitaxel in patients with advanced solid tumors
概览
简要总结
This is a dose finding, open-label, uncontrolled, dose-escalation trial to determine the maximum Tolerated Dose (MTD) of the combination of CC-5013 (Lenalidomide)and paclitaxel in patients with advanced solid tumors.
Other purposes of the study are:
- Define the safety profile of the CC-5013 and paclitaxel given in combination
- Define the pharmacokinetics of CC-5013 and paclitaxel given in combination
- Define the pharmacodynamic effects of the combination by monitoring potential biomarkers of the different biological activities of each component of the regimen
- Define the optimal biological dose (OBD) and the dose recommended (RD) for phase II studies in selected tumor types (breast, ovary, prostate, NSCLC)
- Collect evidence of antitumor activity in selected tumor types
详细描述
The new immunomodulatory drugs (IMiD) derivatives of thalidomide (CC-5013 lenalidomide and CC4047 pomalidomide) are endowed of direct antitumor activity besides the indirect effects attributed to antiangiogenic, antiinflammatory and T-cell co-stimulatory properties.
Combination therapy with cytotoxic agents or other anticancer drugs could lead to additive or synergistic interactions and support their clinical development in tumor types in which the specific activities of IMiDs could be of potential value.
Combinations with weekly paclitaxel could be of interest because of its antiangiogenic activity, antitumor activity in prostate, NSCLC, ovary, breast cancer, tumor types in which IMiD could be of clinical value because of either enhancement of tumor specific immunity (ovary, prostate) or inhibition of Treg function (breast, NSCLC, ovary).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological/cytological diagnosis of solid tumors for which a treatment with paclitaxel could be indicated (preferentially ovary, breast, prostate, NSCLC)
- •Documented progression of the tumor in the 3 months preceding the study
- •Expected survival ≥ 3 months
- •Age 18-75 years
- •ECOG PS 0-1
- •measurable/evaluable disease during escalation phase, according to modified RECIST criteria. For patients with ovarian and prostatic cancer, tumor markers (CA125 for ovarian and PSA for prostatic) are accepted as only evidence. Measurable/evaluable disease is mandatory during the RD expansion phase
- •≤ 2 prior lines of chemotherapy for metastatic disease. For ovarian patients reintroduction of a platinum at relapse, after an initial response lasting \> 6 months is considered one chemotherapy regimen only
- •Adequate contraception for all fertile patients
- •Adequate hematological function as defined by: ANC ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin ≥ 10 g/dL.
- •Normal PTand INR; fibrinogen \> lower Normal Limit (LNL)
排除标准
- •History of DVT or coagulation disturbances
- •Need of treatment with oral anticoagulants or LMW heparin
- •Clinical resistance to taxanes defined as progression during therapy or within 6 months from the end of adjuvant treatment
- •Known or prior hypersensitivity to taxanes or drugs containing chemophor, or to thalidomide (or analogues)
- •Preexisting peripheral neuropathy \> grade 1
- •Concomitant treatment with non steroid anti-inflammatory agents (NSAIA), high dose steroids or immunosuppressants
- •Concomitant hormonal treatment (including those with antiandrogenic)
- •Radiotherapy involving \> 30% of the active bone marrow
- •Radiotherapy ≤ 4 weeks prior to enrolment
- •Other chemotherapy treatment ≤ 4 weeks prior to enrolment, at least 6 weeks for nitrosoureas or mitomycin C, or investigational drugs
研究组 & 干预措施
CC-5013 in combination with Paclitaxel
Cohorts of 3 evaluable patients will initially be entered within each dose level, sequentially. In each dose level the second and third patient will enter 2 weeks after the first one. The second and third patient may be treated simultaneously, except if a DLT is reported in the first patient, in which case the second and third patient should be treated sequentially, at least one week apart.
Dose escalation will be done when all the patients included in each DL will finish the first treatment cycle. Three additional patients will be sequentially entered (separated by one week each other) if one DLT is observed in cycle 1 among the first 3 patients entered within a dose level. If a DLT is observed in a second patient at this dose level, no further dose escalation will be allowed and the dose level will be considered the MTD.
Once the RD (one level below the MTD) has been defined, additional patients (up to 12) will be treated in order to confirm the safety profile of the combination.
干预措施: Lenalidomide (CC-5013) (Drug)
结局指标
主要结局
Define the MTD of the combination of CC-5013 and paclitaxel in patients with advanced solid tumors
时间窗: 4 weeks after the first drug administration
Number of Dose-Limiting Toxicities (DLTs)
次要结局
- Safety profile of the drug combination(from the first administration to 30 days after the trial end)
- Pharmacokinetics of CC-5013 and paclitaxel given in combination(untill 4 weeks after the first drug administration)
- the pharmacodynamic effects of CC-5013 and paclitaxel given in combination(from the first drug administration to 30 days after trial end)
- Evidence of antitumor activity in selected tumor types(From the first drug administration to 30 days after the trial end)