NCT02398058已完成1 期
A Phase Ib Study on the Combination of Trabectedin and Olaparib in Unresectable Advanced/Metastatic Sarcomas After Failure of Standard Therapies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- maximum tolerated dose
研究概览
简要总结
This is a Phase 1b, multi-site, open-label, non-randomized clinical trial evaluating the safety, tolerability, and pharmacokinetics of escalating doses of olaparib and trabectedin in patients with unresectable advanced/metastatic sarcomas. Patients will continue to be treated on this combination regimen in the absence of disease progression, intolerable toxicity or patient's decision.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •written informed consent
- •histologically documented and not surgically resectable or metastatic sarcomas which progressed after first or further line treatments for relapsing disease
- •Measurable disease as defined by RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0/
- •ECOG PS 2 are eligible if depends solely on orthopedic problems
- •Estimated life expectancy of ≥ 4 months
- •Age ≥18 years
- •Adequate organ function: Hemoglobin > 10.0 g/dl; Absolute neutrophil count (ANC) >1,500/mm3; Platelet count >= 100,000/μl; Total bilirubin < 1.5 times the upper limit of normal (ULN); ALT and AST < 2.5 x ULN (< 5 x ULN for patients with liver involvement of their cancer); Alkaline phosphatase < 2.5 x ULN; PT-INR/PTT < 1.5 x ULN; Serum creatinine < 1.5 x ULN or creatinine clearance ≥ 50 ml/min; Albumin > 25 g/l; Creatine phosphokinase (CPK) < 2.5 x ULN
排除标准
- •Involvement in the planning and/or conduct of the study
- •Previous enrolment in the present study
- •Participation in another clinical study with an investigational product during the last month
- •Persistent toxicities (≥CTCAE grade 2) with the exception of alopecia, caused by previous anticancer therapies
- •Dementia or significantly altered mental status
- •Patients with any severe and/or uncontrolled medical conditions
- •HIV infection
- •Active clinically serious infections (> grade 2 NCI-CTCAE version 4.03).
- •Active viral hepatitis (HBV or HCV infection)
- •Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, does not require corticosteroid treatment, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry).
- •Patients with seizure disorders requiring medication (such as steroids or anti-epileptics)
- •Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days before the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 5 months after last dose of study drug
- •Patients with evidence or history of bleeding diathesis
- •Patients undergoing renal dialysis
- •Patients unable to swallow oral medications
- •Uncontrolled diabetes (fasting glucose > 2 x ULN)
- •Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). Topical or inhaled corticosteroids are permitted
- •Patients with a history of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer or other solid tumors curatively treated with no evidence of disease for ≥5 years.
- •Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of treatment start
- •Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy allowed)
- •Major surgery within 4 weeks of start of study
- •Prior exposure to the study drugs or their analogues
- •Patients with known hypersensitivity to trabectedin, olaparib or to their excipients
- •Patients can receive a stable dose of bisphosphonates for bone metastases before and during the study as long as these were started at least 4 weeks prior to treatment with the study drugs
- •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- •A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits
- •Corrected QT interval on the 12-lead ECG (QTc) >470 msec (Bazett Formula)
- •use of strong CYP3A4 inhibitors/inducers
- •Patients with myelodysplastic syndrome/acute myeloid leukemia
研究组 & 干预措施
Trabectedin plus olaparib
Experimental
All patients will be treated with trabectedin and olaparib in an open-label fashion.
The dosage of the drugs at which each patient is treated depends on the dose level reached at the time of enrollment.
干预措施: trabectedin (Drug)
Trabectedin plus olaparib
Experimental
All patients will be treated with trabectedin and olaparib in an open-label fashion.
The dosage of the drugs at which each patient is treated depends on the dose level reached at the time of enrollment.
干预措施: olaparib (Drug)
结局指标
主要结局
maximum tolerated dose
时间窗: from start up to 6 weeks
safety will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03
次要结局
- Best Overall Response(baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years)
- Clinical Benefit Rate(baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years)
- Overall Survival(baseline and up to 2 years)
- Biomarkers (composite outcome)(baseline, day 1-2-8-15 of each cycle up to 2 years)
- Duration of Tumor Response(baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years)
- Progression-Free Survival (PFS)(baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years)
- Pharmacokinetic of trabectedin (AUC)(baseline, days 1-2-3-4-5-8-15 of the first two cycles)
- Pharmacokinetic of olaparib (steady state profile and so maximum concentration, minimal concentration, and AUC will be calculated)(baseline, day -5 cycle 1, day 1 cycle 2, of the first two cycles)
- Growth Modulation Index(baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years)
- safety evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03(baseline up to 28 days after last dose of study treatment up to 2 years)
研究者
研究点 (3)
Loading locations...
相似试验
已完成
3 期
An Efficacy and Safety Study of Trabectedin Versus Doxorubicin-Based Chemotherapy in Participants With Translocation-Related Sarcomas (TRS)SarcomaNCT00796120Johnson & Johnson Pharmaceutical Research & Development, L.L.C.121
撤回
1 期
Trabectedin and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Resistant or Intolerant to a BTK InhibitorRefractory Chronic Lymphocytic LeukemiaRefractory Small Lymphocytic LymphomaNCT03884972M.D. Anderson Cancer Center
已完成
2 期
Safety and Efficacy Study of Trabectedin for the Treatment of Localized Myxoid / Round Cell LiposarcomaLiposarcoma,MyxoidNCT00579501Johnson & Johnson Pharmaceutical Research & Development, L.L.C.29
进行中（未招募）
1 期
combination of trabectedin and olaparib in ovarian cancer, fallopian tubes and primary of peritoneum already resistant to standard platinum drugsplatinum-resistant ovarian carcinoma or Fallopian tubes or primary of peritoneumMedDRA version: 21.1Level: LLTClassification code 10033131Term: Ovarian carcinomaSystem Organ Class: 100000004864EUCTR2018-000230-35-ITFONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA IRCCS66
进行中（未招募）
1 期
Clinical trial of trabectedin and low-dose radiation therapy in advanced/metastatic sarcomasCTIS2023-509215-81-00Asoc Grupo Espanol De Investigacion En Sarcomas72