First-in-man Clinical Trial to Assess Safety and Tolerability of CEB-01 PLGA Membrane in Patients With Recurrent or Locally Advanced Retroperitoneal Soft Tissue Sarcoma After Surgery
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 5
- 主要终点
- Recommended Doses for Phase II (Maximum tolerated dose)
研究概览
简要总结
This is an open label, first-in-man clinical trial to assess safety and tolerability of CEB-01 PLGA membrane in patients with recurrent or locally advanced retroperitoneal soft tissue sarcoma after surgery.
The trial will be conducted in 3 dose-escalation cohorts (3 patients each, enrolling patients one by one, after 4 weeks of observation and agreement of Scientific Committee and DMC) and in an expansion cohort, using the highest safe and tolerable dose. The study will follow a 3+3 modified design; dose escalation will follow a modified Fibonacci method. CEB-01 carrying a SN-38 dose between 9 and 36 mg will be placed in the surgical bed at the time of tumor resection.
详细描述
CEB-01 is a poly(lactic-co-glycolic acid) (PLGA) polymeric drug with a delivery system loaded with SN-38, and will be placed in the surgical bed at the time of tumor resection.
CEB-01 carrying a SN-38 dose between 9 and 36 mg will be administered. CEB-01 will be placed on all surfaces that were in contact with and/or were infiltrated by the tumor.
Confirmatory central reviewing of diagnosis will be performed for all patients, using tumor samples obtained during surgery; additionally, patients will also be included according to local Pathological Anatomy (PA) diagnosis.
Patients will be followed-up once every week during the first 8 weeks of the study, and then every 2 weeks up to 12 weeks after implantation of CEB-01. Thereafter, follow-up schedule will be as per normal practice until study completion.
Efficacy assessment will be performed by Magnetic Resonance Imaging (MRI) [Computed tomography (CT) scan and Positron Emission Tomography (PET-CT) are also allowed] according to RECIST 1.1 criteria. Baseline image determination will be performed at week 12 (±3 days) after surgery; if the image analysis is not conclusive due to wound healing in the tumor bed, it will be repeated on week 16 (±3 days) post-surgery, and every 12 weeks thereafter.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Age >18 years.
- •Histologically confirmed diagnosis of locally advanced (T3 -T4, American Joint Committee on Cancer (AJCC)/primary tumor, regional lymph nodes, and distant metastases staging system (TMN) 8th Edition) and/or relapsed (any) retroperitoneal soft tissue sarcoma (liposarcoma, leiomyosarcoma, a solitary fibrous tumor (SFT), pleomorphic sarcoma, or a malignant nerve sheath tumor). Patients with local advanced (T3 -T4,AJCC/TMN 8th Edition) and/or relapse and metastatic disease who are candidates for local surgery without option of systemic treatment, are also eligible for the trial.
- •Pathology specimens available for centralized review. Submission of formalin-fixed paraffin-embedded (FFPE) tumor tissue for central reviewing is required; if a FFPE block cannot be provided, then 10 unstained, positively-charged slides of 4-5 um thickness must be submitted.
- •Size of tumor (visible or previously inadequately resected) >5 cm at instrumental staging (CT, MRI).
- •Normal liver, renal, hematological, and cardiac function as defined by biochemical and hematological parameters as follows: Hb >11 g/dL, platelets >100.000/mm3, White Blood Cells (WBC) >3000/mm3, neutrophil count >1500/mm3, albumin >3.0 g/dl, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) <2.5 times the upper limit of normality (ULN), bilirubin <2 times the ULN, creatinine <1.5 mg/dl or creatinine clearance > 60 ml/min.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status <
- •No concomitant radiotherapy or chemotherapy planned.
- •Life expectancy greater than 6 months.
- •Female subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at time of screening.
- •Men and women of childbearing potential must be willing to use adequate contraception throughout the study and for 3 months after surgery.
- •Ability to understand and the willingness to sign a written informed consent document; subject has signed an Informed Consent Form (ICF) prior to any screening procedures and is able to comply with protocol requirements.
排除标准
- •Pregnancy or lactation. Note: Pregnant women are excluded from this study; if the patient is a lactating mother, breastfeeding should be discontinued.
- •Other malignancies within past 5 years, with the exception of carcinoma in situ of cervix and basocellular skin cancers treated with eradicating intent.
- •Serious psychiatric disease that precludes informed consent or limits compliance
- •Medical condition limiting survival to less than 6 months.
- •Uncontrolled bacterial, viral or fungal infection.
- •Active viral hepatitis or chronic liver disease.
- •Impossibility of ensuring adequate follow-up.
- •Contraindication to magnetic resonance imaging (MRI), including presence of a pacemaker or an aneurysm clip, severe claustrophobia, a known reaction to the gadolinium contrast dye, or body weight that could interfere with the feasibility of a MRI.
- •Major surgery within 14 days prior to starting study drug or still in recovery after experiencing surgical complications; neither tumor biopsy nor central line insertion are considered a major surgery.
- •Unable or unwilling to stop the use of herbal supplements; the use of nutritional supplements may be allowed after review by a study pharmacist to confirm no significant risk of interaction with eribulin or radiation.
- •Other relevant concomitant illnesses.
- •Patients previously treated with Irinotecan.
研究组 & 干预措施
Cohort 1
CEB-01 with total SN-38 dose: 9 mg
干预措施: CEB-01 membrane loaded with SN-38 (Drug)
Cohort 2
CEB-01 with total SN-38 dose: 18 mg
干预措施: CEB-01 membrane loaded with SN-38 (Drug)
Cohort 3
CEB-01 with total SN-38 dose: 36 mg
干预措施: CEB-01 membrane loaded with SN-38 (Drug)
结局指标
主要结局
Recommended Doses for Phase II (Maximum tolerated dose)
时间窗: Through 2 weeks
The number of patients experiencing dose limiting toxicities during the Dose Limiting Toxicities (DLT) observation period of 2 weeks.
次要结局
- Progression Free Survival (PFS)(Through study completion, average 2 years)
- Frequency of Adverse Events (AEs) (Safety)(Through study completion, average 2 years)
- Time to local relapse (TTLR)(Through study completion, average 2 years)
- Quality of life: EORTC QLQ 30(Prior to surgery, at month 1 and month 3 after surgery)
- Frequency of Treatment Related Adverse Events (TRAEs) (Toxicity)(Through study completion, average 2 years)
- Overall Survival (OS)(until 24 months of Follow Up (FU))(Through study completion, average 2 years)