NCT03722342Unknown1 期
A Phase 1b, Open-Label, Safety and Tolerability Study of TTAC-0001 in Combination With Pembrolizumab in Patients With Recurrent Glioblastoma
PharmAbcine2 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2019年1月16日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Dose limiting toxicities
研究概览
简要总结
This is a phase 1b, open-Label clinical trial to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of TTAC-0001 administered in combination with pembrolizumab in patients with recurrent glioblastoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Diagnosed with primary glioblastoma by histopathological examination and confirmed recurrent glioblastoma by magnetic resonance imaging (MRI) scans after completing standard of care (Stupp protocol) concomitant temozolomide chemotherapy with radiotherapy (CCRT)
- •At least one confirmed measurable lesion by RANO criteria
- •Karnofsky Performance Status (KPS) ≥80
- •A person who satisfies the following criteria in haematologic, renal, and hepatic function tests performed within 7 days prior to screening:
- •Haematologic tests
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •Platelets ≥ 100 x 109/L
- •Haemoglobin ≥ 9.0 g/dL
- •Blood coagulation tests
- •Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (ULN)
- •Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
- •Hepatic function tests
- •Total bilirubin ≤ 1.5 x UNL
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis)
- •Renal function test
- •≤1.5 × ULN or creatinine clearance (CrCl) ≥30 mL/min for patient with creatinine levels >1.5 × institutional ULN
- •At least 12 weeks of expected survival time
- •The patient (or legally acceptable representative if applicable) is able and willing to provide written informed consent for the trial
排除标准
- •Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. (Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] controlled by curative therapy are not excluded)
- •Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
- •Has a history of (non-infectious) pneumonitis/interstitial lung diseases that required steroids or current pneumonitis/interstitial lung disease
- •Has an active infection requiring systemic therapy
- •Uncontrolled hypertension (systolic blood pressure [SBP]> 150 or diastolic blood pressure [DBP]> 90 mmHg)
- •Uncontrolled seizures
- •Class III or IV heart failure by New York Heart Association (NYHA) classification
- •Has oxygen-dependent chronic disease
- •Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.). Treated depression with ongoing antidepressant medication is not an exclusion
- •History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study drug
- •History of serious gastrointestinal haemorrhage within 6 months prior to start of study drug
- •History of severe arterial thromboembolic event within 12 months of start of study drug
- •Serious grade 4 venous thromboembolic event including pulmonary embolism
- •History of hypertensive crisis or hypertensive encephalopathy
- •History of posterior reversible encephalopathy syndrome
- •Planned surgery within 4 weeks post last dose
- •Moderate to severe proteinuria as demonstrated by urine dipstick for proteinuria ≥2+. For patients with ≥2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined, or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible
- •Requiring therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anticoagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed
- •Not recovered below National Cancer Institute-Common Terminology for Adverse Events (NCI-CTCAE) grade 1 or baseline from AEs due to previous therapy (patient with ≤ Grade 2 neuropathy or alopecia may be eligible)
- •Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy within 2 weeks prior to the baseline visit
- •Undergone major surgery requiring general anaesthesia or a respiratory assistance device within 4 weeks prior to the baseline visit (within 2 weeks for video-assisted thoracoscopic surgery [VATS] or open-and-closed [ONC] surgery)
- •Treated with other investigational drugs within 4 weeks prior to the baseline visit for this study
- •Pregnant* or lactating females, and females/males of childbearing potential who do not agree to a reliable and adequate method of contraception
- •A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drugs
- •Unable to participate in the trial according to the investigator's decision
- •Previous therapy with vascular endothelial growth factor (VEGF)-targeted agents including (but not limited to) bevacizumab
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher irAE
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
- •Known human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
- •Known active hepatitis B or hepatitis C infection. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
- •Have received a live vaccine within 30 days prior to enrollment. Seasonal flu vaccines that do not contain live virus are permitted
- •Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment
研究组 & 干预措施
TTAC-0001 and pembrolizumab
Experimental
TTAC-0001 and pembrolizumab combination therapy will be administered.
干预措施: TTAC-0001 and pembrolizumab combination (Drug)
结局指标
主要结局
Dose limiting toxicities
时间窗: During the first cycle (every cycle is 21 days) of treatment
The frequency and percentage of DLT will be presented by dose level
Immunogenicity
时间窗: From screening visit to end of treatment visit (time of progressive disease or 2 years)
Presence anti-drug antibody (ADA) will be listed
Adverse events
时间窗: From the screening visit to the end of treatment visit (time of progressive disease or 2 years)
The frequency and percentage of AEs will be presented by dose level
次要结局
- Overall response rate(At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days))
- Progression free survival(From screening visit to end of treatment visit (time of progressive disease or 2 years))
- Disease control rate(At every 2nd cycles until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years (every cycle is 21 days))
- Overall survival(From screening visit to date of patient's death (assessed up to 2 year after end of treatment visit))
研究者
研究点 (2)
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