ACTRN12613000198729进行中（未招募）1 期
A phase I study of the safety and immune effects of an escalating dose of autologous GD2 chimeric antigen receptor-expressing peripheral blood T cells in patients with GD2-positive metastatic melanoma and refractory solid tumours
Royal Adelaide Hospital Cancer Centre0 个研究点目标入组 12 人开始时间: 2013年2月19日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 12
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
- 分配方式
- Non-randomised trial
- 主要目的
- Treatment
- 盲法
- Open (masking not used)
入排标准
- 年龄范围
- 18 Years 至 o limit（—）
- 性别
- All
入选标准
- •1.At least 18 years old;
- •2.Histological diagnosis of small cell lung cancer, triple negative breast cancer, osteosarcoma, Ewing sarcoma, and such soft tissue sarcomas as rhabdomyosarcoma, liposarcoma, fibrosarcoma, synovial sarcoma, pleomorphic undifferentiated sarcoma, and desmoplastic small round cell tumours (DSRCT), or metastatic melanoma (surgically incurable and unresectable stage III or stage IV; AJCC Cancer Staging Manual, 7th edition, 2010) and greater than or equal to 10% GD2 positive cells (by an independent pathologist);
- •3.Unresectable stage III melanoma must have confirmation from a surgical oncologist. Melanoma will have V600 BRAF gene mutation status determined; V600E, K, R, or D mutations may be eligible for treatment with dabrafenib and trametinib;
- •4.Must have failed standard therapy;
- •5.For metastatic melanoma patients, who will not receive dabrafenib and trametinib concurrently with the GD2-iCAR-PBT infusion, standard therapy includes prior use of BRAF and/or MEK inhibitor for PBS-eligible BRAF-mutant melanoma, combination ipilimumab/nivolumab immunotherapy or pembrolizumab or nivolumab monotherapy. Patients who have not previously tolerated dabrafenib and/or trametinib in the adjuvant or metastatic setting are also eligible. Patients in whom re-induction with ipilimumab or pembrolizumab or nivolumab is contra-indicated because of grade 3 or 4 non-endocrine immune-related adverse events are also eligible;
- •6.Measurable disease by RECIST 1.1;
- •7.Must be able and willing to provide written informed consent;
- •8.Eastern Cooperative Oncology Group Performance Status of 0 or 1;
- •9.Recovered to = Grade 1 from the acute toxic effects of all prior anti-cancer treatment at least a week before entering this study; for prior ipilimumab, nivolumab, or pembrolizumab, the GD2-iCAR-PBT infusion is given 5 half-lives or greater than or equal to 70 days, greater than or equal to 133 days, or greater than or equal to 110 days after the last dose, respectively;
- •10.Life expectancy of greater than or equal to 12 weeks;
- •11.Availability of T-cell product that has met batch release criteria including greater than or equal to 20% expression of GD2-iCAR (by flow cytometry) on the autologous PBT;
- •12.Fertile male patients must use an effective method of contraception during treatment and for 4 months following discontinuation of trametinib in combination with dabrafenib, or for 4 weeks following discontinuation of dabrafenib;
- •13.Female patients are eligible to enter and participate in the study if they meet the following inclusion criteria:
- •Hysterectomised;
- •Bilateral oophorectomy (ovariectomy), or
- •Bilateral tubal ligation, or
- •Post-menopausal (demonstrated total cessation of menses for greater than or equal to 1 year).
- •For females of childbearing potential, the patient must:
- •Have a negative serum pregnancy test at screening, and a negative urine pregnancy test, prior to dosing at each treatment course.
- •The female patient must also agree to the use of the following contraceptive methods:
- •An intrauterine device (IUD) with a documented failure rate of less than 1% per year;
- •Vasectomized partner who is sterile prior to the patient’s entry and is the sole sexual partner for that woman;
- •Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm;
- •Complete abstinence from sexual intercourse
排除标准
- •1.Evidence of symptomatic CNS lesions as determined by investigator, use of steroids or anti-seizure medications for treatment of brain metastases. Patients with asymptomatic lesions previously irradiated or surgically resected that are radiologically stable are eligible. Patients with incidentally found brain metastasis that are asymptomatic and for which no treatment is planned are also eligible;
- •2.Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count less than or equal to 1.5 x 109/L or platelet count less than or equal to 100 x 109/L (can not be post-transfusion) or hemoglobin less than 90 g/L (can be post-transfusion);
- •3.Serum bilirubin > 1.5 times the upper limit of normal;
- •4.In absence of metastases, liver transaminase levels > 2.5 times the upper limit of normal;
- •5.If metastases are evident, liver transaminase levels > 5 times the upper limit of normal will be acceptable;
- •6.Creatinine clearance of less than or equal to 50mL/min calculated by Cockcroft-Gault;
- •7.Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. Patients must be able to swallow tablets;
- •8.Evidence of severe or uncontrolled systemic diseases (e.g., infection requiring treatment with intravenous (IV) antibiotics, unstable or uncompensated respiratory, cardiac [including life threatening arrhythmias], hepatic, or renal disease.
- •9.Unresolved toxicity greater than or equal to CTC Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor;
- •10.Presence of at least grade 2 peripheral neuropathy;
- •11.Participation in a trial of an investigational agent within the 30 days prior to day 0;
- •12.Pregnant or breast-feeding females;
- •13.Patients with an active seizure disorder;
- •14.History of congenital long QT syndrome, history or presence of clinically significant ventricular or atrial dysrhythmias greater than or equal to Grade 2 (NCI CTCAE Version 4.0);
- •15.Patients with a corrected QTc interval of greater than 450 ms (males) and 470 ms (females);
- •16.Evidence of active infection with HIV, hepatitis B, or hepatitis C;
- •17.Immunosuppressive therapy including corticosteroids within four weeks of screening;
- •18.Patients with a history of hypersensitivity reactions to murine protein-containing products, dabrafenib, trametinib, or another BRAF or MEK inhibitor;
- •19.Use of prophylactic low-dose aspirin, NSAIDs, anticoagulants (unless prescribed for venous or arterial thrombo-embolic disease or atrial fibrillation) will be prohibited in patients commencing dabrafenib and trametinib.
- •20.Patients with a tumour in a location where enlargement could cause airway obstruction;
- •21.Any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in this trial or which would jeopardise compliance with the protocol.
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