NCT03895684已完成1 期
Phase 1 Trial of the LSD1 Inhibitor SP-2577 (Seclidemstat) in Patients With Advanced Solid Tumors
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
- 23
- 试验地点
- 2
- 主要终点
- Safety and tolerability of SP-2577
研究概览
简要总结
Phase 1, open-label, non-randomized dose finding study of SP-2577 in patients with advanced solid tumors.
详细描述
Phase 1, open-label, non-randomized dose finding study of SP-2577 given as oral tablets in patients with advanced solid tumors in 28-day cycles. The study design is based on a Simon's 4B design without intrapatient dose escalation.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 12 years and weight ≥ 40 kg.
- •Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid malignancy that is either metastatic or unresectable. At time of enrollment, subjects must have progressed on, be intolerant of, refuse, or ineligible for, all available standard of care therapies.
- •Subjects must demonstrate measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, with the exception of castration-resistant prostate cancer (CRPC) who should have progression based on the PCWG 3.0 criteria
- •Karnofsky ≥70% for over ≥16 years old and Lansky ≥70% for under 16 years old, equivalent to Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
- •Willingness to provide tumor biopsies of assessible lesions on and off treatment (Dose expansion cohort only). Optional for patients <18 years of age.
- •Able to swallow and retain orally administered medication.
- •Patients must have normal organ and marrow function
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Subjects with Ewing Sarcoma. See NCT03600649, Protocol Number: SALA-002-EW
- •Subjects with primary central nervous system tumors
- •Patients who have not recovered to grade 1 or baseline from adverse events related to prior therapy excluding lymphopenia, alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3 (Version 5.0).
- •Patients who are receiving any other investigational agents.
- •Prior therapy with LSD1 targeted agents including monoamine oxidases for cancer therapy.
- •Prior systemic anti-cancer treatment (chemotherapy, biologic therapy [ie. small molecular inhibitors, monoclonal antibodies]) within 21 days prior to Cycle 1 Day
- •Prior therapy with immunotherapy such as a checkpoint inhibitor, cellular therapy or vaccine therapy within 28 days prior to Cycle 1 Day
- •Patients must have recovered from any immune-related adverse events to grade 1 or baseline and require ≤ 10 mg of prednisone equivalents daily. Patients with immune-related hypothyroidism and/or hypoadrenalism may enroll while on thyroid or hydrocortisone replacement therapy, respectively.
- •Prior small port palliative radiotherapy within 14 days or 42 days from definitive local control radiation (any dose greater than 50Gy).
- •Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks prior to enrollment. Second-line hormone therapies such as enzalutamide, abiraterone, or orteronel within 2 weeks prior to enrolment. Subjects with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists. Subjects with prostate cancer may also remain on low-dose prednisone or prednisolone up to 10 mg/day
- •Prior therapy with long acting myeloid growth factor within 14 days or 7 days from a short acting myeloid growth factor.
- •Participation in a prior investigational study within 30 days prior to Cycle 1 Day
- •Patients with progressive or symptomatic brain metastases. Patients with brain metastases may be included in this trial as long as the brain metastases have received definitive treatment and are stable (i.e., no evidence of progression). The brain metastases must be stable for a minimum of 6 weeks.
- •Patients must have discontinued anti-seizure medications and steroids, except for physiologic steroid dosing (≤10 mg/day of prednisone equivalents).
- •Patients currently receiving any of the following substances and cannot be discontinued 14 days prior to Cycle 1 Day 1: Moderate or strong inhibitors or inducers of major CYP isoenzymes, including grapefruit, grapefruit hybrids, pomelos, star-fruit, and Seville oranges; Moderate or strong inhibitors or inducers of major drug transporters; Substrates of CYP3A4/5 with a narrow therapeutic index
- •Uncontrolled concurrent illness including, but not limited to: ongoing or active infection; transfusion dependent thrombocytopenia or anemia; psychiatric illness/social situations that would limit compliance with study requirements
- •Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following: symptomatic congestive heart failure; Left Ventricular Ejection Fraction (LVEF) ≤ 50%; unstable angina pectoris or cardiac arrhythmia; baseline QTcF (Fridericia) ≥ 450 milliseconds; Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome
- •Any major surgery within 21 days prior to Cycle 1 Day
- •Pregnant and breastfeeding women
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
- •HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SP-
- •In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
研究组 & 干预措施
Sp-2577
Experimental
Twice-daily administration of oral SP-2577
干预措施: SP-2577 Seclidemstat (Drug)
结局指标
主要结局
Safety and tolerability of SP-2577
时间窗: From screening through at least 30 days after end of treatment, up to approximately 24 months
Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0
次要结局
- Determine the maximum tolerated dose of SP-2577(DLTs within the first cycle of therapy (up to 28 days))
- Efficacy parameter: duration of response of SP-2577(From start of treatment through at least 30 days after end of treatment, up to approximately 24 months)
- Characterization of pharmacokinetics of SP-2577 (area under the concentration time profile)(At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.)
- Characterization of pharmacokinetics of SP-2577 (half-life)(At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.)
- Characterization of pharmacokinetics of SP-2577 (maximum plasma concentration)(At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.)
- Characterization of pharmacokinetics of SP-2577 (clearance rate)(At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.)
- Characterization of pharmacokinetics of SP-2577 (volume of distribution)(At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.)
- Efficacy parameter: progression-free survival of SP-2577(From start of treatment through at least 30 days after end of treatment, up to approximately 24 months)
- Changes in serum hemoglobin F concentrations(At protocol defined time points from start of treatment through end of treatment, up to approximately 24 months)
- Efficacy parameter: overall response rate of SP-2577(From start of treatment through at least 30 days after end of treatment, up to approximately 24 months)
- Changes in the molecular signatures of the tumor(At protocol defined time points from start of treatment through end of treatment, up to approximately 24 months)
- Characterization of pharmacokinetics of SP-2577 (time to maximum plasma concentration)(At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.)
研究者
研究点 (2)
Loading locations...
相似试验
终止
1 期
SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's LymphomaAdult Grade III Lymphomatoid GranulomatosisExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueNodal Marginal Zone B-cell LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaSplenic Marginal Zone LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Hodgkin LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Small Lymphocytic LymphomaUnspecified Adult Solid Tumor, Protocol SpecificWaldenström MacroglobulinemiaNCT00101244National Cancer Institute (NCI)31
进行中（未招募）
1 期
Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related SarcomasMyxoid LiposarcomaSarcoma,Soft TissueDesmoplastic Small Round Cell TumorExtraskeletal Myxoid ChondrosarcomaAngiomatoid Fibrous HistiocytomaClear Cell SarcomaPrimary Pulmonary Myxoid SarcomaMyoepithelial TumorSclerosing Epithelioid FibrosarcomaFibromyxoid TumorEwing SarcomaNCT03600649Salarius Pharmaceuticals, LLC50
已完成
1 期
A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib or Venetoclax in Participants With R/R Hematologic MalignanciesAggressive B-Cell Non-Hodgkin's Lymphoma (NHL)Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)Mantle Cell Lymphoma (MCL)Richter's SyndromeT-cell LymphomaDiffuse Large B-cell Lymphoma (DLBCL)Marginal Zone LymphomaMyeloid MalignanciesAcute Myeloid Leukemia (AML)Chronic Myelomonocytic Leukemia (CMML)Myelodysplastic Syndrome (MDS)MDS/Myeloproliferative Neoplasm (MPN) Overlap SyndromeNCT05665530Prelude Therapeutics86
招募中
1 期
Seclidemstat and Azacitidine for the Treatment of Myelodysplastic Syndrome or Chronic Myelomonocytic LeukemiaChronic Myelomonocytic Leukemia-0Chronic Myelomonocytic Leukemia-1Chronic Myelomonocytic Leukemia-2Recurrent Chronic Myelomonocytic LeukemiaRecurrent Myelodysplastic SyndromeMyelodysplastic SyndromeNCT04734990M.D. Anderson Cancer Center44
进行中（未招募）
1 期
Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor With Oral Decitabine in Subjects With Solid TumorsSolid TumorNCT03875287Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins35