Phase Ib/IIa Trial of Single Protein Encapsulated Doxorubicin, SPEDOX-6 in Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 67
- 试验地点
- 2
- 主要终点
- Overall Response Rate (ORR) by RECIST v1.1
研究概览
简要总结
This is a Phase 1b/IIa dose escalation clinical trial determining the recommended phase II dose of SPEDOX-6 in subjects with advanced, therapy-refractory soft-tissue sarcoma (STS); triple-negative breast cancer (TNBC); Non-small cell lung cancer (NSCLC); cervical cancer; ovarian cancer; KRAS mutant pancreatic ductal adenocarcinoma. These are subjects who have not previously been treated with anthracyclines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Subjects ≥ 18 years at the first screening examination/visit.
- •Subjects with advanced histologically or cytologically confirmed solid tumors (see below) refractory to or relapse from at least two previous therapies.
- •Tumor types expected to express lower levels of FcRn relative to normal tissue including: STS, TNBC, cervical cancer, NSCLC, ovarian cancer, and KRAS mutated pancreatic ductal adenocarcinoma without requirement for testing FcRn level.
- •Disease that is considered measurable by RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy of at least 12 weeks.
- •Human Immunodeficiency Virus (HIV)-positive trial participants should be on established antiretroviral therapy (ART) for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
- •Left ventricular ejection fraction > 50%.
- •Adequate organ function: (Hb ≥10 g/dL, ANC ≥1,000/µL3, and platelets
- •≥100,000/µL3), serum bilirubin ≤.5x the institutional upper limit of normal (ULN) (unless known Gilbert's disease), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤3x ULN, and creatinine clearance >50 mL/min as assessed by Cockcroft-Gault equation.
- •For patients with known Gilbert's disease, serum unconjugated bilirubin must be < 4 mg/dL.
- •Patient must have washed out of prior chemotherapy (at least 3 weeks from last end of therapy), radiotherapy (at least 4 weeks from last end of therapy), immunotherapy (at least 4 weeks from last end of therapy), other targeted therapies (at least 4 weeks from last end of therapy), or surgery (at least 4 weeks).
- •Recovery from toxicities of prior therapy. Toxicities should have recovered to CTCAE grade ≤ 1 or baseline with exception of alopecia.
- •Females of reproductive potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment. Additionally, female subjects of reproductive potential should agree to use effective acceptable forms of contraception: surgical sterilization (tubal ligation); total abstinence from sexual intercourse with the opposite sex; established hormonal birth control (e.g., oral, transdermal, injection, or implant) plus a barrier method or a double barrier method (intrauterine device, spermicide, or a diaphragm plus condom) for at least 1 month prior to Cycle 1 Day 1 and agreement to use such a method during study participation and for an additional 6 months after the last dose of SPEDOX-
- •For males of reproductive potential: vasectomy or highly effective contraception (e.g., condoms, abstinence) during the study and for an additional 6 months after the last dose of SPEDOX-6.
排除标准
- •Patients with cancers with known driver mutations for which there are known and effective targeted therapies that have not received those therapies, but are able to. If a patient has received appropriate targeted treatment for their mutations and progressed, or those treatments are contraindicated, they will be considered potentially eligible.
- •Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months before study entry.
- •Untreated metastases to the Central Nervous System (CNS).
- •Have received any prior doxorubicin or anthracycline equivalent.
- •Previous radiation to the mediastinal or pericardial area.
- •A known allergy to albumin.
- •HIV infection with CD4+ count < 350 cells/µL or Acquired Immunodeficiency (AIDS)-defining opportunistic infection in previous 12 months.
- •Pregnant (positive serum or urine pregnancy test) or lactating.
- •Previous treatment with an investigational agent or the non-approved use of a drug or device withing 4 weeks of study entry.
- •Uncontrolled diabetes mellitus.
- •Patients who require concomitant use of strong inhibitors or inducers of CYP3A4, CYP2D6 or P-glycoprotein (P-gp).
研究组 & 干预措施
Phase 1b Dose Level 2 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 40 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Pegfilgrastim (Drug)
Phase 1b Dose Level 2 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 40 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Filgrastim (Drug)
Phase 1b Dose Level 3 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 80 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Pegfilgrastim (Drug)
Phase 1b Dose Level 3 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 80 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Filgrastim (Drug)
Phase 1b Dose Level 3 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 80 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Spedox-6 (Drug)
Phase 1b Dose Level 1 - Spedox-6
Spedox-6, 20 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
干预措施: Spedox-6 (Drug)
Phase 1b Dose Level 2 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 40 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Spedox-6 (Drug)
Phase 1b Dose Level 4 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 120 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Pegfilgrastim (Drug)
Phase 1b Dose Level 4 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 120 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Filgrastim (Drug)
Phase 1b Dose Level 5 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 160 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Pegfilgrastim (Drug)
Phase 1b Dose Level 5 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 160 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Filgrastim (Drug)
Phase 1b Dose Level 6 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 200 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Pegfilgrastim (Drug)
Phase 1b Dose Level 6 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 200 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Filgrastim (Drug)
Phase 1b Dose Level 7 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 250 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Pegfilgrastim (Drug)
Phase 1b Dose Level 7 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 250 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Filgrastim (Drug)
Phase 1b Dose Level 8 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 310 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Pegfilgrastim (Drug)
Phase 1b Dose Level 8 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 310 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Filgrastim (Drug)
Phase 1b Dose Level 8 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 310 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Spedox-6 (Drug)
Phase 1b Dose Level 4 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 120 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Spedox-6 (Drug)
Phase 1b Dose Level 5 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 160 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Spedox-6 (Drug)
Phase 1b Dose Level 6 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 200 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Spedox-6 (Drug)
Phase 1b Dose Level 7 - Spedox-6 + Filgrastim/Pegfilgrastim
Spedox-6, 250 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.
干预措施: Spedox-6 (Drug)
结局指标
主要结局
Overall Response Rate (ORR) by RECIST v1.1
时间窗: 2 Years
Sum of Complete Response (CR) and Partial Response (PR) by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR
Disease Control Rate (DCR) by RECIST v1.1
时间窗: 2 Years
Disease Control Rate (DCR) defined as Sum of Stable Disease (SD) + Partial Response (PR) + Complete Response (CR) by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD is defined as an increase of at least 20% in the sum of the longest diameters of the target lesions, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. Stable Disease (SD) is defined as a tumor that has neither shrunk sufficiently to qualify as a partial response (PR) nor increased sufficiently to qualify as progressive disease (PD).
Complete Response Rate by RECIST v1.1
时间窗: 2 years
Complete Response Rate assessed by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is defined as the disappearance of all target lesions.
Partial Response Rate by RECIST v1.1
时间窗: 2 years
Partial Response rate assessed by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions
次要结局
- Stable Disease Rate by RECIST v1.1(2 years)
- Percentage of Responders by RECIST v1.1(2 years)
- Overall Survival(2 years)
- Progression Free Survival(2 years)
- Number of Patients with Grade 3 non-hematological toxicities by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0(2 years)
- Number of patients with Grade 4 non-hematologic (non-laboratory) by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0(2 years)
- Number of patients with Grade 3 or Grade 4 febrile neutropenia by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0(2 years)
- Number of patients with Grade 3 Thrombocytopenia in Combination with Grade 3 or greater blood and lymphatic system disorder by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0(2 years)
- Number of patients with Grade 3 AST or ALT increase that is associated with a Grade 2 or greater Rise in Bilirubin by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0(2 years)
研究者
Warren Chow
Professor - Division of Hematology-Oncology, Department of Medicine, UCI School of Medicine
University of California, Irvine