PHASE 2 STUDY OF SINGLE-AGENT PF-03084014 IN PATIENTS WITH ADVANCED TRIPLE-NEGATIVE BREAST CANCER WITH OR WITHOUT GENOMIC ALTERATIONS IN NOTCH RECEPTORS
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 19
- 试验地点
- 35
- 主要终点
- Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+)
研究概览
简要总结
This study is designed to evaluate the preliminary anti-tumor activity and tolerability of PF-03084014 when administered as a single agent in the treatment of patients with advanced triple receptor-negative breast cancer (mTNBC) harboring genomic alterations in Notch receptors (NA+), and in a smaller subset of mTNBC patients whose tumor tests negative for genomic alterations in Notch receptors (NA-)
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological diagnosis of triple negative breast cancer (TNBC) with evidence of a) metastatic or b) locally recurrent advanced disease that is not amenable to resection or radiotherapy with curative intent.
- •Availability of an original diagnostic tumor tissue or the most recent metastatic tumor biopsies (archival biopsy or de novo biopsy) and a peripheral blood sample for Notch receptors genomic profiling
排除标准
- •Known brain metastases.
- •Prior treatment with gamma secretase inhibitor or other Notch signaling inhibitor.
研究组 & 干预措施
PF-03084014
PF-03084014 will be administered orally, continuously, twice daily at 150 mg, but the dose can be reduced to 100 mg or 80 mg.
干预措施: PF-03084014 (Drug)
结局指标
主要结局
Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+)
时间窗: Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.
OR status based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis less than \[\<\]10 millimeter \[mm\]). PR: Greater than or equal to (\>=)30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.
次要结局
- Progression-Free Survival (PFS) in Participants With NA+ or NA mTNBC(2 years)
- Pharmacodynamic (PD) Effects of PF-03084014 in Tumor Specimens and Peripheral Blood(Day 1 of Cycle 1, 2, 3, and 5)
- Number of Participants With Laboratory Test (Urinalysis) Abnormalities(Day 1 of Cycle 1)
- Overall Survival (OS) in Participants With NA+ or NA mTNBC(2 years)
- Pre-dose Serum Concentration (Ctrough) for PF-03084014(Day 1 of Cycle 1, 2, 3, and 5)
- Alterations in Genes, Proteins, and RNAs Relevant to the Notch Signaling Pathway, to TNBC Biology, and to Sensitivity/Resistance to PF-03084014 in Tumor Specimens and Peripheral Blood.(Day 1 of Cycle 1, 2, 3, and 5)
- OR Rate in Participants With mTNBC Whose Tumors Tested Negative for Eenomic Alterations in Notch Receptor (NA-)(Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.)
- Duration of Response (DR) in Participants With NA+ or NA mTNBC(2 years)
- One-Year Survival Probability in Participants With NA+ or NA mTNBC(1 year)
- Type of Notch Genomic Alterations in Participants With NA+ mTNBC(2 years)
- Number of Notch Genomic Alterations in Participants With NA+ mTNBC(2 years)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)(2 years)
- Number of Participants With Treatment-Emergent AEs by CTCAE Grade(2 years)
- Number of Participants With Laboratory Test (Hematology) Abnormalities(Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles.)
- Number of Participants With Laboratory Test (Chemistry) Abnormalities(Day 1 and Day 15 of Cycles 1, 2, 3, 4, 5, and subsequent cycles up to Cycle 8 and Day 8 of Cycle 1)