跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT03499353
NCT03499353终止2 期

A PHASE 2, NON RANDOMIZED, OPEN LABEL, SINGLE ARM, MULTI CENTER STUDY OF TALAZOPARIB FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER

Pfizer68 个研究点 分布在 1 个国家目标入组 61 人开始时间: 2018年8月27日最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
终止
发起方
Pfizer
入组人数
61
试验地点
68
主要终点
Percentage of Participants Achieving Pathological Complete Response (pCR) as Per Independent Central Review (ICR) in Evaluable Analysis Set as Per ICR With 80% Confidence Interval (CI)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

A PHASE 2, NON RANDOMIZED, OPEN LABEL, SINGLE ARM, MULTI CENTER STUDY OF TALAZOPARIB FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER

详细描述

TALAZOPARIB (PARP INHIBITOR) FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER. THIS IS A MONOTHERAPY TREATMENT FOR 24 WKS FOLLOWED BY SURGERY TO EVALUATE PATHOLOGICAL COMPLETE RESPONSE.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Single Group
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

  • •Germline BRCA 1/2 Mutation Positive
  • •Women and men at least 18 years of age or older.
  • •Histologically confirmed invasive adenocarcinoma of the breast
  • •HER2 negative breast cancer as defined by ASCO-CAP criteria
  • •Tumor greater than or equal toT1, N0-3
  • •No evidence of distant metastasis
  • •Adequate bone marrow, hepatic, and renal function
  • •ECOG performance status 0 or 1

排除标准

  • •Any other previous antitumor therapies for the current cancer event. Treatment for ductal carcinoma in situ (DCIS) is allowed; ie, surgery, hormonal therapy and radiation.
  • •Evidence of distant metastasis apparent prior to randomization
  • •Patients with inflammatory breast carcinoma
  • •Malignancy within the last 3 years, except: Stage 1 melanoma which does not require any further treatment after adequate surgical excision; adequately treated non melanoma skin cancer; Curatively treated in situ cancer of the cervix; Stage 1, Grade 1 endometrial carcinoma; or Adequately treated contralateral breast carcinoma which has been disease free for a year; Other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for 5 years.
  • •Previous or concomitant systemic anti cancer therapies used for the treatment of cancer in the last 3 years.
  • •Prior treatment with a PARP inhibitor in any disease setting
  • •Concomitant use of Strong P gp inhibitors or inducers or BCRP inhibitors
  • •Patients who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol
  • •Major surgery within 14 days prior to study entry
  • •Known history of cardiac disease, for example : Myocardial infarction or symptomatic cardiac ischemia within 24 weeks before screening; Congestive heart failure New York Heart Association Class III or IV; History of clinically significant ventricular arrhythmias within one year prior to randomization; History of Mobitz II second degree or third degree heart block, uncontrolled hypertension.
  • •Active clinically significant infection
  • •Clinically significant bleeding diathesis or coagulopathy
  • •Non healing wound, ulcer or bone fracture
  • •Known hypersensitivity to any of the components of talazoparib
  • •Patients with myelodysplastic syndrome/acute myeloid leukemia
  • •Patients with uncontrolled seizures.
  • •Any evidence of other disease or any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment

研究组 & 干预措施

TALAZOPARIB

Experimental

SINGLE ARM, NON-RANDOMIZED

干预措施: TALAZOPARIB (Drug)

结局指标

主要结局

Percentage of Participants Achieving Pathological Complete Response (pCR) as Per Independent Central Review (ICR) in Evaluable Analysis Set as Per ICR With 80% Confidence Interval (CI)

时间窗: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current American Joint Committee on Cancer \[AJCC\] staging system). pCR rate by ICR was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

Percentage of Participants Achieving pCR as Per ICR in Evaluable Analysis Set as Per ICR With 95% CI

时间窗: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib)

pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

次要结局

  • Percentage of Participants Achieving pCR as Per Investigator in Evaluable Analysis Set as Per Investigator(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants Achieving pCR as Per Investigator in ITT Analysis Set(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants Achieving pCR in Breast Only as Per Investigator in Evaluable Analysis Set as Per Investigator(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants Achieving pCR as Per ICR in Intention-to-Treat (ITT) Analysis Set With 80% CI(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants Achieving pCR as Per ICR in ITT Analysis Set With 95% CI(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants Achieving pCR in Breast Only as Per Investigator in ITT Analysis Set(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants Achieving pCR in Breast Only as Per ICR in Evaluable Analysis Set as Per ICR(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants Achieving pCR in Breast Only as Per ICR in ITT Analysis Set(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants With Residual Cander Burden (RCB) as Per ICR in Evaluable Analysis Set as Per ICR(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Percentage of Participants With RCB as Per ICR in ITT Analysis Set(Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib))
  • Probability of Being Event-Free at 3 Years in Evaluable Analysis Set(3 years after surgery)
  • Probability of Being Alive at 3 Years in Evaluable Analysis Set(3 years after first dose of talazoparib)
  • Probability of Being Alive at 3 Years in ITT Analysis Set(3 years after first dose of talazoparib)
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Trough Plasma Concentration (Ctrough) of Talazoparib in Cycles 2, 3 and 4 in PK Analysis Set(Pre-dose on Day 1 of Cycles 2, 3, 4)
  • Number of Participants With Serious Adverse Events (SAEs)(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Drug(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Number of Participants With TEAEs Leading to Temporary Discontinuation of Study Drug(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Number of Participants With TEAEs Leading to Dose Reduction of Study Drug(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Number of Participants With Laboratory Abnormalities(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Number of Participants With Hematology Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Number of Participants With Chemistry Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline(Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months))
  • Within-Participant Average Ctrough of Talazoparib at Steady State in PK Analysis Set(Pre-dose on Day 1 of Cycles 2, 3, 4)
  • Ctrough of Talazoparib in Cycles 2, 3 and 4 in Dose-Compliant PK Analysis Set(Pre-dose on Day 1 of Cycles 2, 3, 4)
  • Within-Participant Average Ctrough of Talazoparib at Steady State in Dose-Compliant PK Analysis Set(Pre-dosing on Day 1 of Cycles 2, 3, 4)
  • Number of Participants Who Achieved Definitive Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Per European Organization For Research And Treatment Of Cancer Quality Of Life Questionnaire (EORTC QLQ-30)(Baseline to End of Treatment visit (assessed for maximum of 33 weeks))
  • Kaplan-Meier Estimate of Time to Definitive Deterioration in GHS/QoL Per EORTC QLQ-30(Baseline to End of Treatment visit (assessed for maximum of 33 weeks))
  • Probability of Not Achieving Definitive Deterioration in GHS/QoL Per EORTC QLQ-C30 at 3 and 6 Months(3 months and 6 months post-baseline)
  • Number of Participants Who Achieved Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30(Baseline to End of Treatment visit (assessed for maximum of 33 weeks))
  • Kaplan-Meier Estimate of Time to Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30(Baseline to End of Treatment visit (assessed for maximum of 33 weeks))
  • Probability of Not Achieving Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30 at 3 and 6 Months(3 months and 6 months post-baseline)
  • Change From Baseline in Global QoL Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Physical Functioning Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Role Functioning Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Emotional Functioning Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Cognitive Functioning Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Social Functioning Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Fatigue Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Nausea and Vomiting Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Pain Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Dyspnoea Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Insomnia Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Appetite Loss Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Constipation Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Diarrhea Symptoms Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Financial Difficulties Per EORTC QLQ-C30(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Body Image Per EORTC QLQ Breast Cancer Quality of Life Questionnaire (EORTC QLQ-BR23)(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Sexual Functioning Per EORTC QLQ-BR23(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Sexual Enjoyment Per EORTC QLQ-BR23(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Future Perspective Per EORTC QLQ-BR23(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Systemic Therapy Side Effects Per EORTC QLQ-BR23(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Breast Symptoms Per EORTC QLQ-BR23(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Arm Symptoms Per EORTC QLQ-BR23(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Change From Baseline in Upset by Hair Loss Per EORTC QLQ-BR23(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Number of Participants With Deterioration in Nausea/Vomiting Symptoms(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Number of Participants With Improvement in Nausea/Vomiting Symptoms(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Number of Participants With No Change in Nausea/Vomiting Symptoms(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))
  • Number of Participants With Missed Expected Menstrual Periods Per Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks))

研究者

发起方
Pfizer
申办方类型
Industry
责任方
Sponsor

研究点 (68)

Loading locations...

相似试验

招募中
2 期
Efficacy of Talazoparib in Asian Metastatic Breast Cancer Patients With a Homologous Recombinant Deficiency (HRD) SignatureHRD 100 Gene Expression HighTriple Negative Breast Cancer
NCT05288127University of Malaya55
尚未招募
不适用
A randomized phase II clinical trial of talazoparib maintenance therapy in triple-negative breast cancer patients who showed platinum-sensitivity on first- or second-line platinum-based chemotherapy
KCT0005671Yonsei University Health System, Severance Hospital206
招募中
2 期
Olaparib in PALB2 Advanced Pancreatic CancerAdvanced Pancreatic CancerMetastatic Pancreatic Cancer
NCT06078787Azienda Ospedaliero-Universitaria di Modena16
撤回
2 期
A Study Evaluating Talazoparib in Relapsed Ovarian, Fallopian Tube, and Peritoneal CancerOvarian Cancer
NCT02836028Pfizer
已完成
2 期
Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor StatusRelapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
NCT02983799AstraZeneca272