NCT02032823进行中（未招募）3 期
A Randomised, Double-blind, Parallel Group, Placebo-controlled Multi-centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients With gBRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,837
- 试验地点
- 689
- 主要终点
- Invasive Disease Free Survival (IDFS)
研究概览
简要总结
Olaparib treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy
详细描述
Patients will be randomised in 1:1 ratio to either olaparib or placebo. Randomisation will be stratified by Hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC), prior neoadjuvant versus adjuvant chemotherapy and prior platinum use for breast cancer.
Randomised patients will receive study treatment for up to a maximum of 12 months. All patients will have safety assessments every 2 weeks during the first month, every 4 weeks for the following 5 months and 3 monthly for the remaining 6 months of study treatment plus 30 days after its discontinuation. Following randomisation, all patients will be assessed regularly for signs, symptoms and evidence of disease recurrence by taking medical history, physical examination and mammogram/breast MRI. Efficacy assessments will be performed on a 3 monthly basis during the first 2 years, followed by 6 monthly assessments for years 3, 4 and 5 and annually thereafter. All patients (except those with bilateral mastectomy) will have mammogram / breast MRI annually for 10 years beginning 6 months after randomisation.
All randomised patients will have clinical assessment visits for 10 years following their randomisation into the study. Once a patient completes 10 years of clinical assessment they will enter the survival follow up phase of the trial which will continue until approximately 10 years after the last patient is randomised.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the following phenotypes:
- •Triple negative breast cancer defined as: ER and PgR negative AND HER2 negative (not eligible for anti-HER2 therapy)
- •ER and/or PgR positive, HER2 negative
- •Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
- •Completed adequate breast and axilla surgery.
- •Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed.
- •ECOG 0-1.
排除标准
- •Any previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the excipients of study treatment.
- •Patients with second primary malignancy. EXCEPTIONS are:
- •adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma
- •other solid tumours and lymphomas (without bone marrow involvement) diagnosed ≥ 5 years prior to randomisation and treated with no evidence of disease recurrence and for whom no more than one line of chemotherapy was applied.
- •Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
- •Evidence of metastatic breast cancer
研究组 & 干预措施
Placebo
Placebo Comparator
Placebo tablets b.i.d. p.o.
干预措施: Placebo (Drug)
Olaparib
Experimental
Olaparib tablets 300mg b.i.d. p.o.
干预措施: Olaparib (Drug)
结局指标
主要结局
Invasive Disease Free Survival (IDFS)
时间窗: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)
An IDFS event is defined as the first occurrence of loco-regional or distant recurrence or new cancer or death from any cause.
次要结局
- Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy(6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021))
- Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy(6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021))
- Distant Disease Free Survival (DDFS)(From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months))
- Overall Survival (OS)(From date of randomisation to data cut off: 12 July 2021 (approximately 7 years 3 months))
- Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy(6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021))
- Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy(6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021))
- Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer(From date of randomisation to data cut off: 05 June 2024 (approximately 10 years 2 months))
研究者
研究点 (689)
Loading locations...
相似试验
已完成
2 期
Olaparib After Response to Trabectedin-pegylated Liposomal Doxorubicin in Recurrent Ovarian CarcinomaOvarian CancerNCT03470805Grupo Español de Investigación en Cáncer de Ovario9
进行中（未招募）
3 期
Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.Newly DiagnosedAdvanced Ovarian CancerFIGO Stage III-IVBRCA MutationComplete ResponsePartial ResponseFirst Line Platinum ChemotherapyNCT01844986AstraZeneca450
招募中
2 期
Olaparib Maintenance Therapy in Metastatic Breast CancerMetastatic Breast CancerNCT05629429National Taiwan University Hospital300
进行中（未招募）
1 期
Trial comparing weekly chemotherapy with oral olaparib or olaparib and cediranib in women with relapsed ovarian cancer.BRCA mutated platinum-resistant ovarian cancerMedDRA version: 21.1Level: LLTClassification code 10033131Term: Ovarian carcinomaSystem Organ Class: 100000004864EUCTR2016-000559-28-GBniversity of Oxford138
招募中
2 期
Olaparib With Cediranib or AZD6738 for the Treatment of Advanced or Metastatic Germline BRCA Mutated Breast CancerAdvanced Breast CarcinomaAnatomic Stage III Breast Cancer AJCC v8Anatomic Stage IIIA Breast Cancer AJCC v8Anatomic Stage IIIB Breast Cancer AJCC v8Anatomic Stage IIIC Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Germline BRCA1 Gene MutationGermline BRCA2 Gene MutationHER2/Neu NegativeMetastatic Breast CarcinomaPrognostic Stage III Breast Cancer AJCC v8Prognostic Stage IIIA Breast Cancer AJCC v8Prognostic Stage IIIB Breast Cancer AJCC v8Prognostic Stage IIIC Breast Cancer AJCC v8Prognostic Stage IV Breast Cancer AJCC v8NCT04090567M.D. Anderson Cancer Center60
相关资讯
Major Advances in Breast Cancer Treatment Highlighted in 2024• Inavolisib, combined with palbociclib and fulvestrant, received FDA approval for HR+/HER2-, PIK3CA-mutated advanced breast cancer, offering a new targeted therapy option.
• Ribociclib was approved for adjuvant treatment of HR+/HER2- early breast cancer with high recurrence risk, based on improved invasive disease-free survival in the NATALEE trial.
• Olaparib demonstrated a significant overall survival benefit in BRCA-mutated, HER2-negative early breast cancer, marking the first PARP inhibitor to achieve this milestone.
• Fam-trastuzumab deruxtecan-nxki (T-DXd) showed statistically significant progression-free survival improvement in HR+/HER2-low metastatic breast cancer after endocrine therapy.last yearSABCS 2024: Key Advances in Breast Cancer Treatment Highlighted• Patritumab deruxtecan shows sustained responses with fewer toxicities compared to chemotherapy in neoadjuvant treatment for early breast cancer.
• Olaparib demonstrates long-term efficacy in patients with HER2-negative, high-risk breast cancer harboring BRCA1/2 mutations, improving invasive and distant disease-free survival.
• Fam-trastuzumab deruxtecan-nxki (T-DXd) improves progression-free survival compared to physician's choice of therapy in HR-positive, HER2-low metastatic breast cancer.
• Immediate surgery reduces local recurrence in elderly breast cancer patients, while active monitoring proves non-inferior to standard treatment in low-risk DCIS.last yearSABCS 2024: Key Clinical Trials Highlight Advances in Breast Cancer Treatment• The EMBER3 trial suggests combining imlunestrant with abemaciclib could be more effective than imlunestrant alone for advanced ER-positive, HER2-negative breast cancer.
• PATINA trial results indicate that adding palbociclib to anti-HER2 therapy and endocrine therapy significantly improves progression-free survival in HR-positive, HER2-positive metastatic breast cancer.
• OlympiA trial update shows olaparib as adjuvant therapy reduces the risk of death by 28% in patients with germline BRCA1/2 mutations and high-risk HER2-negative breast cancer.
• SOLTI-VALENTINE study supports HER3-DXd's effectiveness in early breast cancer, demonstrating similar response rates to chemotherapy with fewer severe adverse events.2 years ago