SURVIVE (Standard Surveillance vs. Intensive Surveillance in Early Breast Cancer) - a Partially Double-blinded, Multi-center, Randomized, Controlled Superiority Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 3,500
- 试验地点
- 2
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The goal of this clinical study is to evaluate the potential benefits of intensified surveillance versus standard surveillance in medium-risk and high-risk early breast cancer patients.
The main questions it aims to answer are:
- Comparison of the 5-year ob´verall survival rates between patients in the Standard Surveillance arm versus patients in the liquid-biopsy guided Intensive Surveillance arm
- Determination of the Overall Lead Time Effect generated due to tumor marker/CTC/ctDNA guided Intensive Surveillance compared to Standard Surveillance after primary therapy in early breast cancer patients.
Participants will recieve regular blood drawals. Solely the blood samples of the intensive surveillance arm will be analysed for prospective tumor markers/CTCs/ctDNAs. Abnormal findings of either marker will trigger diagnostic imaging to search for possible metastases. The blood samples of the standard surveillance arm will solely be biobanked for future research purposes.
详细描述
This is a partially double-blinded, multi-center, randomized, controlled superiority study to evaluate the potential benefits of intensified surveillance versus standard surveillance in medium-risk and high-risk early breast cancer patients.
3500 patients will be enrolled after completion of primary anti-tumor therapy (adjuvant chemotherapy, surgery or radiotherapy, whichever occurs last) and randomized in a 1:1 ratio to receive:
- Standard Surveillance according to national guidelines or
- Intensive Surveillance with additional testing of blood samples for prospective tumor markers (CA27.29, CA125, CEA), CTC and ctDNA
In both study arms patients will receive standard surveillance according to national guidelines, including clinical follow-up visits every 3 months for the first 3 years and every 6 months for the following 2 years. Additionally, blood samples will be drawn and Quality of Life (QoL) will be analyzed at these clinical follow-up visits in both arms.
In the Standard Surveillance arm blood samples will be stored in a biobank. In the Intensive Surveillance arm blood samples will be tested for prospective tumor markers (CA27.29, CA125, CEA), CTCs and ctDNA. Abnormal findings of either marker (CA27.29 or CA125 or CEA or CTC or ctDNA) will trigger diagnostic imaging. Additionally, blood samples will be stored in a biobank for retrospective analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This study will be performed as partially double-blinded. This means, all patients and doctors are blinded initially as blood sampling is done in all patients, irrespective of randomization to the Standard Surveillance arm or the Intensive Surveillance arm. If one of the biomarkers (CA27.29, CEA, CA125, CTC, ctDNA) is abnormal and requires a confirmatory blood sampling or triggers imaging, unblinding is the consequence as these patients will be asked to undergo further assessments and the responsible doctor will arrange these. Unblinding in this case is the ethical consequence of not letting all patients undergo a confirmatory blood sampling or even undergo additional imaging without elevated biomarkers. If no confirmatory blood sampling or imaging is necessary, patients in the Intensive Surveillance arm will not be unblinded as there is no purpose to serve. Patients in the Standard Surveillance arm will not be unblinded altogether.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
- •Unilateral or bilateral primary invasive carcinoma of the breast, confirmed histologically.
- •Patients with intermediate- to high-risk early breast cancer defined as either
- •an indication for (neo-)adjuvant chemotherapy (regardless whether performed or not), and/or
- •Large tumor (> 50 mm), and/or
- •Positive lymph nodes, and/or
- •High grade (>= G3). Indication to (neo-)adjuvant chemotherapy is seen as stated in the German S3 guideline for breast cancer as well as stated in the guidelines from the AGO.
- •A complete resection of the primary tumor, with resection margins free of invasive carcinoma.
- •Completion of primary anti-tumor therapy (adjuvant chemotherapy, surgery or radiotherapy, whichever occurs last) at least 4 weeks but no more than 24 months previously. Enrollment of patients during any kind of adjuvant therapy except chemotherapy (e.g., but not limited to endocrine therapy, antibody therapy, CDK4/6-inhibitors, PARP inhibitors, PI3K inhibitors, antibody-drug conjugates and other novel agents) is allowed.
- •Availability of primary tumor tissue from core biopsy or surgical removed tissue (FFPE Slide (≥ 6 mm³, min. 10 slides, thickness: 5 µm-10 µm, area >150 mm² and 1 H&E stained slide, minimum 20% tumor content) or FFPE Block (≥ 6 mm³ thickness: 100 µm, area: >150 mm² and 1 H&E stained slide, minimum 20% tumor content) or Genomic DNA extracted from FFPE slides or block (≥ 600 ng, Minimum volume: 25 µL, concentration: 20 ng/µL, buffer: 10 mM Tris pH 8, 1 mM EDTA)) at timepoint of enrollment.
- •Patients with primary systemic therapy: tissue from core biopsy
- •Patients receiving surgery as primary therapy: surgically removed cancer tissue.
- •No current clinical evidence for distant metastases.
- •Females or males ≥ 18 years and ≤ 75 years of age.
- •Performance status ≤ 1, Eastern Cooperative Oncology Group (ECOG) scale.
- •Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
排除标准
- •Patients with a history of any secondary primary malignancy are ineligible with the following exceptions:
- •in situ carcinoma of the cervix or
- •adequately treated basal cell carcinoma of the skin or
- •ipsi- or contralateral non-invasive carcinoma of the breast (DCIS).
- •Patients in pregnancy or breastfeeding. If a patient gets pregnant during the participation in the interventional phase of the study (Year 1-5), an end of intervention visit will be scheduled and the patient will enter the follow-up phase of the study. Pregnancy during the follow-up phase of the study is to be reported but does not lead to an exclusion of the study.
- •History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
- •Renal insufficiency with GFR < 30 mL/min.
- •Previous or concomitant cytotoxic or other systemic antineoplastic treatment that is not used for treating the primary breast cancer.
结局指标
主要结局
Overall Survival (OS)
时间窗: 10 years
OS is defined as time from randomization until the death of the patient independent of cause of death. If a patient is not known to have died, OS is censored at the date of last contact.
Overall Lead Time Effect
时间窗: 5 years
This endpoint is a composite measure, defined as the median time from molecular to via Imaging verified Recurrence Lead Time (calculated only for patients in the liquid-biopsy guided Intensive Surveillance arm) + Difference in time to distant recurrence between the two arms (i.e., difference between median time from randomization to distant recurrence for all patients with distant recurrence in the Standard Surveillance arm and median time from randomization to distant recurrence for all patients with distant recurrence in the liquid-biopsy guided Intensive Surveillance arm). The Overall Lead Time Effect will be assessed for all markers in combination.
次要结局
- Distant recurrence-free survival (DRFS)(10 years)
- Invasive breast cancer free survival (IBCFS)(10 years)
- Overall Survival (OS) after 10 Years(10 years)
- Quality of life (QoL) with questionnaires: EORTC QLQ-C30(10 years)
- Invasive disease-free survival (IDFS)(10 years)
- Molecular to via Imaging verified Recurrence Lead Time in the Interventional arm(5 years)
- Quality of life (QoL) with questionnaires: PA-F12(10 years)
- Liquid biopsy sensitivity (CA27.29, CEA, CA125, CTC and ctDNA)(5 years)
- Distant disease-free survival (DDFS)(10 years)
- Liquid Biopsy False-Positive Rate (CA27.29, CEA, CA125, CTC and ctDNA)(5 years)
- Liquid Biopsy False-Negative Rate (CA27.29, CEA, CA125, CTC and ctDNA)(5 years)
- Breast cancer specific survival (BCSS)(10 years)
- Liquid biopsy specificity (CA27.29, CEA, CA125, CTC and ctDNA)(5 years)
- Rate of liquid biopsy positivity (CA27.29, CEA, CA125, CTC and ctDNA)(5 years)
研究者
Prof. Wolfgang Janni
Director of the clinic for gynecology and obstetrics
University of Ulm