Breast Cancer Clinical Trial
— SURVIVEOfficial title:
SURVIVE (Standard Surveillance vs. Intensive Surveillance in Early Breast Cancer) - a Partially Double-blinded, Multi-center, Randomized, Controlled Superiority Study
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.
Status | Recruiting |
Enrollment | 3500 |
Est. completion date | December 2035 |
Est. primary completion date | December 2035 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion Criteria: 1. Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures. 2. Unilateral or bilateral primary invasive carcinoma of the breast, confirmed histologically. 3. 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. 4. A complete resection of the primary tumor, with resection margins free of invasive carcinoma. 5. 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. 6. 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. 7. No current clinical evidence for distant metastases. 8. Females or males = 18 years and = 75 years of age. 9. Performance status = 1, Eastern Cooperative Oncology Group (ECOG) scale. 10. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: 1. 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). 2. 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. 3. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent. 4. Renal insufficiency with GFR < 30 mL/min. 5. Previous or concomitant cytotoxic or other systemic antineoplastic treatment that is not used for treating the primary breast cancer. |
Country | Name | City | State |
---|---|---|---|
Germany | University Hospital Ulm Gynecology/Obstetrics | Ulm |
Lead Sponsor | Collaborator |
---|---|
Prof. Wolfgang Janni | German Federal Ministry of Education and Research |
Germany,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Establishment of a Biobank for Translational Research Endpoint | A biobank will allow the storage of unused biomaterials from both, the Intensive Surveillance arm as well as the Standard Surveillance arm. These materials will be used for future retrospective studies. | 5 years | |
Primary | Overall Survival (OS) | 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. | 10 years | |
Primary | Overall Lead Time Effect | 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. | 5 years | |
Secondary | Invasive disease-free survival (IDFS) | IDFS is defined as time from randomization until first IDFS event, including any invasive ipsilateral, regional, contralateral, and distant disease recurrence, second primary tumors, or death from any cause as event; non-invasive, in-situ cancer events are excluded. If a patient has not had an event, IDFS is censored at the date of last adequate tumor assessment. | 10 years | |
Secondary | Distant disease-free survival (DDFS) | DDFS is defined as time from randomization until first DDFS event including metastasis, second primary tumors and death from any cause as event. If a patient has not had an event, DDFS is censored at the date of last adequate tumor assessment. | 10 years | |
Secondary | Distant recurrence-free survival (DRFS) | DRFS is defined as time from randomization until first DRFS event including metastasis and second primary tumors; death from any cause is not included as event. If a patient has not had an event, DRFS is censored at the date of last adequate tumor assessment. | 10 years | |
Secondary | Breast cancer specific survival (BCSS) | BCSS is defined as time from randomization until breast cancer associated death of the patient. If a patient is not known to have died, BCSS is censored at the date of last contact. If a patient has died for reasons not associated with breast cancer (by clinical assessment), BCSS is censored at the date of death. | 10 years | |
Secondary | Invasive breast cancer free survival (IBCFS) | IBCFS is defined as time from randomization until first IBCFS event, including any invasive ipsilateral, regional, contralateral and distant disease recurrence or death from any cause as event; non-invasive, in-situ cancer events are excluded. If a patient has not had an event, IBCFS is censored at the date of last adequate tumor assessment. | 10 years | |
Secondary | Overall Survival (OS) after 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. | 10 years | |
Secondary | Molecular to via Imaging verified Recurrence Lead Time in the Interventional arm | The Lead Time is defined as time from first molecular relapse to via imaging verified recurrence for all patients in the liquid-biopsy guided Intensive Surveillance arm for whom a via imaging verified recurrence is documented during the 5-year interventional period of the study. If a patient has a via imaging verified recurrence but no documented molecular relapse, the Lead Time for this patient is set to '0'. This secondary endpoint will be assessed for all markers in combination and, where applicable, for each marker separately. | 5 years | |
Secondary | Quality of life (QoL) with questionnaires: EORTC QLQ-C30 | QoL will be monitored in both groups using a questionnaire which is to be completed every 6 months (EORTC QLQ-C30) in the interventional phase (first five years) and once a year during the five years of follow-up. QoL data will be collected on paper or via a digital health application. | 10 years | |
Secondary | Quality of life (QoL) with questionnaires: PA-F12 | QoL will be monitored in both groups using a questionnaire which is to be completed every 6 months (PA-F12) in the interventional phase (first five years) and once a year during the five years of follow-up. QoL data will be collected on paper or via a digital health application. | 10 years | |
Secondary | Liquid biopsy sensitivity (CA27.29, CEA, CA125, CTC and ctDNA) | Sensitivity is defined as the proportion of all patients in the liquid-biopsy guided Intensive Surveillance arm with a recurrence as verified by imaging during the 5-year interventional period of the study that had a positive biomarker result (i.e., molecular relapse) within 36 months before the recurrence as verified by imaging occurred (or within 60 months before the recurrence as verified by imaging occurred if in the first 36 months at least once a year a positive biomarker is measured). | 5 years | |
Secondary | Liquid biopsy specificity (CA27.29, CEA, CA125, CTC and ctDNA) | Specificity is defined as the proportion of all patients in the liquid-biopsy guided Intensive Surveillance arm with no recurrence as verified by imaging during the 5-year interventional period of the study that had only negative biomarker results (i.e., no indication of molecular relapse) within 36 months before the end of the 5-year interventional period of the study. | 5 years | |
Secondary | Liquid Biopsy False-Positive Rate (CA27.29, CEA, CA125, CTC and ctDNA) | False-positive rate is defined as the proportion of all patients in the liquid-biopsy guided Intensive Surveillance arm with a positive biomarker result (i.e., molecular relapse) during the 5-year interventional period of the study that had no recurrence as verified by imaging within 36 months after first molecular relapse. | 5 years | |
Secondary | Liquid Biopsy False-Negative Rate (CA27.29, CEA, CA125, CTC and ctDNA) | False-negative rate is defined as the proportion of all patients in the liquid-biopsy guided Intensive Surveillance arm with only negative biomarker results (i.e., no indication of molecular relapse) that had a recurrence as verified by imaging during the 5-year interventional period of the study. | 5 years | |
Secondary | Rate of liquid biopsy positivity (CA27.29, CEA, CA125, CTC and ctDNA) | The overall rate of liquid biopsy positivity is defined as the proportion of all patients in the liquid-biopsy guided Intensive Surveillance arm that had at least one positive biomarker result (i.e., molecular relapse) during the 5-year interventional period of the study. | 5 years |
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