Follow-up of Early Breast Cancer by Dynamic Evaluation of CEA and CA 15.3 Followed by 18FDG-PET

Three-monthly Dynamic Evaluation of CEA and CA 15.3 vs Usual Practice in the Follow-up of Early Breast Cancer Patients: a Randomized Study

The main purpose of follow-up in asymptomatic breast cancer patients during and after adjuvant treatment is to detect breast cancer recurrence and metastatic disease.The aim of this trial is to verify if, in asymptomatic patients, the serial measurement of serum CEA and CA 15.3, with diagnostic imaging procedures (18FDG-PET) performed only in case of a critical increase of serum CEA and CA 15.3 level, can anticipate the diagnosis of breast cancer local and distant recurrence compared to the usual follow-up practice.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Arm B, tumor markers assessment

• Study Type: Interventional
• Enrollment (Actual): 1507
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, SSD Oncologia Medica Addarii
  • Bolzano, Italy, 39100
    • Azienda Sanitaria dell'Alto Adige - Ospedale Centrale di Bolzano
  • Ferrara, Italy, 44124
    • Azienda Ospedaliero-Universitaria di Ferrara
  • Reggio Emilia, Italy, 42123
    • IRCCS Azienda Ospedaliera S. Maria Nuova di Reggio Emilia
  • Bolzano
    • Bressanone, Bolzano, Italy, 39042
      • Azienda Sanitaria dell'Alto Adige - Ospedale di Bressanone
    • Merano, Bolzano, Italy, 39012
      • Azienda Sanitaria dell'Alto Adige - Ospedale di Merano
  • Venezia
    • Mirano, Venezia, Italy, 30035
      • ASL13 - Presidio Ospedaliero Mirano, U.O.C. Oncologia ed Ematologia Oncologica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Male or female ≥18 years.
• Histologically confirmed stage I-III epithelial breast cancer.

• Adequate surgery of breast and axilla:

  1. patients must have undergone either a total mastectomy or breast conserving surgery
  2. surgical margins of the resected specimen must be histologically free of invasive tumor.
• Cohort 1: if chemotherapy and/or radiotherapy are indicated the patients must be randomized between 1 month and 2 months from the end of chemotherapy and/or radiotherapy; if only hormonal adjuvant therapy is indicated the patients must be randomized within 3 months from the completion of surgery
• Cohort 2: patients must be randomized in the trial after 5 years of follow-up without relapse (but within year 6)
• Signed informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

• Histologically confirmed stage 0 epithelial breast cancer (carcinoma in situ).
• Special histologies with a high or low risk of relapse (i.e. sarcoma and tubular carcinoma)
• T1a and T1b tumors with all the following characteristics: G1-2 and N0 and RE > 10%, RPg > 10% and HER2 negative and Ki67≤14%
• Evidence of distant metastases
• Patients participating to other clinical trials requiring follow-up not equal to standard
• Previous history of cancer within 5 years from randomization (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage I uterine cancer, or other non-breast malignancies with an outcome similar to those mentioned above)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Arm A, usual follow-up practice; Imaging studies and serum markers (CEA, CA 15.3, others) performed according to local practice
Experimental: Arm B, tumor markers assessment; Serum CEA and CA 15.3 performed every 3 months. No imaging studies allowed in asymptomatic patients: imaging studies (18 FDG-PET) performed only in case of critical increase of CEA and /or CA 15.3 serum levels (+100% for CEA and +75% for CA15.3), even if in the normal range.	Other: Arm B, tumor markers assessment; Tumor markers assessment every three months through the study or until disease recurrence; Other Names: CEA; CA15-3; 18FDG-PET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time interval between date of randomization and date of diagnosis of disease distant recurrence	Primary objective of the study is to verify if the experimental arm (serial measurement of serum CEA and CA 15.3 with diagnostic imaging procedures - i.e. 18FDG-PET- performed only in case of critical increase of serum markers level) can anticipate the diagnosis of breast cancer loco-regional (except for in-breast recurrence) or distant metastases compared to the control arm (usual follow-up practice).	Participants will be followed from date of randomization until the date of first documented disease distant recurrence or date of death from any cause, whichever came first, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predefined critical difference of CEA and CA15-3	Secondary objective is to evaluate the Positive Predictive Value (PPV) and the Negative Predictive Value (NPV) of CEA and CA15.3 dynamic changes in the diagnosis of breast cancer loco-regional (except for in-breast recurrence) or distant metastases.	Participants will be followed from date of randomization until the date of first documented disease distant recurrence or date of death from any cause, whichever came first, assessed up to 60 months
Exploratory analysis in the different subtypes	Secondary objective is to perform an exploratory analysis on diagnostic anticipation in the different subtypes (ER and HER2 status)	Participants will be followed from date of randomization until the date of first documented disease distant recurrence or date of death from any cause, whichever came first, assessed up to 60 months
Imaging diagnostic tests evaluation	Secondary objective is to measure how many imaging diagnostic tests will be avoided in the experimental arm compared to the control arm	Participants will be followed from date of randomization until the date of first documented disease distant recurrence or date of death from any cause, whichever came first, assessed up to 60 months
Patient quality of life evaluation	Secondary objective is to compare the quality of life in the two arms	Participants will be followed from date of randomization until the date of first documented disease distant recurrence or date of death from any cause, whichever came first, assessed up to 60 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Collaborators: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Azienda ULSS 12 Veneziana; PONS-S (Patientenorientierte Nachsorge-Stiftung), Augsburg, Germany
• Investigators: Principal Investigator: Claudio Zamagni, MD, Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Anticipated): November 1, 2026
• Study Completion (Anticipated): December 1, 2030

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Estimate): December 29, 2022
• Last Update Submitted That Met QC Criteria: December 28, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: breast cancer; follow-up; tumor markers
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: KRONOS; PONS-S Italy (Other Identifier: S.Orsola-Malpighi Hospital)