The Benefit of Surgery in Stage IV of Breast Cancer

NCT04697043 | Unknown DMC

• 1 other identifier: 964635
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment of Metastatic Breast Cancer is not usually considered curative. Recent retrospective studies have demonstrated that resection of the breast tumor in patients with primary metastatic breast cancer is associated with a significant improvement of the prognosis. In all these aforementioned studies, the decision to perform surgery could have been influenced by favorable prognostic factors, such as younger age, the presence of only one metastatic site, or good response to systemic therapy. To rule out the impact of potential confounders, most studies adjusted for age, tumor size, number and sites of metastases and hormone receptor status. In addition, some studies also adjusted for comorbidity or surgical margins. For example, in the study of Bafford et al., the benefit of surgery seemed confined to patients operated upon before diagnosis of metastatic disease and there was no survival advantage in patients who received an operation of the breast tumor after the diagnosis of the metastatic disease had taken place. This phenomenon was referred to as the stage migration bias. In a study by Leung et al., the benefit from surgery disappeared in the multivariate analysis when taking into account the use of chemotherapy. Finally, in a study by Cady et al. coding errors in the retrospectively collected dataset were found to explain part of the survival advantage. 4Therefore, this randomized controlled trial (RCT) has been initiated. In the literature, several retrospective studies noted that 35-60% of patients with metastatic cancer at the time of diagnosis received local treatment of primary lesions, which resulted in a positive impact on survival. However, an analysis of 16,023 patients presenting with stage IV disease and an intact primary tumor compared outcomes between patients having surgery of the primary tumor to negative margins or no surgery. In a multivariate analysis adjusting for known prognostic factors, surgery reduced the HR for death to 0.61 (95% CI = 0.58 to 0.65). Multiple other retrospective studies from single institutions, registries, and population-based cohorts have confirmed this initial observation, but it is uncertain whether these studies reflect a real benefit for surgery or consistent selection bias. Three prospective randomized trials are examining the role of surgery in patients presenting with stage IV disease and an intact primary tumor. While awaiting the results of these trials, it is not known precisely how or when to integrate such surgical management into a standard medical therapy for metastatic breast cancer or which patients, in particular, are most likely to benefit from such treatment. 1 The aim of this study is to investigate the effect of surgery of the primary tumor in breast cancer patients with distant metastatic disease at initial diagnosis. According to the controversies in previous studies design of a study with the least confounding factor to decrease the bias seems to be necessary.

Conditions

Breast Cancer Stage IV

Keywords

Surgery; Breast Cancer; Stage IV

Outcome Measures

Primary Outcomes (3)

• The number of participants with no more tumor in their body

  Patients get rid of cancer and no more tumor in their body, no grows of tumor size. Treatment effect

  from 6 months after surgery to 5 years

• PFS (progression free survival)

  Patients be alive with no cancer

  from 6 months after surgery to 5 years

• Overall Survival (OS)

  Patients survival

  from 6 months after surgery to 5 years

Secondary Outcomes (1)

• The number of participants with no more distant metastasis

  from 6 months after surgery to 5 years

Study Arms (2)

systemic therapy followed by surgery

EXPERIMENTAL

ُThe main intervention is surgery. After the diagnosis of primary distant metastatic breast cancer, patients will be randomly allocated into two groups: A. systemic therapy followed by surgery if the disease is not progressive; B. Systemic therapy Patient selection criteria The eligibility criteria for the study are: \- primary distant metastatic breast cancer (M1); - an anticipated survival of at least 6 months; - a histologically proven diagnosis of the breast tumor; - a known hormonal and HER2Neu status; - TNM classification: T1-T3, resectable T4 status, and N0-N3; - performance status and comorbidity should allow surgery and/or systemic therapy; - age ≥ 18 years;- written informed consent.

Procedure: Systemic therapy followed by surgery if the disease is not progressive

Systemic therapy

NO INTERVENTION

After the diagnosis of primary distant metastatic breast cancer, patients will be randomly allocated into two groups: A. systemic therapy followed by surgery if the disease is not progressive; B. Systemic therapy Patient selection criteria The eligibility criteria for the study are: \- primary distant metastatic breast cancer (M1); - an anticipated survival of at least 6 months; - a histologically proven diagnosis of the breast tumor; - a known hormonal and HER2Neu status; - TNM classification: T1-T3, resectable T4 status, and N0-N3; - performance status and comorbidity should allow surgery and/or systemic therapy; - age ≥ 18 years;- written informed consent.

Interventions

Systemic therapy followed by surgery if the disease is not progressive PROCEDURE

Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The systemic therapy followed by surgery if the disease is not progressive.

systemic therapy followed by surgery

Eligibility Criteria

• Age: 18 Years - 90 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary confirmed distant metastatic breast cancer (M1); A histologically proven diagnosis of the breast tumor; A known hormonal and HER2Neu status; Having TNM classification: T1-T3, resectable T4 status, and N0-N3; - performance status and comorbidity should allow surgery and/or systemic therapy; Accepting the surgery by written informed consent.

You may not qualify if:

• No confirmed primary invasive breast cancer in the medical history Having another malignancy within the last 10 years, besides basal cell carcinoma of the skin or early-stage cervical cancer Having the history of surgical treatment and/or radiotherapy of the breast tumor before randomization Having irresectable T4 breast tumor Having synchronous bilateral breast cancer.

Sponsors & Collaborators

• Tehran University of Medical Sciences: lead

Study Sites (1)

Tehran University of Medical Sciences

Tehran, 1136746911, Iran

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Centralized randomization will take place immediately after the diagnosis of primary distant metastatic breast cancer, using computer-generated randomization. dominant location of distant metastases (bone, soft tissue (lymph nodes and subcutaneous metastases) and visceral metastases), hormonal receptor status (ER and/ or PR positive or both negative) and HER2Neu status (overexpression yes or no) will be recorded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: January 6, 2021
• Study Start: November 20, 2020
• Primary Completion: November 20, 2021
• Study Completion: December 20, 2021
• Last Updated: January 6, 2021

Record last verified: 2020-12

Locations

IR (1)