BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy

Early Triple Negative Breast Cancer Clinical Trial

Official title:

Identification of BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01672671
• Other study ID #: TNNP 001
• Secondary ID: TNNP 001
• Status: Completed
• Phase: Phase 2
• First received: August 16, 2012
• Last updated: November 1, 2015
• Start date: August 2011
• Est. completion date: November 2015

Study information

• Verified date: November 2015
• Source: Russian Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess efficacy of platinum-based neoadjuvant chemotherapy in correlation with BRCA1-associated DNA repair dysfunction in patients with early triple negative breast cancer.

Description:

Recent gene expression profiling of breast cancer has identified specific subtypes with clinical, biologic, and therapeutic implications. The basal-like group of tumors is associated with aggressive behavior and poor prognosis, and typically do not express hormone receptors or HER-2 ("triple-negative" phenotype). Therefore, patients with basal-like cancers do not benefit from currently available targeted systemic therapy.

There is a lot of evidence about a link between basal-like breast cancer and BRCA1 deficiency. Many clinical characteristics and molecular features are shared by basal-like breast cancers and tumors that arise in carriers of BRCA1 germline mutations.

Some studies have indicated that BRCA1 mRNA expression was lower in basal-like sporadic cancers than in controls matched for age and grade. BRCA1 is rarely mutated in sporadic breast cancers and, therefore, it is believed that this may be a result of epigenetic mechanisms such as acquired methylation of the BRCA1 gene promoter or a dysfunction in the pathways that regulate BRCA1 expression, such as overexpression of ID4. The profound similarities between hereditary BRCA1-related breast tumors and basal-like tumors strongly implicate a fundamental defect in the BRCA1 or associated DNA-repair pathways (p53, PTEN) in sporadic basal-like tumors.

There is increasing evidence that the BRCA1-related DNA-repair defects, especially defective homologous recombination, determines sensitivity to certain agents, such as platinum salts-based chemotherapy. The complexity in downregulation of BRCA1 expression suggests that these approaches may only be effective in the treatment of a subset of sporadic basal-like cancers. Identification of specific markers for these cancers will be essential to translate an understanding of defective DNA repair into targeted treatments for this poor prognosis subtype.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: November 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Female patients, age =18 years=75;

2. Histologically confirmed invasive ER-, PR-, and HER2-negative (triple- negative) adenocarcinoma of the breast;

3. Clinical stage T1-2, N0-1, M0.

Exclusion Criteria:

1. Previous treatment for this breast cancer

2. History of malignancy treated with curative intent within the previous 5 years with the exception of skin cancer, cervical carcinoma in situ, or follicular thyroid cancer. Patients with previous invasive cancers (including breast cancer) are eligible if the treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease

3. Pregnancy or breast-feeding

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Early Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Doxorubicin, Paclitaxel, Cisplatin
Doxorubicin 25 mg/m2, IV weekly. Number of Cycles: 8 Paclitaxel 100 mg/m2, IV weekly. Number of Cycles: 8. Cisplatin 30 mg/m2, IV weekly. Number of Cycles: 8.

Locations

Country	Name	City	State
Russian Federation	Russian Cancer Research Center named after N.N.Blokhin RAMS	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Russian Academy of Medical Sciences

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients with 3/4 Grade CTC adverse events to assess toxicity and tolerability of the chemotherapy regimen		after 8 weeks of neadjuvant chemotherapy	Yes
Primary	The pathological complete response rate to neoadjuvant platinum-based chemotherapy	Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature.	after 8 weeks of neoadjuvant chemotherapy	No
Secondary	Disease-free survival		3 years	No
Secondary	Clinical responses to neadjuvant chemotherapy		after 8 weeks of neoadjuvant chemotherapy	No

External Links

•   Breast Cancer, Neoadjuvant Chemotherapy
•   Doxorubicin, Paclitaxel, Cisplatin