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

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

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Early Triple Negative Breast Cancer
Intervention	Drug: Doxorubicin, Paclitaxel, Cisplatin
Phase	Phase 2
Sponsor	Russian Academy of Medical Sciences
Responsible Party	Russian Academy of Medical Sciences
ClinicalTrials.gov Identifier	NCT01672671
First Received	August 16, 2012
Last Updated	May 21, 2013
Last verified	May 2013

Tracking Information[ + expand ][ + ]

First Received Date	August 16, 2012
Last Updated Date	May 21, 2013
Start Date	August 2011
Estimated Primary Completion Date	Not Provided
Current Primary Outcome Measures	The pathological complete response rate to neoadjuvant platinum-based chemotherapy [Time Frame: after 8 weeks of neoadjuvant chemotherapy] [Designated as safety issue: No]Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature.
Current Secondary Outcome Measures	Disease-free survival [Time Frame: 3 years] [Designated as safety issue: No] Clinical responses to neadjuvant chemotherapy [Time Frame: after 8 weeks of neoadjuvant chemotherapy] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy
Official Title	Identification of BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy
Brief 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.
Detailed 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.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Early Triple Negative Breast Cancer
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.
Study Arm (s)	Experimental: Neoadjuvant platinum-based chemotherapy Doxorubicin, Paclitaxel, Cisplatin

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	40
Estimated Completion Date	Not Provided
Estimated Primary Completion Date	January 2014
Eligibility Criteria	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
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Mona Frolova, PhD +74993241880 drfrolova@yandex.ru
Location Countries	Russian Federation

Administrative Information[ + expand ][ + ]

NCT Number	NCT01672671
Other Study ID Numbers	TNNP 001
Has Data Monitoring Committee	No
Information Provided By	Russian Academy of Medical Sciences
Study Sponsor	Russian Academy of Medical Sciences
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	May 2013

Locations[ + expand ][ + ]

Russian Cancer Research Center named after N.N.Blokhin RAMS	Moscow, Russian Federation, 115478 Contact: Mona Frolova, PhD \| +74993241880 \| drfrolova@yandex.ru Principal Investigator: Mona Frolova, PhD Recruiting