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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Russian Academy of Medical Sciences
Sponsor:
Information provided by (Responsible Party):
Mona Frolova, Russian Academy of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01672671
First received: August 16, 2012
Last updated: May 21, 2013
Last verified: May 2013
  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 Intervention Phase
Early Triple Negative Breast Cancer
Drug: Doxorubicin, Paclitaxel, Cisplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Identification of BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy

Resource links provided by NLM:


Further study details as provided by Russian Academy of Medical Sciences:

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.


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 ]

Other Outcome Measures:
  • Number of patients with 3/4 Grade CTC adverse events to assess toxicity and tolerability of the chemotherapy regimen [ Time Frame: after 8 weeks of neadjuvant chemotherapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: August 2011
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neoadjuvant platinum-based chemotherapy
Doxorubicin, Paclitaxel, Cisplatin
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01672671

Contacts
Contact: Mona Frolova, PhD +74993241880 drfrolova@yandex.ru
Contact: Ekaterina Ignatova +74993241900 md.ignatova@gmail.com

Locations
Russian Federation
Russian Cancer Research Center named after N.N.Blokhin RAMS Recruiting
Moscow, Russian Federation, 115478
Contact: Mona Frolova, PhD    +74993241880    drfrolova@yandex.ru   
Contact: Ekaterina Ignatova    +74993241900    md.ignatova@gmail.com   
Principal Investigator: Mona Frolova, PhD         
Sponsors and Collaborators
Russian Academy of Medical Sciences
  More Information

Additional Information:
No publications provided

Responsible Party: Mona Frolova, Research Associate of Department of Clinical Pharmacology and Chemotherapy, Russian Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT01672671     History of Changes
Other Study ID Numbers: TNNP 001, TNNP 001
Study First Received: August 16, 2012
Last Updated: May 21, 2013
Health Authority: Russia: Ethics Committee

Additional relevant MeSH terms:
Triple Negative Breast Neoplasms
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cisplatin
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014