Neoadjuvant Carboplatin in Triple Negative Breast Cancer

Study Overview
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Brief Summary
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Breast cancer is the most frequent neoplasm in women in Brazil and in the world and up to 15% of all cases diagnosed correspond to the triple negative subtype. Triple negative breast cancer affects young women with germline mutations in BRCA 1/2 genes. Giving the lack of target therapies to date, there is no consensus regarding the most effective treatment for this subgroup of tumors. Although evidence shows that triple negative breast cancer is highly sensitive to chemotherapy when compared to other breast tumors, there is no evidence to support the hypothesis that patients with triple negative breast cancer and mutation in BRCA1 / 2 genes have higher chemosensitivity to neoadjuvant therapy. The investigator proposes a prospective, randomized, open-label, phase II study, evaluating the rate of complete pathologic response, disease-free survival, overall survival and prognostic evaluation of BRCA1 / 2 mutation status in women with triple negative breast cancer submitted to sequential neoadjuvant chemotherapy based on anthracycline and taxane, with or without carboplatin.

Official Title
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Neoadjuvant Carboplatin in Triple Negative Breast Cancer - A Prospective Phase II Study (NACATRINE Trial).

Conditions
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BRCA1 Hereditary Breast and Ovarian Cancer Syndrome

Intervention / Treatment
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* Drug: Doxorubicin
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Triple Negative Breast Cancer; Stage II or III; Performance Status ECOG <2 or Karnofsky >50%; Hematologic (minimal values): Absolute neutrophil count > 1,500/mm3 Hemoglobin > 10.0 g/dl Platelet count > 100,000/mm3 Exclusion Criteria: Stage I or IV; other malignancies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A- BRCA Mutation<br>Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by: Paclitaxel 80 mg/m2 once a week, for 12 weeks, concomitant to Carboplatin AUC 1,5 once a week, for 12 weeks. | Drug: Doxorubicin<br>* Doxorrubicin 60 mg/m2 4 cycles each 21 days<br>Drug: Carboplatin<br>* Carboplatin AUC 1,5 once a week, for 12 weeks<br>Drug: Paclitaxel<br>* 80mg/m2 weekly for 12 weeks<br>Drug: Cyclophosphamide<br>* 600mg/m2 4 cycles each 21 days<br>|
| Active Comparator: B- BRCA Mutation<br>Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by: Paclitaxel 80 mg/m2 once a week, for 12 weeks. | Drug: Doxorubicin<br>* Doxorrubicin 60 mg/m2 4 cycles each 21 days<br>Drug: Paclitaxel<br>* 80mg/m2 weekly for 12 weeks<br>Drug: Cyclophosphamide<br>* 600mg/m2 4 cycles each 21 days<br>|
| Experimental: C- BRCA wild-type<br>Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by: Paclitaxel 80 mg/m2 once a week, for 12 weeks, concomitant to Carboplatin AUC 1,5 once a week, for 12 weeks. | Drug: Doxorubicin<br>* Doxorrubicin 60 mg/m2 4 cycles each 21 days<br>Drug: Carboplatin<br>* Carboplatin AUC 1,5 once a week, for 12 weeks<br>Drug: Paclitaxel<br>* 80mg/m2 weekly for 12 weeks<br>Drug: Cyclophosphamide<br>* 600mg/m2 4 cycles each 21 days<br>|
| Active Comparator: D- BRCA wild-type<br>Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by: Paclitaxel 80 mg/m2 once a week, for 12 weeks. | Drug: Doxorubicin<br>* Doxorrubicin 60 mg/m2 4 cycles each 21 days<br>Drug: Paclitaxel<br>* 80mg/m2 weekly for 12 weeks<br>Drug: Cyclophosphamide<br>* 600mg/m2 4 cycles each 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR), defined as absence of invasive cancer in the breast and axillary lymph nodes. |  | within the first 21 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival (DFS) |  | within the first 60 month after surgery | 
| Overall survival (OS) |  | within the first 60 month after surgery |