Neoadjuvant Carboplatin in Triple Negative Breast Cancer

NCT ID: NCT02978495

Last Updated: 2022-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-17

Study Completion Date

2021-10-22

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.

Detailed Description

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Conditions

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BRCA1 Hereditary Breast and Ovarian Cancer Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A- BRCA Mutation

1. Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by:
2. Paclitaxel 80 mg/m2 once a week, for 12 weeks, concomitant to Carboplatin AUC 1,5 once a week, for 12 weeks.

Group Type EXPERIMENTAL

Doxorubicin

Intervention Type DRUG

Doxorrubicin 60 mg/m2 4 cycles each 21 days

Carboplatin

Intervention Type DRUG

Carboplatin AUC 1,5 once a week, for 12 weeks

Paclitaxel

Intervention Type DRUG

80mg/m2 weekly for 12 weeks

Cyclophosphamide

Intervention Type DRUG

600mg/m2 4 cycles each 21 days

B- BRCA Mutation

1. Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by:
2. Paclitaxel 80 mg/m2 once a week, for 12 weeks.

Group Type ACTIVE_COMPARATOR

Doxorubicin

Intervention Type DRUG

Doxorrubicin 60 mg/m2 4 cycles each 21 days

Paclitaxel

Intervention Type DRUG

80mg/m2 weekly for 12 weeks

Cyclophosphamide

Intervention Type DRUG

600mg/m2 4 cycles each 21 days

C- BRCA wild-type

1. Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by:
2. Paclitaxel 80 mg/m2 once a week, for 12 weeks, concomitant to Carboplatin AUC 1,5 once a week, for 12 weeks.

Group Type EXPERIMENTAL

Doxorubicin

Intervention Type DRUG

Doxorrubicin 60 mg/m2 4 cycles each 21 days

Carboplatin

Intervention Type DRUG

Carboplatin AUC 1,5 once a week, for 12 weeks

Paclitaxel

Intervention Type DRUG

80mg/m2 weekly for 12 weeks

Cyclophosphamide

Intervention Type DRUG

600mg/m2 4 cycles each 21 days

D- BRCA wild-type

1. Doxorrubicin 60 mg/m2 concomitantly with Cyclophosphamide 600mg/m2, every 3 weeks, for 4 cycles followed by:
2. Paclitaxel 80 mg/m2 once a week, for 12 weeks.

Group Type ACTIVE_COMPARATOR

Doxorubicin

Intervention Type DRUG

Doxorrubicin 60 mg/m2 4 cycles each 21 days

Paclitaxel

Intervention Type DRUG

80mg/m2 weekly for 12 weeks

Cyclophosphamide

Intervention Type DRUG

600mg/m2 4 cycles each 21 days

Interventions

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Doxorubicin

Doxorrubicin 60 mg/m2 4 cycles each 21 days

Intervention Type DRUG

Carboplatin

Carboplatin AUC 1,5 once a week, for 12 weeks

Intervention Type DRUG

Paclitaxel

80mg/m2 weekly for 12 weeks

Intervention Type DRUG

Cyclophosphamide

600mg/m2 4 cycles each 21 days

Intervention Type DRUG

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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Barretos Cancer Hospital

OTHER

Sponsor Role lead

Responsible Party

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Cristiano de Padua

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Barretos Cancer Hospital

Barretos, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kummel S, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014 Jun;15(7):747-56. doi: 10.1016/S1470-2045(14)70160-3. Epub 2014 Apr 30.

Reference Type RESULT
PMID: 24794243 (View on PubMed)

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Reference Type RESULT
PMID: 24136883 (View on PubMed)

Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, Dent R, Lubinski J, Narod S. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010 Jan 20;28(3):375-9. doi: 10.1200/JCO.2008.20.7019. Epub 2009 Dec 14.

Reference Type RESULT
PMID: 20008645 (View on PubMed)

Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. doi: 10.1200/JCO.2014.57.0572. Epub 2014 Aug 4.

Reference Type RESULT
PMID: 25092775 (View on PubMed)

Valsecchi ME, Kimmey G, Bir A, Silbermins D. Role of Carboplatin in the Treatment of Triple Negative Early- Stage Breast Cancer. Rev Recent Clin Trials. 2015;10(2):101-10. doi: 10.2174/1574887110666150624101343.

Reference Type RESULT
PMID: 26104428 (View on PubMed)

Arun B, Bayraktar S, Liu DD, Gutierrez Barrera AM, Atchley D, Pusztai L, Litton JK, Valero V, Meric-Bernstam F, Hortobagyi GN, Albarracin C. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J Clin Oncol. 2011 Oct 1;29(28):3739-46. doi: 10.1200/JCO.2011.35.2682. Epub 2011 Sep 6.

Reference Type RESULT
PMID: 21900106 (View on PubMed)

Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, Lanchbury JS, Stemke-Hale K, Hennessy BT, Arun BK, Hortobagyi GN, Do KA, Mills GB, Meric-Bernstam F. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res. 2011 Mar 1;17(5):1082-9. doi: 10.1158/1078-0432.CCR-10-2560. Epub 2011 Jan 13.

Reference Type RESULT
PMID: 21233401 (View on PubMed)

Paluch-Shimon S, Friedman E, Berger R, Papa M, Dadiani M, Friedman N, Shabtai M, Zippel D, Gutman M, Golan T, Yosepovich A, Catane R, Modiano T, Kaufman B. Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers. Breast Cancer Res Treat. 2016 May;157(1):157-65. doi: 10.1007/s10549-016-3800-5. Epub 2016 Apr 25.

Reference Type RESULT
PMID: 27113739 (View on PubMed)

Muendlein A, Rohde BH, Gasser K, Haid A, Rauch S, Kinz E, Drexel H, Hofmann W, Schindler V, Kapoor R, Decker T, Lang AH. Evaluation of BRCA1/2 mutational status among German and Austrian women with triple-negative breast cancer. J Cancer Res Clin Oncol. 2015 Nov;141(11):2005-12. doi: 10.1007/s00432-015-1986-2. Epub 2015 May 15.

Reference Type RESULT
PMID: 25971625 (View on PubMed)

Other Identifiers

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BarretosCH - 20162

Identifier Type: -

Identifier Source: org_study_id