Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients

NCT ID: NCT00432172

Last Updated: 2023-04-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

189 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-24

Study Completion Date

2010-09-01

Brief Summary

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This is an open-label study that includes two substudies of random distribution. First,a sample of the primary tumor will be obtained and will be analyzed by an immunohistochemical technique to determine several markers.Depending on the expression of these markers, the patients will be characterize as group 1 (Luminal A phenotype) or group 2 (Basal phenotype) and a random assignment will be performed to standard or experimental treatment.

Detailed Description

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Group 1 (Luminal A):

* Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

EC x 4 -\> D x 4

* Selective treatment: Postmenopausal patients: exemestane x 6 months; Premenopausal patients: goserelin x 6 months + exemestane x 6 months

Group 2 (Basal):

* Standard treatment: EC x 4 -\> D x 4
* Selective treatment: E 90 mg/ m2 iv in combination with C 600 mg/ m2 iv every 21 days for 4 cycles, followed by D (75 mg/m2) and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.

EC x 4 -\> DCb x 4

Conditions

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Breast Cancer

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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Group 1 (Luminal A) Standard treatment

Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

Group Type ACTIVE_COMPARATOR

Epirubicin

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Group 1 (Luminal A) Selective treatment

Selective treatment:

Postmenopausal patients: exemestane x 6 months Premenopausal patients: goserelin x 6 months + exemestane x 6 months

Group Type EXPERIMENTAL

Exemestane

Intervention Type DRUG

Goserelin

Intervention Type DRUG

Group 2 (Basal) Standard treatment

Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

Group Type ACTIVE_COMPARATOR

Epirubicin

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Group 2 (Basal) Selective treatment

Selective treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.

Group Type EXPERIMENTAL

Epirubicin

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Interventions

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Epirubicin

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Exemestane

Intervention Type DRUG

Goserelin

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Other Intervention Names

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Ellence Cytoxan Taxotere aromasil Zoladex Paraplatin

Eligibility Criteria

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Inclusion Criteria

* Written informed consent.
* Breast cancer with histological diagnosis.
* Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours defined as immunohistochemistry (IHQ) 0,1+.
* No evidence of suspicion of metastatic disease.
* Age \>= 18 years old.
* Performance status (Karnofsky index) \>= 80 (ECOG 0,1).
* Adequate cardiac function by ECG in the previous 12 weeks.
* Hematology: neutrophils \>= 1,5 x10\^9/l; platelets \>= 100 x10\^9/l; hemoglobin \>= 10 g/dl.
* Adequate hepatic function: total bilirubin \<= 1x Upper Normal Limit (UNL); Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) \<= 2.5 x UNL; alkaline phosphatase \<= 2.5 x UNL.
* Adequate renal function: creatinine \<= 1 x UNL; creatinine clearance \>= 60 ml/min.
* Patients able to comply with study treatment and follow-up.
* Negative pregnancy test in the previous 14 days.

Exclusion Criteria

* HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization \[FISH\]).
* Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
* Prior treatment with anthracyclines or taxanes (paclitaxel, docetaxel) for any previous malignancy.
* Prior radiotherapy for breast cancer.
* Bilateral invasive breast cancer.
* Pregnant or lactating women.
* Previous grade \>= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria \[NCICTC\]).
* Other serious comorbidities: congestive heart failure or unstable angina; prior history of myocardial infarction in previous year; uncontrolled hypertension (HT); high risk arrhythmias; history of significant neurological or psychiatric disorders; uncontrolled active infection; active peptic ulcer; unstable diabetes mellitus; dyspnea at rest; or chronic therapy with oxygen.
* Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.
* Chronic treatment with corticosteroids.
* Contraindications for administration of corticosteroids.
* Concomitant treatment with other therapy for cancer.
* Males.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Spanish Breast Cancer Research Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Hospital Miguel Servet

Locations

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Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, Spain

Site Status

Hospital Mutua de Terrassa

Terrassa, Barcelona, Spain

Site Status

Onkologikoa

Donostia / San Sebastian, Gipuzkoa, Spain

Site Status

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Site Status

Centro Oncológico Regional de Galicia

A Coruña, , Spain

Site Status

Hospital General de Alicante

Alicante, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofía

Córdoba, , Spain

Site Status

Complejo Hospitalario de Jaén

Jaén, , Spain

Site Status

Hospital de la Princesa

Madrid, , Spain

Site Status

Hospital Clínico Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Countries

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Spain

References

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Alba E, Chacon JI, Lluch A, Anton A, Estevez L, Cirauqui B, Carrasco E, Calvo L, Segui MA, Ribelles N, Alvarez R, Sanchez-Munoz A, Sanchez R, Garcia-Asenjo JA, Rodriguez-Martin C, Escudero MJ, Albanell J. A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study. Breast Cancer Res Treat. 2012 Nov;136(2):487-93. doi: 10.1007/s10549-012-2100-y. Epub 2012 Oct 9.

Reference Type RESULT
PMID: 23053638 (View on PubMed)

Alba E, Calvo L, Albanell J, De la Haba JR, Arcusa Lanza A, Chacon JI, Sanchez-Rovira P, Plazaola A, Lopez Garcia-Asenjo JA, Bermejo B, Carrasco E, Lluch A; GEICAM. Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. Ann Oncol. 2012 Dec;23(12):3069-3074. doi: 10.1093/annonc/mds132. Epub 2012 Jun 6.

Reference Type RESULT
PMID: 22674146 (View on PubMed)

Prat A, Lluch A, Albanell J, Barry WT, Fan C, Chacon JI, Parker JS, Calvo L, Plazaola A, Arcusa A, Segui-Palmer MA, Burgues O, Ribelles N, Rodriguez-Lescure A, Guerrero A, Ruiz-Borrego M, Munarriz B, Lopez JA, Adamo B, Cheang MC, Li Y, Hu Z, Gulley ML, Vidal MJ, Pitcher BN, Liu MC, Citron ML, Ellis MJ, Mardis E, Vickery T, Hudis CA, Winer EP, Carey LA, Caballero R, Carrasco E, Martin M, Perou CM, Alba E. Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer. 2014 Oct 14;111(8):1532-41. doi: 10.1038/bjc.2014.444. Epub 2014 Aug 7.

Reference Type RESULT
PMID: 25101563 (View on PubMed)

Prat A, Lluch A, Turnbull AK, Dunbier AK, Calvo L, Albanell J, de la Haba-Rodriguez J, Arcusa A, Chacon JI, Sanchez-Rovira P, Plazaola A, Munoz M, Pare L, Parker JS, Ribelles N, Jimenez B, Bin Aiderus AA, Caballero R, Adamo B, Dowsett M, Carrasco E, Martin M, Dixon JM, Perou CM, Alba E. A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse. Clin Cancer Res. 2017 Jun 15;23(12):3035-3044. doi: 10.1158/1078-0432.CCR-16-2092. Epub 2016 Nov 30.

Reference Type RESULT
PMID: 27903675 (View on PubMed)

Alba E, Lluch A, Ribelles N, Anton-Torres A, Sanchez-Rovira P, Albanell J, Calvo L, Garcia-Asenjo JA, Palacios J, Chacon JI, Ruiz A, De la Haba-Rodriguez J, Segui-Palmer MA, Cirauqui B, Margeli M, Plazaola A, Barnadas A, Casas M, Caballero R, Carrasco E, Rojo F. High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer. Oncologist. 2016 Feb;21(2):150-5. doi: 10.1634/theoncologist.2015-0312. Epub 2016 Jan 19.

Reference Type RESULT
PMID: 26786263 (View on PubMed)

Chin SF, Santonja A, Grzelak M, Ahn S, Sammut SJ, Clifford H, Rueda OM, Pugh M, Goldgraben MA, Bardwell HA, Cho EY, Provenzano E, Rojo F, Alba E, Caldas C. Shallow whole genome sequencing for robust copy number profiling of formalin-fixed paraffin-embedded breast cancers. Exp Mol Pathol. 2018 Jun;104(3):161-169. doi: 10.1016/j.yexmp.2018.03.006. Epub 2018 Mar 31.

Reference Type RESULT
PMID: 29608913 (View on PubMed)

Santonja A, Sanchez-Munoz A, Lluch A, Chica-Parrado MR, Albanell J, Chacon JI, Antolin S, Jerez JM, de la Haba J, de Luque V, Fernandez-De Sousa CE, Vicioso L, Plata Y, Ramirez-Tortosa CL, Alvarez M, Llacer C, Zarcos-Pedrinaci I, Carrasco E, Caballero R, Martin M, Alba E. Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy. Oncotarget. 2018 May 29;9(41):26406-26416. doi: 10.18632/oncotarget.25413. eCollection 2018 May 29.

Reference Type RESULT
PMID: 29899867 (View on PubMed)

Ocana A, Chacon JI, Calvo L, Anton A, Mansutti M, Albanell J, Martinez MT, Lahuerta A, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chan A, Morales S, Herranz J, Tusquets I, Chiesa M, Caballero R, Valagussa P, Bianchini G, Alba E, Gianni L. Derived Neutrophil-to-Lymphocyte Ratio Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer. Front Oncol. 2022 Feb 11;11:827625. doi: 10.3389/fonc.2021.827625. eCollection 2021.

Reference Type RESULT
PMID: 35223459 (View on PubMed)

Related Links

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http://www.geicam.org

Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Other Identifiers

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GEICAM/2006-03

Identifier Type: -

Identifier Source: org_study_id

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