Clinical trial NCT00432172: Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients
Official title: "A Randomized Multicenter Phase II Trial to Evaluate the Effectiveness of Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Her2neu negative breast cancer.
Neoadjuvant treatment.
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2007-02-07
Enrollment: 189
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Pathological Response for Basal Group 2
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Clinical Response Rate
timeFrame: Up to week 24
measure: Breast Conservative Surgery Rate
timeFrame: Up to 24 weeks
measure: Axillary Node Status at the Time of Surgery
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Donostia
country: Spain
facility: Onkologikoa
state: Gipuzkoa
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: A Coruña
country: Spain
facility: Centro Oncológico Regional de Galicia
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: Madrid
country: Spain
facility: Hospital de la Princesa
city: Málaga
country: Spain
facility: Hospital Clínico Universitario Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Hospital Miguel Servet
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.