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

Breast Cancer Clinical Trial

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"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00432172
• Other study ID #: GEICAM/2006-03
• Status: Completed
• Phase: Phase 2
• Start date: April 24, 2007
• Est. completion date: September 1, 2010

Study information

• Verified date: March 2023
• Source: Spanish Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: September 1, 2010
• Est. primary completion date: September 1, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Epirubicin

• Cyclophosphamide

• Docetaxel

• Exemestane

• Goserelin

• Carboplatin

Locations

Country	Name	City	State
Spain	Centro Oncológico Regional de Galicia	A Coruña
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital General de Alicante	Alicante
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Onkologikoa	Donostia	Gipuzkoa
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital de la Princesa	Madrid
Spain	Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona
Spain	Hospital Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Clínico Universitario de Valencia	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	Pfizer

Country where clinical trial is conducted

Spain, 

References & Publications (8)

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 cance — View 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 b — View 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, — View 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-embedde — View 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 Neutro — View 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, Vi — View 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, Marti — View 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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological Response for Basal Group 2	This primary outcome only applies for the basal group 2 as per protocol. The pathological response in luminal group 1 was not pre-specified even as a Secondary Outcome. Pathological response was assessed after surgery, according to the Miller & Payne criteria, which stratifies the responses based on the proportion of remaining tumor and post-chemotherapy changes, evaluating separately the response in breast and axilla. Grades 1-4 are categorised as a partial pathological response (pPR) and grade 5 was a complete pathological response (cPR).	Up to 24 weeks
Secondary	Clinical Response Rate	Clinical Response Rate was measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria for target lesions before surgery: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to week 24
Secondary	Breast Conservative Surgery Rate	All patients will undergo surgery within the expected period from the end of treatment with neoadjuvant therapy. The chosen surgical option will be collected in the Case Report Form (CRF) before starting the neoadjuvant treatment, depending on the characteristics Clinics of the patient at that time (conservative surgery or mastectomy). This information will be compared with definitive surgery, to analyze whether neoadjuvant treatment has contributed to increase the rate of conservative surgery.	Up to 24 weeks
Secondary	Axillary Node Status at the Time of Surgery	All the patients underwent lymphadenectomy in the foreseen term from the end of the treatment with neoadjuvant therapy, except for patients who underwent the technique of Sentinel lymph node with negative result before the start of the study treatment.; Clinical lymph node involvement were collected in the CRF. Behind the lymphadenectomy, the rate of patients with affected lymph nodes, regardless of the type of response in the breast. To help find out if the cancer has spread outside the breast, one or more of the lymph nodes in the axilla (axillary lymph nodes) are removed for examination under a microscope. This is an important part of the determination of the stage. When the lymph nodes have cancer cells, there is a greater chance that the cancer cells have spread to other parts of the body. Decisions about treatment will depend on whether there is cancer in the lymph nodes.	Up to 24 weeks

External Links

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