Neoadjuvant Chemotherapy With Myocet/Taxotere/Herceptin for HER2 Positive Breast Cancer Patients

NCT ID: NCT00129896

Last Updated: 2023-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2010-02-28

Brief Summary

This is an open-label study to assess the efficacy and tolerability of the combination Myocet®/Taxotere®/Herceptin® as primary treatment for HER2 positive breast cancer patients. HER2 status will be confirmed centrally by fluorescence in situ hybridization (FISH).

Phase I: Initial doses will be:

Myocet: 50-60 mg/m² day 1 every 3 weeks; Taxotere 60-75 mg/m² day 1 every 3 weeks; and Herceptin (4) 2 mg/kg weekly.

Sample size will depend on the number of patients recruited during dose escalation. Three patients must be recruited in each dose level. If one out of three experiences a dose-limiting toxicity (DLT), 3 more patients must be recruited in the same dose level. Considering that there are 4 dose levels to be tested, the estimated number of patients is 9 to 24. Patients receiving the recommended dose (RD) will be incorporated into phase II of the study.

Detailed Description

Phase II: The average pathological complete response rate reported in other trials is around 11%. The investigators expect to achieve an increase of 14% on this rate; that is, they expect a pathological response rate of 25%. With a= 0.05 and β=0.2, 18 patients are initially needed. If at least 3 pathological complete responses are achieved, recruitment will continue to up to 53 patients. At least 10 pathological complete responses are needed to probe the hypothesis. Considering a 10% post-randomization drop-out rate, a total of 59 patients must be recruited for the trial.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Myocet+Taxotere+Herceptin

Myocet 50 mg/m2; Taxotere 60 mg/m2; Herceptín 4 mg/Kg (first dose) and in the following cycles 2 mg/Kg

Group Type: EXPERIMENTAL

Myocet

Intervention Type: DRUG

Myocet®: 60-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles

Taxotere

Intervention Type: DRUG

Taxotere® 70-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles

Herceptin

Intervention Type: DRUG

Herceptin® (4) 2 mg/kg (vía IV) Semanal for 6 cycles

Interventions

Myocet

Myocet®: 60-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles

Intervention Type: DRUG

Taxotere

Taxotere® 70-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles

Intervention Type: DRUG

Herceptin

Herceptin® (4) 2 mg/kg (vía IV) Semanal for 6 cycles

Intervention Type: DRUG

Other Intervention Names

Lyposomal Doxorubicin; Docetaxel; Trastuzumab

Eligibility Criteria

Inclusion Criteria

• Written informed consent.
• Breast cancer stages II and IIIA with histological diagnoses by true-cut.
• Breast cancer tumours overexpressing HER2neu, centrally confirmed by FISH.
• No evidence of metastasis: bilateral mammography, thorax x-ray, computed tomography (CT)-scan or abdominal echography and bone scintigraphy.
• Estrogen and progesterone hormone receptor status, determined before study registration.
• Age >= 18 years old.
• Performance status (Karnofsky index) >= 80.
• Adequate cardiac function by LVEF in the previous 14 days.
• Hematology: neutrophils >= 2.0 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >= 10 g/dl.
• Adequate hepatic function: total bilirubin <= 1x upper normal limit (UNL); SGOT and SGPT <= 2.5xUNL; alkaline phosphatase <= 2.5xUNL.
• Adequate renal function: creatinine <= 1xUNL; creatinine clearance >= 60 ml/min.
• Patients able to comply with study treatment and follow-up.
• Negative pregnancy test in the previous 14 days.
• Adequate contraceptive method during the study and up to 3 months after definitive surgery.

Exclusion Criteria

• HER2neu negative tumours.
• Prior systemic therapy for breast cancer.
• 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 [NCI CTC]).
• 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, anthracyclines, docetaxel, trastuzumab or egg derivates.
• Concomitant treatment with other therapy for cancer.
• Males.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cephalon

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

Spanish Breast Cancer Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Hospital Univesitario Miguel Servet

Locations

Hospital Universitario Virgen de los Lirios

Alcoy, Alicante, Spain

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain

Althaia-Xarxa Assistencial de Manresa

Manresa, Barcelona, Spain

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, Spain

Consorci Sanitari de Terrassa

Terrassa, Barcelona, Spain

Onkologikoa

Donostia / San Sebastian, Guipúzcoa, Spain

Hospital de la Ribera

Alzira, Valencia, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Hospital Infanta Cristina

Badajoz, , Spain

Hospital Clinic i Provincial

Barcelona, , Spain

Complejo Hospitalario de Jaén

Jaén, , Spain

Hospital Universitario Lucus Augusti

Lugo, , Spain

Hospital Clínico Universitario Virgen de la Victoria

Málaga, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

Spain

References

Anton A, Ruiz A, Plazaola A, Calvo L, Segui MA, Santaballa A, Munoz M, Sanchez P, Miguel A, Carrasco E, Lao J, Camps J, Alfaro J, Antolin S, Camara MC. Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003-03 study. Ann Oncol. 2011 Jan;22(1):74-79. doi: 10.1093/annonc/mdq317. Epub 2010 Jul 5.

Reference Type: RESULT

PMID: 20603435 (View on PubMed)

Anton A, Ruiz A, Segui MA, Calvo L, Munoz M, Lao J, Sancho F, Fernandez L. Phase I clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neo-adjuvant treatment in stages II and IIIA, HER2-overexpressing breast cancer patients. GEICAM 2003-03 study. Ann Oncol. 2009 Mar;20(3):454-9. doi: 10.1093/annonc/mdn663. Epub 2008 Dec 11.

Reference Type: RESULT

PMID: 19074216 (View on PubMed)

Related Links

http://www.geicam.org

Click here for more information about this study: GEICAM 2003-03

Other Identifiers

GEICAM 2003-03

Identifier Type: -

Identifier Source: org_study_id