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

Breast Cancer Clinical Trial

Official title:

Open-label Phase I-II Clinical Trial to Evaluate Treatment With Myocet/Taxotere/Herceptin as Primary Chemotherapy Treatment for HER2neu Positive Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129896
• Other study ID #: GEICAM 2003-03
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2004
• Est. completion date: February 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: February 2010
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Myocet
Myocet®: 60-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles
• Taxotere
Taxotere® 70-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles
• Herceptin
Herceptin® (4) 2 mg/kg (vía IV) Semanal for 6 cycles

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Universitario Virgen de los Lirios	Alcoy	Alicante
Spain	Hospital de la Ribera	Alzira	Valencia
Spain	Hospital Infanta Cristina	Badajoz
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Onkologikoa	Donostia-San Sebastian	Guipúzcoa
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	Althaia-Xarxa Assistencial de Manresa	Manresa	Barcelona
Spain	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona
Spain	Hospital Universitario La Fe	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (5)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	Amgen, Cephalon, Hoffmann-La Roche, Sanofi

Country where clinical trial is conducted

Spain, 

References & Publications (2)

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 tr — View Citation

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-overexpressin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerability (Phase I): Recommended Doses of the combination treatment	Recommended Doses of the combination treatment	up to 24 months since last patient included in the Phase I
Primary	Efficacy (Phase II): Percentage (%) pathological Complete Response achieved according to Miller and Payne Criteria	% pathological Complete Response achieved according to Miller and Payne Criteria	up to 24 months since last patient included in the Phase II
Secondary	Clinical response rates	Clinical responses evaluated by radiological imaging	up to 6 months since last patient treatment
Secondary	Surgery type (conservative surgery versus mastectomy)	% conservative or mastectomy surgery	up to 7 months since last patient treatment
Secondary	Potential cardiac toxicity	Left ventricular ejection fraction [LVEF] by multiple-gated acquisition [MUGA])	up to 12 months since last patient included
Secondary	Safety: Adverse Events evaluated according to NCI CTC v2.0	Adverse Events evaluated according to NCI CTC v2.0	24 months since last patient included
Secondary	Post-surgery node status	according to Miller and Payne Criteria	up to 7 months since last patient treatment
Secondary	Molecular changes in blood and tissue exams	Different biomarkers evaluated	24 months

External Links

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