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

Sponsor

Spanish Breast Cancer Research Group (Other)

Overall Status

Completed

CT.gov ID

NCT00129896

Collaborator

Cephalon (Industry), Sanofi (Industry), Hoffmann-La Roche (Industry), Amgen (Industry)

Enrollment

Locations

Arm

Actual Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Myocet Drug: Taxotere Drug: Herceptin	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

73 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 1, 2004

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Myocet Myocet®: 60-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles Other Names: Lyposomal Doxorubicin Drug: Taxotere Taxotere® 70-75 mg/m² ASC (vía IV) día 1 / c3s for 6 cycles Other Names: Docetaxel Drug: Herceptin Herceptin® (4) 2 mg/kg (vía IV) Semanal for 6 cycles Other Names: Trastuzumab

Arm

Intervention/Treatment

Experimental: 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

Drug: Myocet

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

Other Names:

Lyposomal Doxorubicin

Drug: Taxotere

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

Other Names:

Docetaxel

Drug: Herceptin

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

Other Names:

Trastuzumab

Outcome Measures

Primary Outcome Measures

Tolerability (Phase I): Recommended Doses of the combination treatment [up to 24 months since last patient included in the Phase I]
Recommended Doses of the combination treatment
Efficacy (Phase II): Percentage (%) pathological Complete Response achieved according to Miller and Payne Criteria [up to 24 months since last patient included in the Phase II]
% pathological Complete Response achieved according to Miller and Payne Criteria

Secondary Outcome Measures

Clinical response rates [up to 6 months since last patient treatment]
Clinical responses evaluated by radiological imaging
Surgery type (conservative surgery versus mastectomy) [up to 7 months since last patient treatment]
% conservative or mastectomy surgery
Potential cardiac toxicity [up to 12 months since last patient included]
Left ventricular ejection fraction [LVEF] by multiple-gated acquisition [MUGA])
Safety: Adverse Events evaluated according to NCI CTC v2.0 [24 months since last patient included]
Adverse Events evaluated according to NCI CTC v2.0
Post-surgery node status [up to 7 months since last patient treatment]
according to Miller and Payne Criteria
Molecular changes in blood and tissue exams [24 months]
Different biomarkers evaluated

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Virgen de los Lirios	Alcoy	Alicante	Spain	03804
2	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
3	Althaia-Xarxa Assistencial de Manresa	Manresa	Barcelona	Spain	08243
4	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona	Spain	08208
5	Consorci Sanitari de Terrassa	Terrassa	Barcelona	Spain	08227
6	Onkologikoa	Donostia-San Sebastian	Guipúzcoa	Spain	20012
7	Hospital de la Ribera	Alzira	Valencia	Spain	46600
8	Complejo Hospitalario Universitario A Coruña	A Coruña		Spain	15006
9	Hospital Infanta Cristina	Badajoz		Spain	06080
10	Hospital Clinic i Provincial	Barcelona		Spain	08036
11	Complejo Hospitalario de Jaén	Jaén		Spain	23007
12	Hospital Universitario Lucus Augusti	Lugo		Spain	27004
13	Hospital Clínico Universitario Virgen de la Victoria	Málaga		Spain	29010
14	Instituto Valenciano de Oncología	Valencia		Spain	46009
15	Hospital Universitario La Fe	Valencia		Spain	46026
16	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009