Clinical trial NCT00129896: Neoadjuvant Chemotherapy With Myocet/Taxotere/Herceptin for HER2 Positive Breast Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Her2neu positive breast cancer.
Neoadjuvant treatment.
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Cephalon
name: Sanofi
name: Hoffmann-La Roche
name: Amgen
First posted: 2005-08-12
Enrollment: 73
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Tolerability (Phase I): Recommended Doses of the combination treatment
timeFrame: up to 24 months since last patient included in the Phase I
measure: Efficacy (Phase II): Percentage (%) pathological Complete Response achieved according to Miller and Payne Criteria
timeFrame: up to 24 months since last patient included in the Phase II
Secondary outcomes:
measure: Clinical response rates
timeFrame: up to 6 months since last patient treatment
measure: Surgery type (conservative surgery versus mastectomy)
timeFrame: up to 7 months since last patient treatment
measure: Potential cardiac toxicity
timeFrame: up to 12 months since last patient included
measure: Safety: Adverse Events evaluated according to NCI CTC v2.0
timeFrame: 24 months since last patient included
measure: Post-surgery node status
timeFrame: up to 7 months since last patient treatment
measure: Molecular changes in blood and tissue exams
timeFrame: 24 months
Other outcomes:
Locations:
city: Alcoy
country: Spain
facility: Hospital Universitario Virgen de los Lirios
state: Alicante
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Manresa
country: Spain
facility: Althaia-Xarxa Assistencial de Manresa
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Donostia-San Sebastian
country: Spain
facility: Onkologikoa
state: Guipúzcoa
city: Alzira
country: Spain
facility: Hospital de la Ribera
state: Valencia
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Málaga
country: Spain
facility: Hospital Clínico Universitario Virgen de la Victoria
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital Univesitario Miguel Servet
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
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-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.