Trastuzumab Versus Lapatinib as Neoadjuvant Treatment for Her2+ Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT00841828
First received: February 9, 2009
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

Phase II randomized multicenter Trial to compare Epirubicine and Cyclophosphamide plus Docetaxel and Trastuzumab with Epirubicine and Cyclophosphamide plus Docetaxel and Lapatinib for patients with positive HER2 neu and resectable breast cancer or locally advanced breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Epirubicin, Cyclophosphamide, Taxotere, Herceptín, Lapatinib
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomised, Multicentre Compare Epirubicine and Cyclophosphamide Treatment Plus Docetaxel and Trastuzumab Versus Epirubicine and Cyclophosphamide Treatment Plus Docetaxel and Lapatinib in Women With Primary Resectable Breast Cancer or Locally Advanced Breast Cancer Positive Her 2.

Resource links provided by NLM:


Further study details as provided by Spanish Breast Cancer Research Group:

Primary Outcome Measures:
  • Complete pathological response Rate [ Time Frame: Within 3-4 weeks after last docetaxel dose, surgery will be performed to evaluate pathological response ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity assessment [ Time Frame: After each treatment cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 102
Study Start Date: February 2009
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

EC -> T + Lapatinib

Drugs plus Biological

Drug: Epirubicin, Cyclophosphamide, Taxotere, Herceptín, Lapatinib

- EC (each 21 days for 4 cycles) -> T + lapatinib (each 21 days for 4 cycles) vs

EC (each 21 days for 4 cycles) -> T + herceptin (each 21 days for 4 cycles)

Active Comparator: 2

EC -> T + Trastuzumab

Drug plus Biological

Drug: Epirubicin, Cyclophosphamide, Taxotere, Herceptín, Lapatinib

- EC (each 21 days for 4 cycles) -> T + lapatinib (each 21 days for 4 cycles) vs

EC (each 21 days for 4 cycles) -> T + herceptin (each 21 days for 4 cycles)


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signature of the written informed consent.
  2. Histological documentation of breast cancer.
  3. Stage I (T1, N0M0), IIA (T2N0M0); IIB (T2N1M0, T3N0M0), IIIA (TXN2M0) and IIIB (T3N1M0, T4NXM0) primary resectable breast cancer or locally advanced breast cancer.
  4. HER2-positive breast cancer, defined as IHC 3+ or positive FISH. When IHC 2+ HER2 status must be assessed by FISH.
  5. The patient granted her consent for taking a biopsy before treatment
  6. The patient granted her consent for sending two tumor samples to central laboratory for molecular sub study.
  7. Two weeks prior randomization pregnancy test negative for women of childbearing potential.
  8. Women of childbearing potential must use adequate contraceptive measures during participation into study. Oral, injectable or implant hormonal contraceptives measure are not permitted.
  9. A WHO performance status of 0 or 1 ( Karnofsky ³ 80)
  10. Age > 18 years.
  11. Absence of metastases disease
  12. Baseline EKG 12 weeks prior to randomization. Baseline LVEF value within limit of normal value for the institution or > 50% of basal value
  13. Normal laboratory test 2 weeks prior to randomization Haematology values: Neutrophil count ≥ 1,5 x109/l; Platelets ≥ 100 x 109/l; Haemoglobine ≥ 10mg/dl Biochemistry values: serum total bilirubin £ 1 ULN; ASAT (SGOT) y ALAT (SGPT) £ 2,5 ULN; alkaline phosphatase £ 5 ULN. The patients which ASAT and/or ALAT value are > 1,5 ULN along with alkaline phosphatase value > 2,5 ULN will be not included into the study.

    Renal function: serum creatinine £ 175 µmol/l (2 mg/dl). If the value are borderline, clearance creatinine must be ≥ 60 ml/min

  14. 12 weeks prior to randomization the following assessments and procedures must be fulfilled: Bilateral mammography; MRI Breast and axillary; Chest X-Ray (PA and lateral); Abdominal ultrasound; Chest CT-Scan; Abdominal CT-Scan. Bone Scan (if applicable)
  15. Patients must be accessible for treatment and follow up

Exclusion Criteria:

  1. Patients with lumpectomy, partial mastectomy, modified radical mastectomy are not allowed to include into study.
  2. Prior Immunotherapy, hormonal therapy and chemotherapy for breast cancer is not allowed.
  3. Prior therapy with anthracycline and taxanes ( paclitaxel and docetaxel) is not permitted for any neoplasia.
  4. Prior radiotherapy for breast cancer.
  5. Bilateral invasive breast carcinoma
  6. Pregnant or nursing patients. Negative pregnant test ( serum or urine) 14 days prior to randomization.
  7. HER 2 negative breast cancer
  8. Patients of childbearing potential must be use adequate contraceptive measures during study treatment. No hormonal contraceptive measure is permitted.
  9. Any M1 breast cancer
  10. Any motor or sensorial neurotoxicity grade ≥ 2 according to CTC criteria version 3.
  11. Serious cardiac illness or medical conditions: Congestive heart failure, angina pectoris requiring specific treatment, myocardial infarction 1 year prior to enroll in the study; poorly controlled hypertension or high-risk uncontrolled arrhythmias.

    History of significative neurological or psychiatric disease ( psychotic, dementia or attack ) what is unable to patient to grant her informed consent.

    Uncontrolled severe Infection Uncontrolled diabetes mellitus, active peptic ulcer

  12. Current malignancy or previous malignancy other that breast cancer. Exception cell carcinoma of the skin no melanoma, carcinoma in situ of the cervix or any other cancer in the past 10 years.
  13. Long term treatment with corticoids except 6 months prior to inclusion in the study and low doses ( £ 20 mg metilprednisolone or equivalent )
  14. Corticoid use contraindication
  15. Concomitant hormonal replacement therapy. Previous treatment should be interrupted before inclusion into study.
  16. Cardiopathy what stops patient taking Docetaxel and Herceptin: myocardial infarction recorded; angina pectoris requiring specific treatment; any congestive heart failure recorded; arrhythmia grade 3 or 4 according to CTC ver.3; any relevant valvular disease; chest X ray which shows cardiomegaly or EKG which shows ventricular hypertrophy unless FEVI value has been upper URL in the last 3 months.
  17. Poorly controlled hypertension ( systolic > 180 mm Hg or diastolic > 100 mm Hg). The patients with controlled hypertension under treatment can be included into study
  18. Patients under treatment of arrhythmia, angina or congestive heart failure with drug which modifies cardiac conduction (after digital, beta blocker or inhibitors calcium channel) are excluded. However if these drugs are took for arterial tension the patient can be included into study.
  19. The patient must interrupt concomitant treatment with hormonal therapy ej. raloxifen, tamoxifen and selective estrogen receptor modulators (SERM) prior to randomization.
  20. Concomitant use of inhibitors and inductors of enzyme CYP3A4 complex ( ketoconazol, itraconazol or grape juice; rifampicin, carbamazepin or fenitoin ) are not permitted. Also, drug are substrate of enzyme CYP2C8 complex is not permitted along with lapatinib treatment.
  21. Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial within 30 days prior to randomization into study.
  22. Concomitant treatment with other anticancer therapy
  23. Hypersensitivity reaction to drugs herceptin, lapatinib or their excipients.
  24. Male
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00841828

Locations
Spain
Hospital Germans Trias i Pujol
Badalona, Badalona/Barcelona, Spain, 08916
Hospital General de Granollers
Granollers, Barcelona, Spain, 08400
Xarxa Asistencial de Manresa
Manresa, Barcelona, Spain, 08243
Corporación Sanitaria Parc Taulí
Sabadell, Barcelona, Spain, 08208
Hospital del Espíritu Santo
Santa Coloma de Gramanet, Barcelona, Spain, 08923
Hospital Mutua de Terrasa
Tarrasa, Barcelona, Spain, 08221
Consorci Sanitari de Terrasa
Tarrasa, Barcelona, Spain, 08221
Hospital Xeral Cíes
Vigo, Pontevedra, Spain, 36204
Hospital Universitario de Canarias
La Laguna, Santa Cruz de Tenerife, Spain, 38320
Complejo Hospitalario Universitario A Coruña
A Coruña, Spain, 15006
Centro Oncológico de Galicia
A Coruña, Spain, 15009
Hospital Clinic i Provincial
Barcelona, Spain, 08036
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08041
Hospital del Mar
Barcelona, Spain, 08003
Hospital General Yagüe
Burgos, Spain, 09005
Complejo Hospitalario San Pedro de Alcántara
Cáceres, Spain, 10003
Hospital Provincial de Córdoba
Córdoba, Spain, 14004
Complejo Hospitalario de Jaén
Jaén, Spain, 23007
Hospital de la Princesa
Madrid, Spain, 28006
Hospital Universitario Virgen de la Victoria
Málaga, Spain, 29010
Hospital Central de Asturias
Oviedo, Spain, 33006
Instituto Oncológico de Guipúzcoa
San Sebastián, Spain, 20012
Hospital Virgen de la Salud
Toledo, Spain, 45004
Hospital Universitario La Fe
Valencia, Spain, 46009
Hospital Clinico de Valencia
Valencia, Spain, 46010
Instituto Valenciano de Oncología
Valencia, Spain, 46009
Hospital Miguel Servet
Zaragoza, Spain, 50009
Sponsors and Collaborators
Spanish Breast Cancer Research Group
GlaxoSmithKline
Investigators
Study Director: Ana Lluch, PhD., MD. Hospital Clínico de Valencia. Av. Blasco Ibáñez, 17. 46010 Valencia.
Study Director: Emilio Alba, PhD., MD. Hospital Virgen de la Victoria. Campus de Teatinos, s/n. 29010 Málaga
Study Director: Joan Albanell, PhD., MD. Hospital del Mar. Paseo Marítimo, 25-29. 08003 Barcelona
  More Information

Additional Information:
No publications provided

Responsible Party: Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT00841828     History of Changes
Other Study ID Numbers: GEICAM/2006-14, Nº EudraCT 2007-007031-13
Study First Received: February 9, 2009
Last Updated: June 7, 2013
Health Authority: Spain: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Docetaxel
Trastuzumab
Lapatinib
Epirubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014