ClinicalTrials.gov
ClinicalTrials.gov Menu

EC Followed Docetaxel VS ET Followed Capecitabine as Adjuvant Chemotherapy for Node Positive Operable Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00129935
Recruitment Status : Active, not recruiting
First Posted : August 12, 2005
Last Update Posted : March 19, 2018
Sponsor:
Collaborators:
Sanofi
Hoffmann-La Roche
Pfizer
Information provided by (Responsible Party):
Spanish Breast Cancer Research Group

Brief Summary:

This is a prospective, randomised phase III trial, to compare the efficacy and safety profiles of two types of adjuvant chemotherapy regimens for HER2 negative, node positive breast cancer patients.

Control Arm: This includes 4 cycles of EC 90/600 mg/m2 day 1 every 3 weeks, followed by 4 cycles of T 100 mg/m2 day 1 every 3 weeks.

Experimental Arm: This includes 4 cycles of ET 90/75 mg/m2, day 1 every 3 weeks, followed by 4 cycles of capecitabine 1250 mg/m2, twice a day, via oral intake, for 14 days, and then a one-week rest period.

Premenopausal women with hormone receptor positive tumours must receive 5 years of tamoxifen after the end of chemotherapy.

Postmenopausal women with hormone receptor positive tumours can receive tamoxifen or aromatase inhibitors (or both) after the end of chemotherapy.

Patients may receive radiotherapy when clinically indicated.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Docetaxel Drug: Capecitabine Phase 3

Detailed Description:
Estimation of the 5-year disease-free survival in the control arm is 72%. The experimental arm is expected to increase the 5-year disease-free survival by 7% (up to 79%). With an alpha error of 0.05 and 80% power, 592 patients per arm are needed. Assuming a 17% post-randomization drop-out, 691 patients per arm are needed.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1384 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Trial to Compare Epirubicin and Cyclophosphamide (EC) Followed by Docetaxel (T) to Epirubicin and Docetaxel (ET) Followed by Capecitabine (X) as Adjuvant Treatment, Node Positive Breast Cancer Patients
Actual Study Start Date : February 2004
Actual Primary Completion Date : January 2013
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: EC followed Docetaxel
Epirubicin 90 mg/ m2 in combination with cyclophosphamide 600 mg/m2 (EC) every 21 days for 4 cycles, followed by docetaxel 100 mg/m2 (T) every 21 days for 4 cycles.
Drug: Docetaxel
Docetaxel 100 mg/m2 every 21 days for 4 cycles (control Arm).
Other Names:
  • Doxorubicin
  • Cyclophosphamide

Drug: Capecitabine
Docetaxel 75 mg/ m2 every 21 days for 4 cycles (experimental Arm)
Other Names:
  • Doxorubicin
  • Docetaxel

Experimental: ET followed Capecitabine
Epirubicin 90 mg/m2 and docetaxel 75 mg/ m2 (ET) every 21 days for 4 cycles, followed by capecitabine 1,250 mg/m2 bid for 14 days, followed by a 7-day rest for 4 cycles.
Drug: Docetaxel
Docetaxel 100 mg/m2 every 21 days for 4 cycles (control Arm).
Other Names:
  • Doxorubicin
  • Cyclophosphamide

Drug: Capecitabine
Docetaxel 75 mg/ m2 every 21 days for 4 cycles (experimental Arm)
Other Names:
  • Doxorubicin
  • Docetaxel




Primary Outcome Measures :
  1. disease-free survival [ Time Frame: 5 years ]
    To compare the disease-free survival between both treatment arms


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 10 years ]
    Time until the date of death for any reason.

  2. Toxicity [ Time Frame: 5 years ]
    To evaluate Adverse Events using NCI-CTC criteria

  3. Quality of life [ Time Frame: 5 years ]
    Through quality of life questionnaires that are collected along the study

  4. Single nucleotide polymorphisms (SNPs) as treatment predictive factors [ Time Frame: 5 years ]
    Study individual and intratumoral molecular changes (immunohistochemical expression, mutation and amplification of specific genes), which may be responsible for the individual distribution to the response

  5. Molecular prognostic markers in tissue [ Time Frame: 5 years ]
    Study individual and intratumoral molecular changes (immunohistochemical expression, mutation and amplification of specific genes), which may be responsible for the individual distribution to the response



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent.
  • Histological diagnosis of operable invasive adenocarcinoma of the breast (T1-T3). Tumours must be HER2 negative. Time window between surgery and study randomization must be less than 60 days.
  • Surgery must consist of mastectomy or conservative surgery with axillary lymph node dissection. Margins free of disease and ductal carcinomas in situ (DCIS) are required. Lobular carcinoma is not considered a positive margin.
  • Positive axillary lymph nodes defined as at least 1 out of 10 nodes with presence of disease. If sentinel node technique is used, sentinel node can be the only node affected. Patients belonging to the following classifications are eligible: pN1a, pN2a, pN3a.
  • Status of hormone receptors in primary tumour. Results must be available before the end of adjuvant chemotherapy.
  • Patients must not present evidence of metastatic disease. Status of HER2 in primary tumour, known before randomization. Patients with immune histochemistry (IHC) 0 or +1 are eligible. For patients with ICH 2+, fluorescence in situ hybridization (FISH) is mandatory and result must be negative.
  • Age >= 18 and <= 70 years old.
  • Performance status (Karnofsky index) >= 80.
  • Normal electrocardiogram (EKG) in the 12 weeks prior to randomization. If needed, normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF).
  • Laboratory results (within 14 days prior to randomization):

    • Hematology: neutrophils >= 1.5 x 10^9/l; platelets >= 100 x 10^9/l; hemoglobin >= 10 mg/dl;
    • Hepatic function: total bilirubin <= 1 upper normal limit (UNL); SGOT and SGPT <= 2.5 UNL; alkaline phosphatase <= 2.5 UNL. If values of SGOT and SGPT > 1.5 UNL are associated to alkaline phosphatase > 2.5 UNL, patient is not eligible;
    • Renal function: creatinine <= 175 mmol/l (2 mg/dl); creatinine clearance >= 60 ml/min;
    • Pharmacogenetics: one blood sample is needed for SNP assessment.
  • Complete stage workup during the 12 weeks prior to randomization (mammograms are allowed within a 20 week window). All patients must have a bilateral mammogram, thorax x-ray, abdominal echography and/or computed tomography (CT)-scan. If bone pain, and/or alkaline phosphatase elevation, a bone scintigraphy is mandatory. This test is recommended for all patients. Other tests: as clinically indicated.
  • Patients able to comply with treatment and study follow-up.
  • Negative pregnancy test done in the 14 prior days to randomization.

Exclusion Criteria:

  • Prior systemic therapy for breast cancer.
  • Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any malignancy.
  • Prior radiotherapy for breast cancer.
  • Bilateral invasive breast cancer.
  • Pregnant or lactating women. Adequate contraceptive methods must be used during chemotherapy and hormone therapy treatments.
  • Any T4 or M1 tumour.
  • Axillary lymph nodes: patients belonging to the following classifications are excluded: pN1b, pN1c, pN2b, pN3b, pN3c.
  • HER2 positive breast cancer (IHC 3+ or positive FISH result).
  • Pre-existing grade >= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria version 2.0 [NCI CTC v-2.0]).
  • Any other serious medical pathology, such as congestive heart failure; unstable angina; history of myocardial infarction during the previous year; uncontrolled HA or high risk arrhythmias.
  • History of neurological or psychiatric disorders, which could preclude the patients from free informed consent.
  • Active uncontrolled infection.
  • Active peptic ulcer; unstable diabetes mellitus.
  • Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumour 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 corticosteroid administration.
  • Concomitant treatment with raloxifene, tamoxifen or other selective estrogen receptor modulators (SERMs), either for osteoporosis treatment or for prevention. These treatments must stop before randomisation.
  • Concomitant treatment with other investigational products; participation in other clinical trials with a non-marketed drug in the 20 previous days before randomization.
  • Concomitant treatment with another therapy for cancer.
  • Males.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00129935


  Show 58 Study Locations
Sponsors and Collaborators
Spanish Breast Cancer Research Group
Sanofi
Hoffmann-La Roche
Pfizer
Investigators
Study Director: Study Director Hospital Clínico Universitario San Carlos

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT00129935     History of Changes
Other Study ID Numbers: GEICAM 2003-10
First Posted: August 12, 2005    Key Record Dates
Last Update Posted: March 19, 2018
Last Verified: March 2018

Keywords provided by Spanish Breast Cancer Research Group:
HER2 negative breast cancer
Node positive breast cancer
Adjuvant treatment
Oral chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Docetaxel
Liposomal doxorubicin
Capecitabine
Doxorubicin
Epirubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors