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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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25 November 2019 |
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Main ID: |
EUCTR2008-002819-40-GB |
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Date of registration:
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31/10/2008 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A randomized, multicenter, Phase II study of the efficacy and safety of trastuzumab-MCC-DM1 vs. trastuzumab (Herceptin®) and docetaxel (Taxotere®) in patients with metastatic HER2-positive breast cancer who have not received prior chemotherapy for metastatic disease
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Scientific title:
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A randomized, multicenter, Phase II study of the efficacy and safety of trastuzumab-MCC-DM1 vs. trastuzumab (Herceptin®) and docetaxel (Taxotere®) in patients with metastatic HER2-positive breast cancer who have not received prior chemotherapy for metastatic disease |
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Date of first enrolment:
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18/03/2009 |
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Target sample size:
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120 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002819-40 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: yes
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Austria
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Belgium
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Germany
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Hungary
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Italy
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Spain
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
a. Disease-Specific Criteria
1. Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy. Patients with locally advanced disease must have recurrent or progressive disease after failing initial attempts at local control. The disease must be considered to be unresectable.
2. HER2-positive (IHC 3+ or FISH-positive) based on local laboratory assay results
3. No prior chemotherapy for their MBC. (Hormonal therapy is allowed.)
4. Measurable disease per modified RECIST
Patients should have at least one target lesion =2cm on conventional CT scan or = 1cm on a spinal CT scan.
5. Tumor blocks or 11 unstained slides available for confirmatory central laboratory HER2 testing
b. General Criteria
6. Age =18 years
7. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1
8. Adequate organ function, evidenced by the following laboratory results within approximately 21 days prior to randomization:
9. Absolute neutrophil count >1500 cells/mm[3]
Platelet count > 100,000 cells/mm[3]
Hemoglobin > 9.0 g/dL
Patients are allowed to be transfused with red blood cells to obtain this level
Total bilirubin = 1.5 x the upper limit of normal (ULN)
SGOT (AST), SGPT (ALT) and alkaline phophatase =2.5 ×ULN
following exception:
Patients with hepatic and/or bone metastases: alkaline phosphatase =5 ×ULN
Serum Creatinine < 1.5 × ULN
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) < 1.5 ×ULN (unless on therapeutic anticoagulation or due a lupus anticoagulant)
10. For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the study. Specific country requirements will be followed (e.g., in the United Kingdom, women of childbearing potential and male subjects and their partners of childbearing potential must use two methods of contraception [one of which must be a barrier method] for the duration of the study).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
a. Cancer-Related Criteria
1. History of any chemotherapy for MBC
Prior hormonal therapy is allowed
2. An interval of <6 months from the completion of cytotoxic chemotherapy (excluding hormonal therapy) in the neo-adjuvant or adjuvant setting until the time of metastatic diagnosis. Patients who progress on or within 12 months on single-agent trastuzumab will be considered eligible (unless trastuzumab has been given = 21 days prior to randomization).
3. Trastuzumab = 21 days prior to randomization
4. Hormone therapy < 7 days prior to randomization
5. Current peripheral neuropathy of Grade =3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0
6. History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned.
7. Previous radiotherapy for the treatment of unresectable, locally advanced or metastatic breast cancer is not allowed if:
More than 25% of marrow-bearing bone has been irradiated.
The last fraction of radiotherapy has been administered within approximately 3 weeks prior to randomization.
8. Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to randomisation. CT or magnetic resonance imaging (MRI) scan of the brain is mandatory (within approximately 28 days prior to randomization) in cases of clinical suspicion of brain metastases or in a patient with any prior history of brain metastases.
9. History of exposure to the following cumulative doses of anthracyclines:
Doxorubicin or liposomal doxorubicin > 500 mg/m[2]
Epirubicin > 900 mg/m[2]
Mitoxantrone > 120mg/m[2] and idarubicin > 90 mg/m[2]
If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m[2] of doxorubicin.
b. Cardiopulmonary Function
10. Current unstable angina
11. History of symptomatic congestive heart failure (CHF; New York Heart Association [NYHA] classes II-IV), or ventricular arrhythmia requiring treatment
12. History of myocardial infarction within 6 months prior to randomization
13. LVEF below 50% within approximately 28 days prior to randomization
14. History of decrease in LVEF <40% or symptomatic CHF with previous adjuvant trastuzumab treatment
15. Cardiac troponin I = 0.2 ng/mL within approximately 28 days prior to randomization
16. Severe dyspnea at rest because of complications of advanced malignancy or requiring current continuous oxygen therapy
General Criteria
17. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)
18. Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation o
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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HER2-positive metastatic breast cancer
MedDRA version: 9.1
Level: LLT
Classification code 10027475
Term: Metastatic breast cancer
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Intervention(s)
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Product Name: Trastuzumab-MCC-DM1
Product Code: T-DM1, RO05304020
Pharmaceutical Form: Powder for concentrate for solution for infusion
CAS Number: 1018448-65-1
Current Sponsor code: RO05304020
Other descriptive name: T-DM1
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 160-172
Trade Name: Herceptin 150 mg Powder for concentrate for solution for infusion
Pharmaceutical Form: Powder for concentrate for solution for infusion
Other descriptive name: TRASTUZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Trade Name: TAXOTERE 80 mg concentrate and solvent for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 114977-28-5
Other descriptive name: DOCETAXEL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-
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Primary Outcome(s)
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Secondary Objective: The secondary objectives of this study are as follows:
• To explore the efficacy of T-DM1 compared with the combination of trastuzumab and docetaxel in patients with HER2-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease, as measured by the 12-month PFS rate, median PFS, duration of overall survival, survival rate at 12 months, objective response rate, duration of objective response, and clinical benefit rate (the proportion of patients with CR or PR or stable disease at greater than 6 months since randomisation)
• To characterize the PK properties of T-DM1 in this patient population
• To compare the time to symptom progression, as measured by the Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) and the Patient's Assessment of Pain in the two treatment arms
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Primary end point(s): The primary efficacy endpoint for this study is PFS, defined as the time from randomization to the first occurrence of disease progression, as determined by investigator tumor assessments using RECIST, or death on study from any cause. Death on study is defined as death from any cause within 30 days of the last dose of study drug prior to crossover.
The first documented PD event prior to crossover in the control arm will be included in the analysis of the primary endpoint of PFS.
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Main Objective: The primary objectives for this study are as follows:
• To explore the efficacy of T-DM1 compared with the combination of trastuzumab and docetaxel in patients with HER2-positive, unresectable, locally advanced breat cancer and/or metastatic breat cancer who have not received prior chemotherapy for metastatic disease, as measured by PFS based on investigator assessments
• To evaluate the safety of T-DM1 compared with the combination of trastuzumab and docetaxel in this population
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Secondary ID(s)
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2008-002819-40-DE
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TDM4450g
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date:
Contact:
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