Breast CancerPhase 2NCT00712881
Combination Therapy With MYOCET® (Doxorubicin HCL Liposome for Injection) in Participants With HER2-Positive Breast Cancer
A Phase 2 study testing Liposomal doxorubicin hydrochloride, Cyclophosphamide and Trastuzumab in people with Breast Cancer, run by Cephalon, Inc. at 22 sites in 6 countries.
Trial summary
To evaluate the efficacy and safety of treatment with MYOCET® (doxorubicin hydrochloride) in combination with cyclophosphamide and trastuzumab, 4 cycles, followed by docetaxel plus trastuzumab, 4 cycles, in women with stage II or III breast cancer whose tumour overexpresses the human epidermal growth factor receptor 2… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Liposomal doxorubicin hydrochloride, Cyclophosphamide and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 22 sitesin 6 countries
- Study dates
- 13 Oct 2008to 17 Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria:
- Treatment-naive participants with stage II or III invasive breast cancer (proven histologically/cytologically) and with tests showing an overexpressing of HER2.
- Participants have at least 1 bidimensionally measurable lesion according to the World Health Organization (WHO) criteria.
- The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- The participant has an LVEF of at least 55% as assessed by multigated acquisition (MUGA) scan (preferred) or echocardiography.
- The participant has hematology and serum chemistry laboratory test results within specific protocol-defined ranges.
- Women of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the treatment period and for 6 months after the last administration of study drug.
Main Exclusion Criteria:
The participant:
- Has received previous cancer therapy for breast cancer.
- Has any history of CHF, angina pectoris, or myocardial infarction.
- Has uncontrolled hypertension.
- Has infection, peptic ulcer, or unstable diabetes mellitus.
- Has been treated with live virus vaccines within 8 weeks before the first administration of study drug.
- Has impaired hepatic or renal function.
- Is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
- Has used an investigational drug within one month before the screening visit.
- Has a known hypersensitivity to any of the study drugs or to their active ingredients.
- Has an inflammatory breast cancer.
- Has had any other malignancies within five years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
Note: Other inclusion and exclusion criteria may apply.
Trial locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
Germany7 sites
Teva Investigational Site 30
Aachen
Teva Investigational Site 11
Düsseldorf
Teva Investigational Site 25
Düsseldorf
Teva Investigational Site 32
Essen
Teva Investigational Site 34
Loerrach
Teva Investigational Site 14
München
Teva Investigational Site 27
München
France4 sites
Teva Investigational Site 4
Clichy
Teva Investigational Site 5
Nancy
Teva Investigational Site 33
Reims
Teva Investigational Site 8
Vandœuvre-lès-Nancy
Spain4 sites
Teva Investigational Site 26
Barcelona
Teva Investigational Site 3
Barcelona
Teva Investigational Site 1
Lleida
Teva Investigational Site 2
Zaragoza
Italy3 sites
Teva Investigational Site 20
Naples
Teva Investigational Site 23
Roma
Teva Investigational Site 21
Verona
Austria2 sites
Teva Investigational Site 16
Kufstein
Teva Investigational Site 15
Vienna
Belgium2 sites
Teva Investigational Site 9
Brussels
Teva Investigational Site 29
Yvoir
About this study
Official title: Prospective, Open-Label, Randomized Study of Combination Therapy of MYOCET® Plus Cyclophosphamide and Trastuzumab Versus Free Doxorubicin Plus Cyclophosphamide Alone, Each Followed by Docetaxel and Trastuzumab, in Neoadjuvant Setting in Treatment-Naive Patients With HER2-Positive Breast Cancer
To evaluate the efficacy and safety of treatment with MYOCET® (doxorubicin hydrochloride) in combination with cyclophosphamide and trastuzumab, 4 cycles, followed by docetaxel plus trastuzumab, 4 cycles, in women with stage II or III breast cancer whose tumour overexpresses the human epidermal growth factor receptor 2 (HER2) gene.
- Conditions
- Breast Cancer
- Being tested
- Liposomal doxorubicin hydrochloride, Cyclophosphamide, Trastuzumab, Free doxorubicin hydrochloride, Docetaxel
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal doxorubicin hydrochlorideDrug
Also called Myocet®
Liposomal doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.
CyclophosphamideDrug
Cyclophosphamide will be administered per dose and schedule specified in the arm description.
TrastuzumabDrug
Trastuzumab will be administered per dose and schedule specified in the arm description.
Free doxorubicin hydrochlorideDrug
Also called Anthracycline
Free doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.
DocetaxelDrug
Docetaxel will be administered per dose and schedule specified in the arm description.
| Study group | Role | What they receive |
|---|---|---|
| Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) | Experimental | Participants will receive MCH (liposomal doxorubicin hydrochloride [60 milligrams {mg}/square meter {m^2}], cyclophosphamide (600 mg/m^2), and trastuzumab (8 or 6 mg/kilogram {kg}), administered as intravenous (IV) infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab will be 8 mg/kg; 6 mg/kg will be used for the remaining cycles. After 4 cycles of MCH, the treatment will be changed to 4 consecutive 21-day cycles of TH (docetaxel [100 mg/m^2] and trastuzumab [6 mg/kg]). Receives: Drug: Liposomal doxorubicin hydrochloride; Drug: Cyclophosphamide; Drug: Trastuzumab; Drug: Docetaxel |
| Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) | Active comparator | Participants will receive AC (free doxorubicin hydrochloride [60 mg/m^2] and cyclophosphamide [600 mg/m^2]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment will be changed to 4 consecutive 21-day cycles of TH (docetaxel [100 mg/m^2] and trastuzumab [8 or 6 mg/kg]). For the first cycle, the loading dose of trastuzumab will be 8 mg/kg; 6 mg/kg will be used for the remaining cycles. Receives: Drug: Cyclophosphamide; Drug: Trastuzumab; Drug: Free doxorubicin hydrochloride; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Exhibiting a Pathological Complete Response (pCR) in Breast
The pCR of breast was based upon histologic examination, as confirmed by a central panel of experts, of resected tissue .
Measured: At the end of Cycle 8 (each cycle length = 21 days)
Secondary outcomes (8)
Percentage of Participants Who Achieved an Objective Response (Complete Response [CR] or Partial Response [PR]), as Defined by World Health Organization (WHO) Guidelines
CR: Disappearance of the lesions and no new lesions. In case of bone metastasis a CR is represented by the normalization of radiography or the complete sclerotic healing of lytic area.
PR: In the case of bidimensionally measurable lesions/tumors, a decrease by at least 50% of the sum of the products of the largest perpendicular diameters of each individual lesion/tumor. In the case of unidimensionally measurable lesions a decrease by at least 50% in the largest linear tumour measurement. In the case of non-measurable but evaluable lesions an appreciable change of lesions referable to disease improvement. For bone lesions partial decrease in size or recalcification of lytic areas. No lesion should have progressed and no new lesion should appear.
Measured: At the end of Cycle 8 (each cycle length = 21 days)
Percentage of Participants With Class III or IV New York Health Association (NYHA) Congestive Heart Failure (CHF)
Occurrence of Class III or IV (NYHA) CHF has been reported. Class III: Participants with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV: Participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Measured: Baseline up to the end of Cycle 8 (each cycle length = 21 days)
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
The LVEF is a fraction of blood (in percent) pumped out of the left ventricle of the heart (the main pumping chamber). LVEF was measured using multigated acquisition (MUGA) or echocardiography.
Measured: Baseline, up to 5 years
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. The TEAE was an AE that began or worsened after treatment with study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Measured: Baseline up to the end of Cycle 8 (cycle length = 21 days)
Percentage of Participants With Progression or Death
Progression was defined as a 25% or more increase in the size of the lesion or appearance of new lesion. If the participant did not develop an event (disease progression or death), the participant was censored at the last known tumor assessment date (or last follow-up visit without progression documented).
Measured: Up to 5 Years after randomization
Percentage of Participants Achieving a Pathological Complete Response (pCR) in Breast and Node
The pCR of breast and node was based upon histologic examination, as confirmed by a central panel of experts, of breast tissue resected.
Measured: At the end of Cycle 8 (each cycle length = 21 days)
Number of Participants Undergoing Breast Conservative Surgery
Measured: At the end of Cycle 8 (each cycle length = 21 days)
Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
AEs were recorded and graded per the NCI CTCAE scale. The NCI CTCAE is a toxicity scale used to grade the severity of adverse events experienced with cancer treatment. Grade 1= Mild; Grade 2= Moderate; Grade 3= Severe; Grade 4= Life-threatening or disabling; Grade 5= Death related to AE. For summaries for the toxicity grade, participants were counted once at the greatest NCI CTCAE grade.
Measured: Up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2008 (estimated)
- Study start13 Oct 2008
- Primary completion17 Sep 2015
- Study completion17 Sep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cephalon, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Teva Medical Expert, Study director, Teva Branded Pharmaceutical Products R&D, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00712881
- Sponsor's protocol ID
- C19562/2037
- Other IDs
- 2008-000709-12, 2008
- Status last verified
- Jul 2023
- First submitted
- 8 Jul 2008
- Last updated
- 23 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open-Label, Randomized Study of Combination Therapy of MYOCET® Plus Cyclophosphamide and Trastuzumab Versus Free Doxorubicin Plus Cyclophosphamide Alone, Each Followed by Docetaxel and Trastuzumab, in Neoadjuvant Setting in Treatment-Naive Patients With HER2-Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT00712881
- Acronym / sponsor ID
- C19562/2037
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- Cephalon, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Oct 2008 (actual)
- Primary completion
- 17 Sep 2015 (actual)
- Study completion
- 17 Sep 2015 (actual)
- First posted
- 10 Jul 2008 (estimated)
- Results
- Posted 23 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the efficacy and safety of treatment with MYOCET® (doxorubicin hydrochloride) in combination with cyclophosphamide and trastuzumab, 4 cycles, followed by docetaxel plus trastuzumab, 4 cycles, in women with stage II or III breast cancer whose tumour overexpresses the human epidermal growth factor receptor 2 (HER2) gene.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) | Experimental | Drug: Liposomal doxorubicin hydrochloride, Drug: Cyclophosphamide, Drug: Trastuzumab, Drug: DocetaxelParticipants will receive MCH (liposomal doxorubicin hydrochloride [60 milligrams {mg}/square meter {m^2}], cyclophosphamide (600 mg/m^2), and trastuzumab (8 or 6 mg/kilogram {kg}), administered as intravenous (IV) infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab will be 8 mg/kg; 6 mg/kg will be used for the remaining cycles. After 4 cycles of MCH, the treatment will be changed to 4 consecutive 21-day cycles of TH (docetaxel [100 mg/m^2] and trastuzumab [6 mg/kg]). |
| Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) | Active comparator | Drug: Cyclophosphamide, Drug: Trastuzumab, Drug: Free doxorubicin hydrochloride, Drug: DocetaxelParticipants will receive AC (free doxorubicin hydrochloride [60 mg/m^2] and cyclophosphamide [600 mg/m^2]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment will be changed to 4 consecutive 21-day cycles of TH (docetaxel [100 mg/m^2] and trastuzumab [8 or 6 mg/kg]). For the first cycle, the loading dose of trastuzumab will be 8 mg/kg; 6 mg/kg will be used for the remaining cycles. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal doxorubicin hydrochlorideAlso: Myocet®Liposomal doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description. | Drug | Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) |
| CyclophosphamideCyclophosphamide will be administered per dose and schedule specified in the arm description. | Drug | Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH), Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) |
| TrastuzumabTrastuzumab will be administered per dose and schedule specified in the arm description. | Drug | Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH), Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) |
| Free doxorubicin hydrochlorideAlso: AnthracyclineFree doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description. | Drug | Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) |
| DocetaxelDocetaxel will be administered per dose and schedule specified in the arm description. | Drug | Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH), Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) |
Primary outcome
Percentage of Participants Exhibiting a Pathological Complete Response (pCR) in Breast
Time frame: At the end of Cycle 8 (each cycle length = 21 days)
The pCR of breast was based upon histologic examination, as confirmed by a central panel of experts, of resected tissue .
8 secondary outcomes
Percentage of Participants Who Achieved an Objective Response (Complete Response [CR] or Partial Response [PR]), as Defined by World Health Organization (WHO) Guidelines
Time frame: At the end of Cycle 8 (each cycle length = 21 days)
Percentage of Participants With Class III or IV New York Health Association (NYHA) Congestive Heart Failure (CHF)
Time frame: Baseline up to the end of Cycle 8 (each cycle length = 21 days)
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline, up to 5 years
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Baseline up to the end of Cycle 8 (cycle length = 21 days)
Percentage of Participants With Progression or Death
Time frame: Up to 5 Years after randomization
Percentage of Participants Achieving a Pathological Complete Response (pCR) in Breast and Node
Time frame: At the end of Cycle 8 (each cycle length = 21 days)
Number of Participants Undergoing Breast Conservative Surgery
Time frame: At the end of Cycle 8 (each cycle length = 21 days)
Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Time frame: Up to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teva Medical Expert study director
Teva Branded Pharmaceutical Products R&D, Inc.
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liposomal doxorubicin hydrochloride, Cyclophosphamide and Trastuzumab in people with Breast Cancer, run by Cephalon, Inc. at 22 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Germany, France, Spain, Italy, Austria and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Exhibiting a Pathological Complete Response (pCR) in Breast (time frame: At the end of Cycle 8 (each cycle length = 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.