Combination Therapy With MYOCET® (Doxorubicin HCL Liposome for Injection) in Participants With HER2-Positive Breast Cancer

NCT00712881 | Completed Phase 2 Results

• 2 other identifiers: C19562/20372008-000709-12
• Study Type: interventional
• Target: 126
• Locations: 6 countries
• Sites: 22

Brief 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 (HER2) gene.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 .

  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

  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)

  Baseline up to the end of Cycle 8 (each cycle length = 21 days)

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

  Baseline, up to 5 years

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Baseline up to the end of Cycle 8 (cycle length = 21 days)

• Percentage of Participants With Progression or Death

  Up to 5 Years after randomization

Study Arms (2)

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 \[6 mg/kg\]).

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.

Drug: Cyclophosphamide; Drug: Trastuzumab; Drug: Free doxorubicin hydrochloride; Drug: Docetaxel

Interventions

Liposomal doxorubicin hydrochloride DRUG

Liposomal doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.

Also known as: Myocet®

Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH)

Cyclophosphamide DRUG

Cyclophosphamide will be administered per dose and schedule specified in the arm description.

Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH); Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH)

Trastuzumab DRUG

Trastuzumab will be administered per dose and schedule specified in the arm description.

Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH); Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH)

Free doxorubicin hydrochloride DRUG

Free doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.

Also known as: Anthracycline

Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH)

Docetaxel DRUG

Docetaxel will be administered per dose and schedule specified in the arm description.

Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH); Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Cephalon, Inc.: lead

Study Sites (22)

Teva Investigational Site 16

Kufstein, Austria

Location

Teva Investigational Site 15

Vienna, Austria

Location

Teva Investigational Site 9

Brussels, Belgium

Location

Teva Investigational Site 29

Yvoir, Belgium

Location

Teva Investigational Site 4

Clichy, France

Location

Teva Investigational Site 5

Nancy, France

Location

Teva Investigational Site 33

Reims, France

Location

Teva Investigational Site 8

Vandœuvre-lès-Nancy, France

Location

Teva Investigational Site 30

Aachen, Germany

Location

Teva Investigational Site 11

Düsseldorf, Germany

Location

Teva Investigational Site 25

Düsseldorf, Germany

Location

Teva Investigational Site 32

Essen, Germany

Location

Teva Investigational Site 34

Loerrach, Germany

Location

Teva Investigational Site 14

München, Germany

Location

Teva Investigational Site 27

München, Germany

Location

Teva Investigational Site 20

Napoli, Italy

Location

Teva Investigational Site 23

Roma, Italy

Location

Teva Investigational Site 21

Verona, Italy

Location

Teva Investigational Site 26

Barcelona, Spain

Location

Teva Investigational Site 3

Barcelona, Spain

Location

Teva Investigational Site 1

Lleida, Spain

Location

Teva Investigational Site 2

Zaragoza, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Trastuzumab; Anthracyclines; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2008
• First Posted: July 10, 2008
• Study Start: October 13, 2008
• Primary Completion: September 17, 2015
• Study Completion: September 17, 2015
• Last Updated: February 23, 2024
• Results First Posted: February 23, 2024

Record last verified: 2023-07

Locations

FR (4); BE (2); IT (3); DE (7); AU (2); ES (4)