MYOHERTAX: Liposomal Doxorubicin, Trastuzumab, and Docetaxel in HER2 Positive Metastatic Breast Cancer

Sponsor

Laurence J.C. van Warmerdam (Other)

Overall Status

Terminated

CT.gov ID

NCT00377780

Collaborator

Cephalon (Industry), Sanofi (Industry)

Enrollment

Locations

Arm

108

Duration (Months)

8.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open phase II study evaluating the efficacy and safety of the non pegylated liposomal doxorubicin (Myocet®), trastuzumab (Herceptin®), and docetaxel (Taxotere®) combination as first-line treatment of patients with metastatic HER2/neu positive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Neoplasm Metastasis	Drug: Non pegylated liposomal doxorubicin, trastuzumab, docetaxel	Phase 2

Detailed Description

Phase II non comparative study, assessing the safety (primarily cardiac safety) and efficacy in patients with locally advanced or metastatic HER2/neu positive breast cancer not yet treated with chemotherapy for metastatic disease.

Myocet and Taxotere will be given for a maximum of 6 cycles, Herceptin treatment for 1 year is recommended.

Endpoints: cardiotoxicity (left ventricular ejection fraction decrease and/or symptoms of heart failure), serious other toxicity, disease progression.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Multicentre Open Label Study Evaluating the Efficacy and Safety of Liposomal Doxorubicin, Trastuzumab, Docetaxel as First-line Treatment of Patients With HER2 Positive Metastatic Breast Cancer

Study Start Date :

Aug 1, 2006

Actual Primary Completion Date :

Aug 1, 2015

Actual Study Completion Date :

Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Myocet + docetaxel + trastuzumab	Drug: Non pegylated liposomal doxorubicin, trastuzumab, docetaxel max. 6 courses Other Names: Myocet, herceptin, toxotere

Arm

Intervention/Treatment

Experimental: 1

Myocet + docetaxel + trastuzumab

Drug: Non pegylated liposomal doxorubicin, trastuzumab, docetaxel

max. 6 courses

Other Names:

Myocet, herceptin, toxotere

Outcome Measures

Primary Outcome Measures

Cardiotoxicity (definite or probable cardiac death) [treatment period]
Signs or symptoms of congestive heart failure (CHF), New York Heart Association (NYHA) class III-IV [treatment period]
Decline in left ventricular ejection fraction (LVEF) of ≥ 5% to < 50% with mild signs or symptoms of CHF (NYHA class < III) [treatment period]
Decline in LVEF of ≥ 10% to < 50% without signs or symptoms of CHF [treatment period]

Secondary Outcome Measures

Frequency and severity of intercurrent events according to the National Cancer Institute - Common Terminology Criteria (NCI-CTC) classification [treatment period]
Response rate [treatment period]
Median time to progression [treatment period]
Progression free survival [treatment period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Women with histologically documented metastatic or locally advanced metastatic HER2/neu positive breast cancer at 1st line of palliative chemotherapy.
In the case of previous adjuvant or neoadjuvant chemotherapy with anthracyclines or taxanes, this must have been completed more than 12 months before inclusion.
In the case of previous adjuvant or neoadjuvant chemotherapy, cumulative anthracycline dose ≤ 240 mg/m2 of doxorubicin or 450 mg/m2 of epirubicin or 75 mg/m2 of mitoxantrone on inclusion.
Previous endocrine therapy is authorized (endocrine therapy other than goserelin must be stopped before starting treatment).
Previous radiotherapy is authorized, if discontinued ≥ 4 weeks prior to inclusion in the study and if < 10% of the bone marrow was within the irradiated area.
Age ≥ 18 years.
Performance status 0,1, or 2.
Life expectancy ≥ 3 months.
Evaluable disease.
Normal LVEF (multigated acquisition [MUGA] scan or echocardiography).
Normal haematological, hepatic and renal parameters: neutrophils ≥ 1.5 x 10^{9/l;
platelets ≥ 100 x 10}9/l; hemoglobin (Hb) ≥ 6 mmol/L; total bilirubin ≤ 1.5 times the upper limit of normal (ULN); transaminases ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 x ULN; creatinine ≤ 1.5 x ULN.
Dated and signed written informed consent.

Exclusion Criteria:

Previous chemotherapy for metastatic disease.
History of other cancer, except for cervical carcinoma in situ treated by cone resection or basal cell or squamous cell skin cancer.
History of congestive heart failure or myocardial infarction ≤ 1 year; cardiac function: NYHA ≥ 2 or LVEF < 50%.
Uncontrolled significant heart disease, such as unstable angina.
Poorly controlled hypertension.
Performance status 3, 4.
Symptomatic or progressive brain metastases.
Active infection or other serious underlying disease.
Concomitant participation in other clinical trials.
Pregnant women or nursing mothers; patients of childbearing potential without effective contraception.
Absolute medical contraindication to the use of corticosteroid premedication.
Allergy to polysorbate 80, doxorubicin, or egg lecithin.
NCI-CTC grade > 1 peripheral neuropathy.
Patients not able to comply with regular medical follow-up

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Ziekenhuis Rijnstate	Arnhem	Netherlands	6800 TA
2	Wilhelmina Ziekenhuis	Assen	Netherlands	9400 RA
3	Catharina-Ziekenhuis	Eindhoven	Netherlands	5602 ZA
4	Ikazia Ziekenhuis	Rotterdam	Netherlands	3083 AN
5	Maxima Medisch Centrum	Veldhoven	Netherlands	5500 MB
6	VieCuri MC	Venlo	Netherlands	5900 BX
7	Streekziekenhuis Koningin Beatrix	Winterswijk	Netherlands	7100 GG