A Study to Determine the Activity of Caelyx With Trastuzumab and Docetaxel in the Treatment of Metastatic Breast Cancer (Study P03679)(COMPLETED)

This study has been completed.
Sponsor:
Collaborator:
MDS Pharma Services
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00687440
First received: May 27, 2008
Last updated: October 10, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to evaluate, in a first stage, the safety (incidence of cardiac toxicity) of Caelyx in combination with Trastuzumab and Docetaxel; and in a second stage, the tumor response rate of this regimen. This study will be conducted in approximately 30 centers. A total of approximately 70 to 95 subjects will be enrolled.


Condition Intervention Phase
Breast Neoplasm
Drug: Pegylated Liposomal Doxorubicin
Drug: Docetaxel
Drug: Trastuzumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pegylated Liposomal Doxorubicin (Caelyx) in Combination With Herceptin and Taxotere as First-line Chemotherapy in Metastatic Breast Cancer Patients: A 2 Stage Phase II, Open Label, Multicenter Study.

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria [ Time Frame: Week 09, Week 18, at the end of each patient's treatment, and at 3, 6, 9, and 12 months after end of treatment. ] [ Designated as safety issue: No ]
    Those who achieved either complete (disappearance of all target lesions) or partial (at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD) response.


Enrollment: 27
Study Start Date: May 2005
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Caelyx, Docetaxel, Trastuzumab

Stage 1: subjects will receive Caelyx one day every 3 weeks in combination with docetaxel one day every 3 weeks and trastuzumab once weekly during 6 cycles. At the end of this stage, based on the number of cardiac events, subjects will proceed to a second stage or restart with a lower dose of Caelyx.

Stage 2: subjects will be treated with the recommended dose of Caelyx (defined in the first stage) in combination with docetaxel and trastuzumab.

Drug: Pegylated Liposomal Doxorubicin

Stage 1: 25 subjects will be treated with Caelyx IV 30 mg/m^2 on day 1, every 3 weeks

Stage 2: 45 new patients will be treated at the recommended dose level (defined in the first step) on day 1, every 3 weeks.

Other Name: Caelyx
Drug: Docetaxel
Stage 1 and Stage 2: Docetaxel 60 mg/m2 IV as 1-hour infusion, on day 1, every 3 weeks.
Other Name: Taxotere
Drug: Trastuzumab
Stage 1 and Stage 2: 4 mg/kg IV 90-minute infusion loading dose. Then 2 mg/kg IV weekly during 6 cycles (18 weeks).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must fulfill all the following criteria:

  • Females aged 18 to 70 years-old.
  • Willingness to participate in the study and comply with its procedures.
  • Documented diagnosis of metastatic breast carcinoma (stage IV) Human Epidermal Growth Factor Receptor 2 (HER2) overexpressing (Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization(FISH) +).
  • No prior chemotherapy for metastatic breast cancer.
  • Adjuvant or neo-adjuvant chemotherapy is allowed according to the following rules:

    • patients treated with anthracyclines if all the following conditions are met:

      • Doxorubicin total dose <= 300 mg/m^2
      • Epirubicin total dose <= 480 mg/m^2
      • Chemotherapy-free interval of > 12 months
    • no taxane-based adjuvant or neo-adjuvant chemotherapy is allowed;
    • patients treated with non-anthracycline/taxane adjuvant or neo-adjuvant chemotherapy regimens are freely eligible (i.e. cyclophosphamide/methotrexate/fluorouracil (CMF) or similar regimens).
  • At least one measurable lesion according to RECIST criteria.
  • Complete hematologic and biologic baseline evaluation within 2 weeks prior to start of treatment.
  • Complete Tumor baseline evaluation including a total body computed tomography (CT) scan within 4 weeks prior to start of treatment.
  • Left ventricular ejection fraction (LVEF) >= 50% as determined by echocardiogram or Multi Gated Acquisition (MUGA) scan.
  • World Health Organization (WHO) performance status 0,1.
  • Life expectancy > 3 months.
  • Laboratory requirements :

    • Hematology :

      • Neutrophils > 1.5 x 10^9/L
      • Platelets > 100 x 10^9/L
      • Hemoglobin > 10 g/dL
    • Hepatic function:

      • Total bilirubin <= 1.25 x the upper-normal limits (UNL);
      • ASAT (Aspartate Aminotransferase or SGOT), ALAT (Alanine aminotransferase or SGPT) <= 2.5 x the upper-normal limits;
    • For patients with liver metastases:

      • Total bilirubin < 1.5 x the UNL (Upper limit of normal) ;
      • ASAT and/or ALAT < 3 x the UNL;
    • Renal function :

      • Serum Creatinine < 1.5 x the UNL.
  • Women of child bearing potential must have a negative serum pregnancy test and be using adequate contraception.
  • Patients must be accessible for treatment and follow-up.

Exclusion Criteria:

Patients will not be enrolled if any of the following criteria apply:

  • Prior chemotherapy for metastatic disease.
  • History of prior malignancy in the last 10 years (other than non melanoma skin cancer or excised cervical carcinoma in situ).
  • Radiation to disease areas within 3 weeks of study initiation.
  • Symptomatic peripheral neuropathy > grade 2 according to the National Cancer Institute (NCI) Common Toxicity Criteria.
  • Other serious illness or medical condition.
  • LVEF < 50% as determined by echocardiogram or MUGA scan.
  • Congestive hearth failure or angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled high risk hypertension or arrhythmia.
  • History of significant neurologic or psychiatric disorders including dementia or seizures.
  • Active infection.
  • Active peptic ulcer, unstable diabetes mellitus or other contraindications for the use of dexamethasone.
  • Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
  • Concurrent treatment with corticosteroids used for reasons other than for premedication. However patients receiving chronic treatment with corticosteroids (> 6 months) at low dose (< 20 mg of methylprednisolone or equivalent dose of other corticosteroids) for whichever reason are eligible.
  • Taxane-based adjuvant or neo-adjuvant chemotherapy < 12 months.
  • Other concurrent chemotherapy, immunotherapy, radiotherapy or any other investigational medication, for the treatment of the tumor.
  • Pregnant or breast-feeding women.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00687440     History of Changes
Other Study ID Numbers: P03679, Eudract No. 2004-003989-15
Study First Received: May 27, 2008
Results First Received: January 21, 2010
Last Updated: October 10, 2013
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Doxorubicin
Docetaxel
Trastuzumab
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014