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HER2-positive Breast CancerPhase 1/2NCT00331552

Doxorubicin Hydrochloride Liposome, Cyclophosphamide, and Trastuzumab in Treating Patients With Stage IV Breast Cancer

A Phase 1/2 study testing pegylated liposomal doxorubicin hydrochloride, cyclophosphamide and trastuzumab in people with HER2-positive Breast Cancer and Male Breast Cancer, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pegylated liposomal doxorubicin hydrochloride, cyclophosphamide and trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Feb 2006to Feb 2012
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must satisfy either a or b: a) Measurable disease by RECIST criteria; x-rays, scans or physical examinations used for tumor assessment must have been completed within 30 days prior to registration; any non-measurable disease must be assessed within 42 days prior to registration; b) Non-measurable disease only, but MUC-1 antigen level (either CA 27-29 or CEA) is > 2X ULN AND MUC-1 antigen has been documented to have increased by 1.5X prior to registration; x-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration
  • ECOG performance status of =< 2
  • ANC >= 1,500 cells/mm^3
  • Platelet count >= 100,000 cells/mm^3
  • Hemoglobin >= 9.0g/dL
  • Creatinine =< 2.5 mg/dL
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  • In the absence of liver metastases, AST / ALT, alkaline phosphatase and total bilirubin must not exceed 2 x upper limit of normal (i.e., must be =< 2 x upper limit of normal)
  • In the presence of liver metastases, AST / ALT, alkaline phosphatase and total bilirubin must not exceed 3 x upper limit of normal (i.e., must be =< 3 x upper limit of normal)
  • Have a MUGA scan or 2-d echocardiogram indicating an ejection fraction of >= 50% within 42 days prior to first dose of study drug (the method used at baseline must be used for later monitoring)
  • Use an adequate contraceptive method (e.g., abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment if of reproductive potential
  • Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures

Who cannot join

  • Pregnant or lactating women
  • History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the components of Doxil
  • Patients who are HER2-neu positive with cardiac disease that would preclude the use of Doxil or Herceptin are not eligible, including active cardiac disease (i.e., angina pectoris that requires the use of antianginal medication, cardiac arrhythmia requiring medication, severe conduction abnormality, clinically significant valvular disease, cardiomegaly on chest x-ray, ventricular hypertrophy on EKG, uncontrolled hypertension [diastolic greater than 100 mm/Hg or systolic > 200 mm/hg], current use of digitalis or beta blockers for CHF, clinically significant pericardial effusion) and history of cardiac disease (i.e., myocardial infarction documented as a clinical diagnosis or by EKG or any other test, documented congestive heart failure, documented cardiomyopathy, documented arrhythmia or cardiac valvular disease that requires medication or is medically significant)
  • Has anthracycline resistant disease defined as a) If anthracycline was given for non-metastatic disease: The cumulative dose of anthracycline exceeds 360 mg/m^ 2 for doxorubicin or 540 mg/m^2 for epirubicin AND the disease-free interval from discontinuation of anthracycline to diagnosis of metastatic disease is < 12 months; b) If anthracycline was given for metastatic disease: The cumulative dose of anthracycline exceeds 360 mg/m^2 for doxorubicin or 540 mg/m^2 for epirubicin AND the patient's disease progressed on anthracycline given as palliative therapy
  • Except for the following no other malignancy is allowed: synchronous ipsilateral breast cancer of the same subtype (ER/PR, HER-2/neu), adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other stage I or II cancer from which the patient has been disease free for at least 5 years
  • Any life-threatening illness other than the malignancy for which they are being treated
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  • Mental illness
  • Have a life expectancy of less than 4 months
  • Unwillingness to participate or inability to comply with the protocol for the duration of the study

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Phase I - II Study of Doxil® In Combination With Daily Oral Cyclophosphamide and Herceptin for Patients With HER-2/Neu Positive Disease In Patients With Metastatic Breast Cancer

Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) together with trastuzumab may be a better way to block tumor growth.

Read the detailed description

PRIMARY OBJECTIVES: I. To determine the optimal tolerated dose of Doxil when given in combination with daily oral cyclophosphamide in patients with stage IV breast cancer. (Phase I) II. To determine the efficacy (overall clinical response rate) of the optimal tolerated dose of Doxil when given in combination with daily oral cyclophosphamide and herceptin (for HER2 neu positive patients) in patients with stage IV breast cancer. (Phase II) SECONDARY OBJECTIVES: I. To assess the treatment related toxicity associated with each dose level of this regimen and assess efficacy (overall clinical response rate). (Phase I) II. To assess the safety (treatment related toxicity) of the optimal tolerated dose of Doxil when given in combination with daily oral cyclophosphamide and herceptin (for HER2 neu positive patients) in patients with stage IV breast cancer. (Phase II) III. To assess time to progression and overall survival following treatment with Doxil and daily oral cyclophosphamide and herceptin (for HER2 neu positive patients). (Phase II) IV. To compare the response rate in patients who are heavily pretreated to the response rate in patients who are less heavily pretreated. OUTLINE: This is a phase I, dose-escalation study of pegylated doxorubicin HCl liposome followed by a phase II feasibility study. Patients receive oral cyclophosphamide once daily on days 1-28 and pegylated doxorubicin HCl liposome IV over 90 minutes on day 1. Treatment repeats every 4-6 weeks in the absence of disease progression or unacceptable toxicity. Some patients with HER2/neu 3+ disease may also receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks at the discretion of the treating physician. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Being tested
pegylated liposomal doxorubicin hydrochloride, cyclophosphamide, trastuzumab
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pegylated liposomal doxorubicin hydrochlorideDrug

    Also called CAELYX, Dox-SL, DOXIL, doxorubicin hydrochloride liposome

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given orally

  • trastuzumabBiological

    Also called anti-c-erB-2, Herceptin, MOAB HER2, monoclonal antibody c-erb-2

    Given IV

Study groups in NCT00331552
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral cyclophosphamide once daily on days 1-28 and pegylated doxorubicin HCl liposome IV over 90 minutes on day 1. Treatment repeats every 4-6 weeks in the absence of disease progression or unacceptable toxicity. Some patients with HER2/neu 3+ disease may also receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks at the discretion of the treating physician.
Receives: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose and Optimal Tolerated Dose of Pegylated Liposomal Doxorubicin Hydrochloride (Doxil) When Given in Combination With Cyclophosphamide (Phase I)

    The dose level in which 2 or more patients develop treatment-related toxicity of grade 3 or higher OR require a dose adjustment following the first course of treatment

    Measured: Up to 24 weeks

  2. Efficacy as Assessed by the Overall Clinical Benefit Rate

    Count of participants with a clinical benefit (i.e., complete response, partial response, and stable disease).

    Measured: 18 months

  3. Safety as Assessed by Grade 1, 2, 3, 4, Fatal Toxicity, Need for Dose Reduction, Treatment Interruption, or Treatment Discontinuation

    Count of participants with grade 1, 2, 3, 4, fatal toxicity, need for dose reduction, treatment interruption, or treatment discontinuation

    Measured: Periodically during study treatment, up to 24 weeks

Secondary outcomes (5)
  1. Treatment-related Toxicity (Phase I)

    Count of phase I participants with treatment related toxicity.

    Measured: Up to 24 weeks

  2. Time to Progression (Phase II)

    Median time to progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions or new effusions.

    Measured: Up to 2 years

  3. Progression-free Survival (Phase II)

    Kaplan-Meier estimate assessed at 18 months

    Measured: 18 months

  4. Overall Survival (Phase II)

    Kaplan-Meier estimate assessed at 18 months

    Measured: 18 months

  5. Comparison of Clinical Benefit Rate in 2 Subgroups--heavily Pre-treated (1 or More Regimens for Advanced Disease) vs Less Heavily Pre-treated (no Regimens for Advanced Disease) (Phase II)

    Count of participants with a clinical benefit (i.e., complete response, partial response, and stable disease).

    Measured: Up to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2006 (estimated)
  2. Study startFeb 2006
  3. Primary completionFeb 2011
  4. Study completionFeb 2012

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00331552
Sponsor's protocol ID
6139
Other IDs
NCI-2010-00798
Status last verified
Jun 2017
First submitted
30 May 2006
Last updated
26 Jul 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing pegylated liposomal doxorubicin hydrochloride, cyclophosphamide and trastuzumab in people with HER2-positive Breast Cancer and Male Breast Cancer, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. 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 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 26 Jul 2017). 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?

Maximum Tolerated Dose and Optimal Tolerated Dose of Pegylated Liposomal Doxorubicin Hydrochloride (Doxil) When Given in Combination With Cyclophosphamide (Phase I) (time frame: Up to 24 weeks). The study lists 3 primary outcomes in all. 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 26 Jul 2017.

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