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Recurrent Breast CancerPhase 2NCT00004888

Combination Chemotherapy With or Without Trastuzumab in Treating Women With Metastatic Breast Cancer

A Phase 2 study testing pegylated liposomal doxorubicin hydrochloride, docetaxel and trastuzumab in people with Recurrent Breast Cancer and Stage IV Breast Cancer, run by National Cancer Institute (NCI) 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

Phase II trial to study the effectiveness of combination chemotherapy with or without trastuzumab in treating women who have metastatic breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
pegylated liposomal doxorubicin hydrochloride, docetaxel and trastuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
1 siteUnited States
Study dates
Jan 2001to May 2009
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed adenocarcinoma of the breast with manifestations of metastatic progression
  • HER2 expression status in primary breast tissue and/or site(s) of metastasis must be determined by the ECOG Pathology Coordinating Office; (these are the results that will be used at time of registration); NOTE: for this protocol, HER2/neu non-overexpressed status will be defined as 0 and 1+ scores using the DAKO HercepTest; HER2 overexpressed status will be defined as 2+ score (if confirmed amplified by FISH) or 3+ score using the DAKO HercepTest
  • Cytologically positive pleural or peritoneal effusions are considered evaluable disease provided local intra-cavitary treatment is not introduced at the onset of therapy; to be considered as evaluable disease, pleural effusions may not have been previously drained or sclerosed
  • Blastic or mixed blastic/lytic osseous metastases only are evaluable disease provided they are accompanied by an analgesic requirement or a decrease in performance status, and will not require radiation treatment within two cycles from the start of protocol; pure osteolytic disease is evaluable; bone disease must be x-ray proven for the site to be evaluable; patients whose only evidence of metastatic disease is an abnormal bone scan without confirmatory x-rays are not eligible for this study
  • No prior chemotherapy for advanced disease; prior adjuvant chemotherapy (including taxanes) allowed, if completed > 6 months before the diagnosis of metastatic disease; no prior adjuvant anthracycline, nor any prior exposure to other anthracycline- (e.g., epirubicin, any liposomal doxorubicin formulation), nor any anthracenedione- (e.g., mitoxantrone) containing regimen allowed; no prior therapy with Herceptin allowed; NOTE: chemotherapy after ipsilateral breast recurrence following breast conservation surgery would not be considered chemotherapy for advanced disease; however, in post-mastectomy patients chemotherapy for local/regional recurrence is considered treatment for advanced disease
  • No prior radiotherapy other than to the conserved breast, to the post-mastectomy chest wall, or to a limited field involving < 25% of marrow-containing bone; NOTE: previous post-mastectomy radiation therapy involving chest wall ± internal mammary lymph node chain (IMN) is allowed; however, patients who received photon IMN treatment are ineligible; NOTE: radiotherapy must be completed >= 2 weeks prior to registration; it may not be given concurrently with Doxil, Taxotere, or Herceptin
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  • Prior hormonal therapy in either a metastatic or adjuvant setting is allowed, but patients must have been off such therapy for >= 2 weeks prior to registration
  • Disease-free of prior non-breast invasive malignancies for >= 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • ECOG performance status of 0, 1, or 2
  • At least two weeks after any major surgery (including mastectomy) and recovered from all toxicity
  • Creatinine =< 1.5 mg/dl
  • Granulocytes >= 1,500/mm³
  • Platelets >= 100,000/mm³
  • SGOT(AST) =< 2.5 x the upper limit of normal
  • Bilirubin within normal limits for institution
  • No history of deep venous thrombosis, pulmonary thromboembolism, or other thromboembolic condition
  • Women must not be pregnant or breastfeeding; the effect of Herceptin to the fetus is unknown; Doxil is known to be harmful to the fetus
  • Women of childbearing potential must be advised to use an accepted and effective method of contraception
  • No patients with untreated brain metastasis or brain metastasis undergoing radiation or for whom brain metastasis represent the sole site of disease; patients with previously treated brain metastasis who have responded to brain radiotherapy and/or surgery and continue in response are eligible, provided the brain is not the only site of disease
  • The left ventricular ejection fraction must be at or above the lower institutional limits of normal (as assessed by MUGA scan or echocardiogram obtained within six weeks prior to registration); patient will not be eligible if baseline LVEF assessment not performed
  • No prior history of myocardial infarction, congestive heart failure, or arrhythmia requiring medication; no history of hypertension or systolic or diastolic dysfunction; no EKG evidence of ventricular hypertrophy, conduction abnormality, or serious arrhythmia; patient will not be eligible if baseline EKG assessment not performed within 4 weeks

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Safety and Efficacy Study of Doxil and Taxotere ± Herceptin in Advanced Breast Cancer

Phase II trial to study the effectiveness of combination chemotherapy with or without trastuzumab in treating women who have metastatic breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and feasibility of the combination of liposomal doxorubicin (Doxil) and Taxotere (Taxotere) ± trastuzumab (Herceptin), particularly with respect to cardiotoxicity.

II. To evaluate the overall objective response rate, response duration, time to treatment failure, and median survival of patients with metastatic breast cancer treated with Doxil and Taxotere ± Herceptin.

III. To determine the overall toxicity of Doxil and Taxotere ± Herceptin in patients with advanced breast cancer.

IV. To determine whether there is an association between trough plasma levels of cTnT (cardiac troponin T) and NT-proBNP (brain natriuretic peptide) and any cardiac event (CHF or LVEF decrease).

  1. To determine tissue and plasma levels of HER2 using several assays and explore potential correlation with protocol treatment toxicity and/or response.

OUTLINE: Patients are assigned to one of two treatment arms according to HER2 overexpression status.

Arm I (HER2 nonoverexpressed): Patients receive doxorubicin hydrochloride liposome IV over 30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

Arm II (HER2 overexpressed): Patients receive trastuzumab IV over 90 minutes on day 1, with subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3 weeks for 8 courses.

Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 89 patients were accrued for this study.

Being tested
pegylated liposomal doxorubicin hydrochloride, docetaxel, trastuzumab, laboratory biomarker analysis
Medical subject headings
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

  • docetaxelDrug

    Also called RP 56976, Taxotere, TXT

    Given IV

  • trastuzumabBiological

    Also called anti-c-erB-2, Herceptin, MOAB HER2

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00004888
Study groupRoleWhat they receive
Arm I (combination chemotherapy)ExperimentalPatients receive doxorubicin hydrochloride liposome IV over 30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: docetaxel; Other: laboratory biomarker analysis
Arm II (combination chemotherapy, trastuzumab)ExperimentalPatients receive trastuzumab IV over 90 minutes on day 1, with subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3 weeks for 8 courses. Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: pegylated liposomal doxorubicin hydrochloride; Drug: docetaxel; Biological: trastuzumab; Other: laboratory biomarker analysis

What is being measured

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

  1. Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event

    This table summarizes the cardiotoxicity events of different grades. Grade 1 is a decline of left ventricular ejection fraction(LVEF) >=10% but <20% of baseline value. Grade 2 is LVEF below LLN (50%) or decline of LVEF >=20% of baseline value. Grade 3 is congestive heart failure responsive to treatment. Please note that only a subset of patients reported cardiotoxic events so the totals will not add up to the total number of participants.

    Measured: Baseline, after cycle 4 (~84 days), after cycle 8 (~168 days), and 30 or more days after last cycle of induction therapy

  2. Summary of Left Ventricular Ejection Fraction Values

    This table summarizes the LVEF information at baseline, post Cycle 4, post Cycle 8, and 30 or more days after Cycle 8 on all treated patients and on the eligible subset. LVEF drops reported are absolute (not relative) drops.

    Measured: Baseline, after cycle 4, after cycle 8, and 30 or more days after last cycle of induction therapy.

Secondary outcomes (4)

  1. Best Overall Response Using Eastern Cooperative Group Solid Tumor Response Criteria.

    Please note that overall response includes CR and PR. CR is defined as complete disappearance of all clinically detectable malignant disease for at least 4 weeks. PR is greater than or equal to 50% decrease in tumor size for at least 4 weeks without increase in size of any area of known malignant disease of greater than 25%, or appearance of new areas of malignant disease. No change is defined as no significant change in measurable or evaluable disease for at least 4 weeks. Progression is defined as a significant increase in size of lesions present at the start of therapy or after a response.

    Measured: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of Nov 21, 2007 is used for this report. Please note that best overall response is reported in the table.

  2. Overall Survival

    Measured: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.

  3. Progression-Free Survival

    Progression-Free Survival was defined as time from study entry to progression or to death without documentation of progression. A progression is defined as a significant increase in size of lesions present at the start of therapy or after a response.

    Measured: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.

  4. Duration of Response

    Defined as time from onset of PR or CR, whichever occurred first, until objective evidence of progression.

    Measured: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startJan 2001
  3. Primary completionApr 2008
  4. Study completionMay 2009

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004888
Sponsor's protocol ID
NCI-2012-02949
Other IDs
NCI-2012-02949, E3198, E3198, U10CA021115
Status last verified
Dec 2012
First submitted
7 Mar 2000
Last updated
23 May 2014

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pegylated liposomal doxorubicin hydrochloride, docetaxel and trastuzumab in people with Recurrent Breast Cancer and Stage IV Breast Cancer, run by National Cancer Institute (NCI) 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 21 inclusion and 0 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 23 May 2014. 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 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 Nov 2011). 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?

Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event (time frame: Baseline, after cycle 4 (~84 days), after cycle 8 (~168 days), and 30 or more days after last cycle of induction therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004888.

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 May 2014.

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