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Breast CancerPhase 2NCT00036868

Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast Cancer

A Phase 2 study testing trastuzumab, CMF regimen and cyclophosphamide in people with Breast Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 13 sites in 9 countries.

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

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, methotrexate, and fluorouracil 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… Read more about this study

Who is it for?
Ages 18 to 120 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
trastuzumab, CMF regimen and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
13 sitesin 9 countries
Study dates
Feb 2002to Feb 2010
Phase
Phase 2
Are there results?
None posted in the registry

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 to 120 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic breast cancer c-erbB2 positive (3+ overexpression by the HercepTest™ method) in the primary tumor or metastatic site
  • At least 1 unidimensionally measurable target lesion
  • At least 20 mm by conventional techniques OR
  • At least 10 mm by spiral CT scan
  • Lesions that have been irradiated in the preceding 3 months cannot be used as target lesions unless they have appeared or clearly progressed since prior irradiation
  • No bone lesions as the only target lesions
  • No contralateral breast cancer that is c-erbB2-positive or c-erbB2-negative/unknown, with status determined on a metastatic site
  • No CNS metastases
  • CT scan of brain and CSF cytology are required if neurologic symptoms are present
  • Hormone receptor status:
  • Any estrogen or progesterone receptor status

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Female

Menopausal status:

  • Any status

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.25 times upper limit of normal (ULN)
  • Transaminases less than 2.5 times ULN (5 times ULN if liver metastases present)

Renal:

  • For patients age 18 to 69:
  • Creatinine no greater than ULN
  • For patients age 70 and over:
  • Creatinine clearance normal

Cardiovascular:

  • LVEF normal by MUGA or echocardiogram
  • No clinical heart failure

Pulmonary:

  • No malignancy-associated dyspnea at rest
  • No requirement for supportive oxygen therapy

Other:

  • Not pregnant or nursing
  • No other prior or concurrent malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
  • No psychological, familial, sociological, or geographical condition that would preclude compliance with study therapy and follow-up schedule

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior anti-c-erbB2 antibody, including trastuzumab (Herceptin®)
  • No other concurrent biologic therapy

Chemotherapy:

  • No more than 1 prior chemotherapy regimen for metastatic breast cancer
  • Prior combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) allowed in the adjuvant or metastatic setting only if the disease-free interval after completion of CMF was at least 12 months
  • Prior anthracyclines and/or taxanes allowed
  • At least 4 weeks since prior anthracyclines
  • No prior cumulative dose of doxorubicin more than 360 mg/m^2
  • No prior cumulative dose of epirubicin more than 720 mg/m^2
  • No prior cumulative dose of mitoxantrone more than 90 mg/m^2
  • No other concurrent chemotherapy

Endocrine therapy:

  • More than 2 weeks since prior hormonal therapy in the adjuvant or metastatic setting
  • No concurrent hormonal therapy

Radiotherapy:

  • See Disease Characteristics
  • No concurrent radiotherapy

Surgery:

  • Not specified

Other:

  • No other concurrent anticancer therapy or investigational drugs
  • No concurrent bisphosphonates started after study enrollment except for hypercalcemia

Trial locations and contacts

13 sites in 9 countries.

13 sites in 9 countries

Belgium3 sites

  • Ziekenhuis Netwerk Antwerpen Middelheim

    Antwerp, 2020

  • Institut Jules Bordet

    Brussels, 1000

  • Universitair Ziekenhuis Antwerpen

    Edegem, B-2650

Other trials in Belgium

Netherlands3 sites

  • Onze Lieve Vrouwe Gasthuis

    Amsterdam, 1091 HA

  • Leiden University Medical Center

    Leiden, 2300 CA

  • Nijmegen Cancer Center at Radboud University Medical Center

    Nijmegen, NL-6500 HB

Other trials in Netherlands

Denmark1 site

  • Herlev Hospital - University Hospital of Copenhagen

    Copenhagen, DK-2730

Other trials in Denmark

Egypt1 site

  • National Cancer Institute of Egypt

    Cairo

Other trials in Egypt

France1 site

  • Centre de Lutte Contre le Cancer Georges-Francois Leclerc

    Dijon, 21079

Other trials in France

Poland1 site

  • Medical University of Gdansk

    Gdansk, 80-211

Other trials in Poland

Serbia1 site

  • Institute of Oncology and Radiology of Serbia

    Belgrade, 11000

Other trials in Serbia

South Africa1 site

  • Medical Oncology Centre of Rosebank

    Johannesburg, 2193

Other trials in South Africa

United Kingdom1 site

  • Western Infirmary

    Glasgow, Scotland, G11 6NT

Other trials in United Kingdom

About this study

Official title: A Randomized Phase II Study Of CMF Alone And In Combination With Anti c-erbB2 Antibody (Herceptin) In Women With c-erbB2 Positive Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, methotrexate, and fluorouracil 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. Combining chemotherapy with trastuzumab may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining combination chemotherapy with trastuzumab in treating women who have metastatic breast cancer.

Read the detailed description

OBJECTIVES:

  • Compare the incidence of clinical heart failure in women with c-erbB2-positive metastatic breast cancer treated with cyclophosphamide, methotrexate, and fluorouracil in combination with trastuzumab (Herceptin®).
  • Compare the therapeutic activity of this regimen, in terms of objective response rate, in these patients.
  • Compare the duration of response and time to progression in patients treated with this regimen.
  • Compare the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive CMF comprising cyclophosphamide orally on days 1-14 or IV on days 1 and 8 and methotrexate IV and fluorouracil IV on days 1 and 8. Patients also receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day 1. Treatment repeats every 4 weeks for 8 courses. Patients then receive trastuzumab once every 3 weeks in the absence of disease progression, unacceptable toxicity, or patient refusal.

Patients are followed every 8 weeks until documentation of disease progression or initiation of a new anticancer therapy. Patients developing disease progression are followed every 12 weeks.

PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study within 2 years.

Conditions
Breast Cancer
Keywords
stage IV breast cancer, recurrent breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

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

Study groups in NCT00036868
Study groupRoleWhat they receive
CMF + HerceptinExperimentalNot described
Receives: Biological: trastuzumab; Drug: CMF regimen; Drug: cyclophosphamide; Drug: fluorouracil; Drug: methotrexate

What is being measured

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

  1. Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG

    Measured: from registration

  2. Response rate by RECIST

    Measured: from registration

Secondary outcomes (3)

  1. Duration of response by RECIST

    Measured: from registration

  2. Time to progression

    Measured: from registration

  3. Toxicity measured by CTC v2.0

    Measured: from registration

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 startFeb 2002
  3. Primary completionJun 2009
  4. Study completionFeb 2010

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00036868
Sponsor's protocol ID
EORTC-10995-16999
Other IDs
EORTC-10995, EORTC-16999, IDBBC-EORTC-10995
Status last verified
Mar 2024
First submitted
13 May 2002
Last updated
8 Mar 2024
Results posted
No

Publications

  • Neskovic-Konstantinovic Z, Nooij M, Khaled H, et al.: Safety and efficacy of combined trastuzumab and CMF therapy in women with metastatic breast cancer: EORTC protocol 10995. [Abstract] J Clin Oncol 25 (Suppl 18): A-1040, 2007.

  • Tryfonidis K, Marreaud S, Khaled H, De Valk B, Vermorken J, Welnicka-Jaskiewicz M, Aalders K, Bartlett JMS, Biganzoli L, Bogaerts J, Cameron D; EORTC- Breast Cancer Group. Cardiac safety, efficacy, and correlation of serial serum HER2-extracellular domain shed antigen measurement with the outcome of the combined trastuzumab plus CMF in women with HER2-positive metastatic breast cancer: results from the EORTC 10995 phase II study. Breast Cancer Res Treat. 2017 Jun;163(3):507-515. doi: 10.1007/s10549-017-4203-y. Epub 2017 Mar 21.

    PubMed 28324265

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing trastuzumab, CMF regimen and cyclophosphamide in people with Breast Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 13 sites in 9 countries.

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

Who may be eligible to take part?

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 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Belgium, Netherlands, Denmark, Egypt, France and 4 more countries. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG (time frame: from registration). 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 NCT00036868, which also lists 2 linked publications.

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 8 Mar 2024.

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