AzTrials
AzTrials

Breast CancerPhase 315-95NCT00002784

High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Combination Chemotherapy in Treating Women With High-Risk Breast Cancer

A Phase 3 study testing filgrastim, CMF regimen and cyclophosphamide in people with Breast Cancer, run by ETOP IBCSG Partners Foundation at 11 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Read more about this study

Who is it for?
Ages 16 to 65 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
filgrastim, CMF regimen and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
344 participants
Where
11 sitesin 2 countries
Study dates
Jun 1996to Dec 2011
Phase
Phase 3
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 16 to 65 years
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

DISEASE CHARACTERISTICS: Histologically proven breast carcinoma in one of the following categories: 10 or more involved axillary nodes 5 or more involved axillary nodes and either: Primary tumor estrogen receptor (ER)-negative (less than 10 femtomoles per milligram of cytosol protein) T3 tumor (regardless of ER status) Total mastectomy or breast-conserving procedure (lumpectomy or quadrantectomy) required within 6 weeks prior to randomization Tumor confined to breast and axillary nodes (T1a-c, T2, or T3, N1-2, M0 by the UICC staging system) The following conditions exclude entry: Satellite skin nodules distant from the primary tumor Supraclavicular node involvement Inoperable, matted axillary nodes Fixation of primary tumor to chest wall (excluding pectoralis major) Bilateral breast cancer (any mass in opposite breast unless biopsy-proven benign) Hot spots on bone scintigram (unless confirmed to be benign) Skeletal pain of unknown cause Hormone receptor status: ER status determination preferred, but not required

PATIENT CHARACTERISTICS: Age: 16-65 Sex: Women only Menopausal status: Any status Performance status: ECOG 0-2 Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin no greater than 1.1 mg/dL (20 micromoles/L) AST no greater than twice normal Renal: Creatinine no greater than 1.3 mg/dL (120 micromoles/L) Cardiovascular: Left ventricular ejection fraction greater than 50% by MUGA Other: No second malignancy except: Basal cell carcinoma Adequately treated carcinoma in situ of the cervix No significant nonmalignant disease that would preclude participation No psychiatric or addictive disorder that would compromise informed consent or participation No pregnant or nursing women Adequate contraception strongly advised for fertile women

PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer other than surgery (see Disease Characteristics)

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

Switzerland6 sites

  • Swiss Institute for Applied Cancer Research

    Bern, CH-3008

  • Inselspital, Bern

    Bern, CH-3010

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

  • Istituto Oncologico della Svizzera Italiana

    Lugano, CH-6900

  • Kantonsspital - Saint Gallen

    Sankt Gallen, CH-9007

  • Universitaetsspital

    Zurich, CH-8091

Other trials in Switzerland

Australia5 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Queen Elizabeth Hospital

    Adelaide, South Australia, 5011

  • Newcastle Mater Misericordiae Hospital

    Newcastle, New South Wales, NSW 2310

  • Royal Melbourne Hospital

    Parkville, Victoria, 3050

  • Royal Prince Alfred Hospital, Sydney

    Sydney, New South Wales, 2050

Other trials in Australia

About this study

Official title: Randomized Trial of High-dose Epirubicin and Cyclophosphamide x 3 Supported by Peripheral Blood Progenitor Cells Versus Anthracycline and Cyclophosphamide x 4 Followed by Cyclophosphamide, Methotrexate, and 5-fluorouracil x 3 as Adjuvant Treatment for High Risk Operable Stage ii and Stage Iii Breast Cancer in Premenopausal and Young Postmenopausal (Less Than or Equal to 65 Yrs) Patients.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known if high-dose combination chemotherapy plus peripheral stem cell transplantation is more effective than standard combination chemotherapy for breast cancer.

PURPOSE: Randomized phase III trial to compare high-dose combination chemotherapy plus peripheral stem cell transplantation with standard combination chemotherapy in treating women with stage II or stage III breast cancer.

Read the detailed description

OBJECTIVES: I. Compare the survival, disease-free survival, and systemic disease-free survival of women with high-risk, operable stage II/III breast cancer treated with three courses of dose-intensive epirubicin/cyclophosphamide (EC) supported by granulocyte colony-stimulating factor (G-CSF) and G-CSF-mobilized peripheral blood stem cells vs. standard EC followed by cyclophosphamide/methotrexate/fluorouracil. II. Compare the toxicity, duration of quality-adjusted time without symptoms and toxicity, and quality of life associated with these two treatments. III. Evaluate the cost effectiveness of these two treatments.

OUTLINE: This is a randomized study. Patients are stratified by estrogen receptor status and menopausal status. Within 6 weeks of surgery, patients in the first group receive epirubicin (preferred) or doxorubicin plus cyclophosphamide every 3 weeks for 4 courses followed by conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) every 4 weeks for 3 courses. Patients in the second group undergo stem cell mobilization and harvest with granulocyte colony-stimulating factor (G-CSF) followed within 10 weeks of surgery by high-dose chemotherapy with epirubicin and cyclophosphamide followed by peripheral blood stem cell rescue and G-CSF. All patients receive adjuvant tamoxifen, and patients who underwent lumpectomy prior to entry are required to receive adjuvant radiotherapy (radiotherapy is optional for patients who underwent mastectomy prior to entry). Patients are followed every 3 months for 2 years, then q 6 months for 3 years, then yearly.

PROJECTED ACCRUAL: 210 patients will be accrued over 4 years to provide 195 evaluable patients.

Conditions
Breast Cancer
Being tested
filgrastim, CMF regimen, cyclophosphamide, doxorubicin hydrochloride, epirubicin hydrochloride
Keywords
stage II breast cancer, stage IIIA 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.

  • filgrastimBiological

    Filgrastim 10 mg/kg/d sc for 6 days after randomization.

  • CMF regimenDrug

    Cyclophosphamide 100 mg/m2 orally days 1 - 14, methotrexate 40 mg/m2 iv days 1 and 8, 5-fluorouracil 600 mg/m2 iv days 1 and 8. Repeat every 28 days.

  • cyclophosphamideDrug

    For high-dose EC arm: cyclophosphamide 4 gm/m2 iv as 4 divided doses. For standard chemotherapy arm: cyclophosphamide 600 mg/m2 iv day 1 of 21-day EC cycles, and cyclophosphamide 100 mg/m2 orally on days 1-14 of 28-day CMF cycles.

  • doxorubicin hydrochlorideDrug

    Doxorubicin 60 mg/m2 iv on day 1 of 21-day cycles of AC.

  • epirubicin hydrochlorideDrug

    Epirubicin 90 mg/m2 iv on day 1 of 21-day cycles of EC.

  • fluorouracilDrug

    5-fluorouracil 600 mg/m2 iv days 1 and 8 of 28-day cycles of CMF.

  • mesnaDrug

    MESNA (7.2 gm/m2) on days 2 and 3 of 21-day cycles of dose-intensive EC.

  • methotrexateDrug

    Methotrexate 40 mg/m2 iv on days 1 and 8 of 28-day cycles of CMF.

  • tamoxifen citrateDrug

    Tamoxifen 20mg daily for 5 years or until relapse.

  • peripheral blood stem cell transplantationProcedure or surgery

    Peripheral blood progenitor cells (PBPC) infusion on day 5 of each 21-day cycle of dose-intensive EC.

  • low-LET electron therapyRadiation

    Radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.

  • low-LET photon therapyRadiation

    radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.

Study groups in NCT00002784
Study groupRoleWhat they receive
Standard chemotherapyActive comparatorEC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization.
Receives: Drug: CMF regimen; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: epirubicin hydrochloride; Drug: fluorouracil; Drug: methotrexate; Drug: tamoxifen citrate; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy
Dose-intensive ECExperimentalHigh-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization.
Receives: Biological: filgrastim; Drug: cyclophosphamide; Drug: mesna; Drug: tamoxifen citrate; Procedure: peripheral blood stem cell transplantation; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy

What is being measured

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

  1. Disease-free survival.

    Time from randomization to recurrence (including recurrence isolated to the breast), metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first.

    Measured: 16 years after randomization.

Secondary outcomes (3)

  1. Overall survival.

    Time from randomization to death from any cause.

    Measured: 16 years after randomization.

  2. Toxicity.

    Morbidity information was recorded using standard toxicity criteria.

    Measured: 5 years after randomization.

  3. Quality of life.

    Quality of life was assessed using standard International Breast Cancer Study Group instruments.

    Measured: 16 years after randomization.

Timeline

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

  1. First posted29 Jul 2004 (estimated)
  2. Study startJun 1996
  3. Primary completionAug 2011
  4. Study completionDec 2011

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
344 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00002784
Sponsor's protocol ID
CDR0000064834
Other IDs
IBCSG-15-95, EU-96021
Acronym
15-95
Status last verified
Jul 2012
First submitted
1 Nov 1999
Last updated
4 Apr 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Pestalozzi BC, Zahrieh D, Mallon E, Gusterson BA, Price KN, Gelber RD, Holmberg SB, Lindtner J, Snyder R, Thurlimann B, Murray E, Viale G, Castiglione-Gertsch M, Coates AS, Goldhirsch A; International Breast Cancer Study Group. Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol. 2008 Jun 20;26(18):3006-14. doi: 10.1200/JCO.2007.14.9336. Epub 2008 May 5.

    PubMed 18458044

  • Keshaviah A, Dellapasqua S, Rotmensz N, Lindtner J, Crivellari D, Collins J, Colleoni M, Thurlimann B, Mendiola C, Aebi S, Price KN, Pagani O, Simoncini E, Castiglione Gertsch M, Gelber RD, Coates AS, Goldhirsch A. CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann Oncol. 2007 Apr;18(4):701-8. doi: 10.1093/annonc/mdl492. Epub 2007 Jan 20.

    PubMed 17237474

  • Colleoni M, Sun Z, Martinelli G, Basser RL, Coates AS, Gelber RD, Green MD, Peccatori F, Cinieri S, Aebi S, Viale G, Price KN, Goldhirsch A; International Breast Cancer Study Group. The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up. Ann Oncol. 2009 Aug;20(8):1344-51. doi: 10.1093/annonc/mdp024. Epub 2009 May 25.

    PubMed 19468030

  • International Breast Cancer Study Group; Basser RL, O'Neill A, Martinelli G, Green MD, Peccatori F, Cinieri S, Coates AS, Gelber RD, Aebi S, Castiglione-Gertsch M, Viale G, Price KN, Goldhirsch A. Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95. J Clin Oncol. 2006 Jan 20;24(3):370-8. doi: 10.1200/JCO.2005.03.5196.

    PubMed 16421418

  • Basser RL, Abraham R, To LB, Fox RM, Green MD. Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer. Ann Oncol. 1999 Jan;10(1):53-8. doi: 10.1023/a:1008390203340.

    PubMed 10076722

  • Basser RL, To LB, Collins JP, Begley CG, Keefe D, Cebon J, Bashford J, Durrant S, Szer J, Kotasek D, Juttner CA, Russell I, Maher DW, Olver I, Sheridan WP, Fox RM, Green MD. Multicycle high-dose chemotherapy and filgrastim-mobilized peripheral-blood progenitor cells in women with high-risk stage II or III breast cancer: five-year follow-up. J Clin Oncol. 1999 Jan;17(1):82-92. doi: 10.1200/JCO.1999.17.1.82.

    PubMed 10458221

  • Basser RL, To LB, Begley CG, Juttner CA, Maher DW, Szer J, Cebon J, Collins JP, Russell I, Olver I, et al. Adjuvant treatment of high-risk breast cancer using multicycle high-dose chemotherapy and filgrastim-mobilized peripheral blood progenitor cells. Clin Cancer Res. 1995 Jul;1(7):715-21.

    PubMed 9816037

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing filgrastim, CMF regimen and cyclophosphamide in people with Breast Cancer, run by ETOP IBCSG Partners Foundation at 11 sites in 2 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 4 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Switzerland, Australia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Disease-free survival. (time frame: 16 years after randomization.). 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 NCT00002784, which also lists 7 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 4 Apr 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
15-95 Clinical Trial NCT00002784 | AzTrials