Combination Chemotherapy and Trastuzumab in Treating Women With Stage I, Stage II, or Stage III HER2-Positive Breast Cancer

NCT00629278 | Unknown Phase 3

• 4 other identifiers: AOUMODENA-SHORT-HERCDR0000584446EUDRACT-2007-004326-25EU-20825
• Study Type: interventional
• Target: 2,500
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: Drugs used in chemotherapy 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. It is not yet known which regimen of combination chemotherapy given together with trastuzumab is most effective in treating breast cancer. PURPOSE: This randomized phase III trial is comparing two different regimens of combination chemotherapy given together with trastuzumab to see how well they work in treating women with HER2-positive stage I, stage II, or stage III breast cancer.

Conditions

Breast Cancer

Keywords

stage IA breast cancer; stage IB breast cancer; stage II breast cancer; stage IIIA breast cancer; HER2-positive breast cancer

Outcome Measures

Primary Outcomes (2)

• Disease-free survival

• Overall survival

Secondary Outcomes (2)

• Failure rate at 2 years due to relapse, death, or toxicity

• Incidence of cardiac events as assessed by NCI CTCAE V3.0

Interventions

trastuzumab BIOLOGICAL

aromatase inhibition therapy DRUG

cyclophosphamide DRUG

docetaxel DRUG

doxorubicin hydrochloride DRUG

epirubicin hydrochloride DRUG

fluorouracil DRUG

paclitaxel DRUG

releasing hormone agonist therapy DRUG

tamoxifen citrate DRUG

adjuvant therapy PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of infiltrating primary breast cancer * Stage I-IIIA disease * Resected tumor with free margins (i.e., no neoplastic cells on the resected margin) * Must have node-negative sentinel node or complete axillary clearance * Axillary clearance required for micrometastasis (between 0.2 and 2 mm) in the sentinel node but not for isolated tumor cells * Treatment is scheduled to begin within 10 weeks from the date of surgery * Date of the last surgery will be taken into account for patients undergoing re-excision of positive margins or axillary lymph node dissection after positive sentinel node biopsy * Node positivity or node negativity AND ≥ 1 of the following: * T \> 2 cm * Grade 3 * Presence of lymphovascular invasion * Ki 67 \> 20% * Age 35 years * Hormone receptor negativity (\<10%) * HER2-positive tumor (3+ by IHC or FISH+ according to the American Society of Clinical Oncology guidelines \[i.e., \> 2.2; in case of polysomy, with ≥ 6 gene copies\]) * Estrogen receptor-positive and/or progesterone receptor-positive disease PATIENT CHARACTERISTICS: * Female * Pre- or postmenopausal status * Postmenopausal status defined by ≥ 1 of the following: * At least 60 years of age * Less than 60 years of age and amenorrheic for ≥ 12 months prior to day 1 * Less than 60 years of age and amenorrheic for \< 12 months prior to day 1 with luteinizing hormone and follicle-stimulating hormone values within postmenopausal range OR without a uterus * Prior bilateral oophorectomy * Prior radiation castration with amenorrhea for ≥ 6 months * ECOG performance status 0-1 * Suitable for adjuvant chemotherapy * WBC \> 3,000/mcL * ANC \> 1,500/mcL * Platelet count \>100,000/mcL * Total bilirubin normal * AST and ALT 2.5 times upper limit of normal * Creatinine normal * Cardiac ejection fraction normal as measured by ECHO or MUGA scan * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy * No contraindication to anthracycline, cyclophosphamide, fluorouracil, paclitaxel, or trastuzumab (Herceptin®) treatment * No uncontrolled intercurrent illness including, but not limited to, the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: * See Disease Characteristics * See Patient Characteristics * No prior chemotherapy, endocrine therapy, or radiotherapy * No other concurrent investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Modena: lead

Study Sites (6)

Ospedale Santa Croce

Cuneo, 12100, Italy

RECRUITING

Ospedale Civile di Ivrea

Ivrea, 10015, Italy

RECRUITING

Azienda Ospedaliera - Universitaria di Modena

Modena, 41100, Italy

RECRUITING

Piacenza Hospital

Piacenza, 29100, Italy

RECRUITING

Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino

Turin, 10126, Italy

RECRUITING

Ospedal San Andrea

Vercelli, 13100, Italy

RECRUITING

Related Publications (5)

• Guarneri V, Frassoldati A, Bruzzi P, D'Amico R, Belfiglio M, Molino A, Bertetto O, Cascinu S, Cognetti F, Di Leo A, Pronzato P, Crino L, Agostara B, Conte P. Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). Clin Breast Cancer. 2008 Oct;8(5):453-6. doi: 10.3816/CBC.2008.n.056.

  PMID: 18952561 RESULT

• Conte P, Bisagni G, Piacentini F, Sarti S, Minichillo S, Anselmi E, Aieta M, Gebbia V, Schirone A, Musolino A, Garrone O, Beano A, Rimanti A, Giotta F, Turletti A, Miglietta F, Dieci MV, Vicini R, Balduzzi S, D'Amico R, Guarneri V. Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial. J Clin Oncol. 2023 Nov 10;41(32):4976-4981. doi: 10.1200/JCO.23.00790. Epub 2023 Sep 25.

  PMID: 37748109 DERIVED

• Dieci MV, Bisagni G, Bartolini S, Frassoldati A, Vicini R, Balduzzi S, D'amico R, Conte P, Guarneri V. Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: analysis from the phase III randomized ShortHER trial. NPJ Breast Cancer. 2023 Feb 4;9(1):6. doi: 10.1038/s41523-023-00509-2.

  PMID: 36739285 DERIVED

• Dieci MV, Bisagni G, Brandes AA, Frassoldati A, Cavanna L, Giotta F, Aieta M, Gebbia V, Musolino A, Garrone O, Donadio M, Rimanti A, Beano A, Zamagni C, Soto Parra H, Piacentini F, Danese S, Ferro A, Cagossi K, Sarti S, Gambaro AR, Romito S, Bazan V, Amaducci L, Moretti G, Foschini MP, Balduzzi S, Vicini R, D'Amico R, Griguolo G, Guarneri V, Conte PF. Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial. BMC Med. 2019 Nov 21;17(1):207. doi: 10.1186/s12916-019-1445-z.

  PMID: 31747948 DERIVED

• Conte P, Frassoldati A, Bisagni G, Brandes AA, Donadio M, Garrone O, Piacentini F, Cavanna L, Giotta F, Aieta M, Gebbia V, Molino A, Musolino A, Ferro A, Maltoni R, Danese S, Zamagni C, Rimanti A, Cagossi K, Russo A, Pronzato P, Giovanardi F, Moretti G, Lombardo L, Schirone A, Beano A, Amaducci L, Bajardi EA, Vicini R, Balduzzi S, D'Amico R, Guarneri V. Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER studydouble dagger. Ann Oncol. 2018 Dec 1;29(12):2328-2333. doi: 10.1093/annonc/mdy414.

  PMID: 30219886 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Aromatase Inhibitors; Cyclophosphamide; Docetaxel; Doxorubicin; Epirubicin; Fluorouracil; Paclitaxel; Tamoxifen; Chemotherapy, Adjuvant; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Pier Franco Conte, MD

  Azienda Ospedaliero-Universitaria di Modena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 4, 2008
• First Posted: March 5, 2008
• Study Start: December 1, 2007
• Primary Completion: December 1, 2010
• Last Updated: August 7, 2013

Record last verified: 2009-07

Locations

IT (6)