Trastuzumab for 6 Months or 1 Year in Treating Women With Nonmetastatic Breast Cancer That Can Be Removed By Surgery

• ClinicalTrials.gov Identifier: NCT00381901
• Recruitment Status: Completed
• First Posted: September 28, 2006
• Last Update Posted: May 13, 2011
• Sponsor: National Cancer Institute, France
• Information provided by: National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: September 26, 2006
• First Posted Date: September 28, 2006
• Last Update Posted Date: May 13, 2011
• Study Start Date: May 2006
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 4, 2006): Time to recurrence
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: December 4, 2006)

• Cardiotoxicity as measured by LVEF
• Distant metastasis-free survival
• Overall survival

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trastuzumab for 6 Months or 1 Year in Treating Women With Nonmetastatic Breast Cancer That Can Be Removed By Surgery
• Official Title: Protocol of Herceptin Adjuvant With Reduced Exposure, a Randomised Comparison of 6 Months vs 12 Months in All Women Receiving Adjuvant Herceptin [PHARE]

Brief Summary

RATIONALE: 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 whether giving trastuzumab for 6 months is as effective as giving trastuzumab for 1 year in treating patients with breast cancer.

PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works when given for 6 months compared to 12 months in treating women with nonmetastatic breast cancer that can be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• Compare the disease-free survival of women with nonmetastatic, resectable breast cancer treated with adjuvant trastuzumab (Herceptin®) for 6 months vs 12 months.

Secondary

• Compare cardiotoxicity in patients receiving these regimens.
• Compare the cardiotoxicity and disease-free survival of patients receiving concurrent trastuzumab and chemotherapy vs sequential administration.
• Correlate HER-2 polymorphism with disease-free survival/cardiotoxicity in these patients.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, modality of adjuvant chemotherapy (concurrent vs sequential), and adjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I (control arm, 12-month therapy): Patients continue to receive trastuzumab (Herceptin®) IV until a total of 12 months of therapy is completed in the absence of disease progression or unacceptable toxicity.
• Arm II (experimental arm, 6-month therapy): Patients continue to receive trastuzumab* IV until a total of 6 months of therapy is completed in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients who have already finished 6 months of trastuzumab at randomization do not receive further trastuzumab.

Some patients undergo blood collection for HER-2 polymorphism analysis.

After completion of study therapy, patients are followed periodically for approximately 5 years.

PROJECTED ACCRUAL: A total of 7,000 patients will be accrued for this study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Biological: trastuzumab
• Genetic: polymorphism analysis
• Procedure: adjuvant therapy

• Study Arms: Not Provided

Publications *

• Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espie M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Venat-Bouvet L, Cany L, Catala S, Khayat D, Gambotti L, Pauporte I, Faure-Mercier C, Paget-Bailly S, Henriques J, Grouin JM; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial. Lancet. 2019 Jun 29;393(10191):2591-2598. doi: 10.1016/S0140-6736(19)30653-1. Epub 2019 Jun 6.
• Jacquinot Q, Paget-Bailly S, Fumoleau P, Romieu G, Pierga JY, Espie M, Lortholary A, Nabholtz JM, Mercier CF, Pauporte I, Henriques J, Pivot X. Fluctuation of the left ventricular ejection fraction in patients with HER2-positive early breast cancer treated by 12 months of adjuvant trastuzumab. Breast. 2018 Oct;41:1-7. doi: 10.1016/j.breast.2018.06.001. Epub 2018 Jun 15.
• Curtit E, Pivot X, Henriques J, Paget-Bailly S, Fumoleau P, Rios M, Bonnefoi H, Bachelot T, Soulie P, Jouannaud C, Bourgeois H, Petit T, Tennevet I, Assouline D, Mathieu MC, Jacquin JP, Lavau-Denes S, Darut-Jouve A, Ferrero JM, Tarpin C, Levy C, Delecroix V, Trillet-Lenoir V, Cojocarasu O, Meunier J, Pierga JY, Kerbrat P, Faure-Mercier C, Blanche H, Sahbatou M, Boland A, Bacq D, Besse C, Thomas G, Deleuze JF, Pauporte I, Romieu G, Cox DG. Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes. Breast Cancer Res. 2017 Aug 22;19(1):98. doi: 10.1186/s13058-017-0888-4.
• Pivot X, Fumoleau P, Pierga JY, Delaloge S, Bonnefoi H, Bachelot T, Jouannaud C, Bourgeois H, Rios M, Soulie P, Jacquin JP, Lavau-Denes S, Kerbrat P, Cox D, Faure-Mercier C, Pauporte I, Gligorov J, Curtit E, Henriques J, Paget-Bailly S, Romieu G. Superimposable outcomes for sequential and concomitant administration of adjuvant trastuzumab in HER2-positive breast cancer: Results from the SIGNAL/PHARE prospective cohort. Eur J Cancer. 2017 Aug;81:151-160. doi: 10.1016/j.ejca.2017.05.020. Epub 2017 Jun 16.
• Pivot X, Suter T, Nabholtz JM, Pierga JY, Espie M, Lortholary A, Khayat D, Pauporte I, Romieu G, Kramar A, Fumoleau P. Cardiac toxicity events in the PHARE trial, an adjuvant trastuzumab randomised phase III study. Eur J Cancer. 2015 Sep;51(13):1660-6. doi: 10.1016/j.ejca.2015.05.028. Epub 2015 Jul 7.
• Kramar A, Bachelot T, Madrange N, Pierga JY, Kerbrat P, Espie M, Fumoleau P, Pauporte I, Khayat D, Romieu G, Pivot X. Trastuzumab duration effects within patient prognostic subgroups in the PHARE trial. Ann Oncol. 2014 Aug;25(8):1563-70. doi: 10.1093/annonc/mdu177. Epub 2014 May 14.
• Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espie M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Tubiana-Mathieu N, Cany L, Catala S, Khayat D, Pauporte I, Kramar A; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013 Jul;14(8):741-8. doi: 10.1016/S1470-2045(13)70225-0. Epub 2013 Jun 11.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: December 2, 2009): 3400
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

• Nonmetastatic disease

  • Positive or negative axillary nodes
  • Tumor size ≥ 10 mm
• Resectable disease
• Must have received ≥ 4 courses of chemotherapy for this disease

• A 12-month adjuvant treatment with trastuzumab (Herceptin®) has been initiated

  • Informed consent form must be signed between the third and sixth months of trastuzumab therapy

• Overexpression of HER-2 in the invasive component of the primary tumor as indicated by 1 of the following:

  • 3+ by immunohistochemistry (IHC)
  • 2+ by IHC and confirmation by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Menopausal status not specified
• LVEF considered favorable for continuing trastuzumab treatment as measured by echocardiography or MUGA at 2-4 months after beginning adjuvant trastuzumab

• No serious cardiac illness or medical condition precluding trastuzumab treatment, including any of the following:

  • History of documented congestive heart failure
  • High-risk uncontrolled arrhythmias
  • Angina pectoris requiring antianginal medication
  • Severe dyspnea at rest or oxygen-dependent
• No known hypersensitivity to trastuzumab, murine proteins, or any of the excipients
• Not pregnant or nursing
• No social, geographical, or psychological condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Other prior anti-HER-2 therapy allowed
• No prior trastuzumab other than initiation of trastuzumab adjuvant therapy

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00381901
• Other Study ID Numbers: CDR0000509793; INCA-PHARE; INCA-RECF0146; EUDRACT-2006-000070-67
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: National Cancer Institute, France
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Xavier Pivot, MD, PhD; Hopital Jean Minjoz

• PRS Account: National Cancer Institute (NCI)
• Verification Date: July 2009