Safety and QoL of Trastuzumab With Lapatinib or Chemiotherapy in MBC and HER2+ Patients Refractory to Anti HER2 Therapies
NCT ID: NCT02238509
Last Updated: 2016-06-15
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2
154 participants
INTERVENTIONAL
2014-11-30
2017-10-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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lapatinib and trastuzumab
ARM A: Lapatinib and trastuzumab (experimental arm). Patients with hormone receptor (HR) positive breast cancer will also receive endocrine therapy at the physician's discretion (preferred choice with fulvestrant).
Lapatinib
ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).
Trastuzumab
ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).
trastuzumab plus chemotherapy
ARM B: Trastuzumab plus chemotherapy (control arm). Any type of chemotherapy in combination with trastuzumab will be allowed at the physician's discretion.
Trastuzumab
ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).
Interventions
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Lapatinib
ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).
Trastuzumab
ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* The original tumour specimen must be HER2 IHC 3+ positive or, in case of IHC 2+
* Age ≥18
* Life expectancy of \>12 weeks
* ECOG PS 0-1
* Measurable disease as defined by RECIST1.1 criteria
* All patients must have received prior anthracycline-and taxane-based regimens as well as trastuzumab based regimens in either the adjuvant or the metastatic setting. Patients must have been already treated with at least one line of the anti HER2 inhibitor therapy lapatinib for their metastatic breast cancer. A maximum of three previous lines of anti-HER-2 therapies in the metastatic setting are allowed.
* Adequate haematological function as defined by: ANC 1.5 x 109/L, platelet count 100 x 109/L, haemoglobin 10 g/dL.
* Adequate renal function, as defined by: creatinine 1.5 x UNL
* Adequate hepatobiliary function, as defined by the following baseline liver function tests: total serum bilirubin 1.5 upper normal limit (UNL); alanine amino transferase (ALT), aspartate amino transferase (AST) 2.5xUNL; alkaline phosphatase (AP) 2.5xUNL; if total alkaline phosphatase (AP) \> 2.5xUNL, alkaline phosphatase liver fraction must be 2.5xUNL
* Adequate contraception for all fertile patients
* Negative pregnancy test.
* Postmenopausal women fulfilling any of the NCCN criteria may be included.
* Left ventricular ejection fraction (LVEF) ≥50% during a baseline period of 28 days, as determined by either echocardiography (ECHO) or multi gated acquisition (MUGA) scan.
* Signed, written informed consent
Exclusion Criteria
* Current peripheral neuropathy of NCI-CTCAE, Version 3.0, Grade ≥ 3 at randomization
* History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
* Bone-only disease, unless a measurable lesion is evident as determined by RECIST v1.1
* Bone scan, PET scan or plain films are not considered adequate imaging techniques to measure bone lesions. ve
* Blastic bone lesions are non-measurable.
* Uncontrolled hypertension (systolic \>150 mm Hg and/or diastolic \>100 mm Hg) or clinically significant (i.e. active) cardiovascular disease.
* Current dyspnoea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy.
* Inadequate organ function, evidenced by the following laboratory results within 28 days prior to randomization.
* Current severe, uncontrolled systemic disease
* Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
* History of receiving any investigational treatment within 28 days of randomization
* Current known infection with HIV, HBV, or HCV
* Receipt of IV antibiotics for infection within 14 days of randomization
* Known hypersensitivity to any of the study drugs
* Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
* Lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medications
* Concurrent interventional or non-interventional studies
18 Years
FEMALE
No
Sponsors
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Clinical Research Technology S.r.l.
INDUSTRY
Consorzio Oncotech
OTHER
Responsible Party
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Principal Investigators
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Grazia Arpino, MD
Role: PRINCIPAL_INVESTIGATOR
Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"
Locations
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A.O.U. Ospedali Riuniti Umberto I
Ancona, , Italy
Centro di Riferimento Oncologico
Aviano, , Italy
Policlinico S. Orsola Malpighi
Bologna, , Italy
Ospedale Centrale di Bolzano
Bolzano, , Italy
Presidio Ospedaliero 'Antonio Perrino
Brindisi, , Italy
A.O.R.N.A.S. Garibaldi Nesima di Catania
Catania, , Italy
Humanitas Centro Catanese di Oncologia
Catania, , Italy
Azienda Ospedaliera S. Anna
Como, , Italy
Ospedale 'F. Spaziani'
Frosinone, , Italy
I.R.C.C.S. A.O.U. San Martino
Genova, , Italy
Ospedale Civile di Guastalla
Guastalla, , Italy
Ospedale Vito Fazzi
Lecce, , Italy
Ospedale di Lugo - AUSL della Romagna
Lugo, , Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, , Italy
Ospedale Niguarda Ca' Granda
Milan, , Italy
A.O. San Gerardo
Monza, , Italy
AORN "A. Cardarelli"
Naples, , Italy
Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"
Napoli, , Italy
Policlinico SUN
Napoli, , Italy
Università degli Studi di Napoli "Federico II"
Napoli, , Italy
A.R.N.A.S. Ospedale Civico e Benfratelli
Palermo, , Italy
Ospedale S. Maria della Misericordia
Perugia, , Italy
Azienda Ospedaliera Santa Maria degli Angeli
Pordenone, , Italy
Ospedale di Ravenna
Ravenna, , Italy
Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
Reggio Emilia, , Italy
Ospedale Infermi di Rimini
Rimini, , Italy
Policlinico Universitario Campus Biomedico
Roma, , Italy
Istituto Regina Elena per lo studio e la cura dei tumori
Roma, , Italy
Ospedale G. Da Procida
Salerno, , Italy
Ospedale Civile di Sassari SS Annunaziata
Sassari, , Italy
Ospedale 'SS. Trinità'
Sora, , Italy
Azienda Ospedaliera S.Maria di Terni
Terni, , Italy
A.O.U. San Giovanni Battista di Torino
Torino, , Italy
A.O.U. Santa Maria della Misericordia di Udine
Udine, , Italy
A.O. Ospedale di Circolo e Fondazione Macchi
Varese, , Italy
Ospedale Sacro Cuore Don Calabria
Verona, , Italy
Countries
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Central Contacts
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Clinical Research Technology
Role: CONTACT
Facility Contacts
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Stefano Cascinu, MD
Role: primary
Simon Spazzapan, MD
Role: primary
Claudio Zamagni, MD
Role: primary
Elisabetta Cretella, MD
Role: primary
Saverio Cinieri, MD
Role: primary
Roberto Bordonaro, MD
Role: primary
Michele Caruso, MD
Role: primary
Monica Giordano, MD
Role: primary
Teresa Gamucci, MD
Role: primary
Lucia Del Mastro, MD
Role: primary
Laura Scaltriti, Md
Role: primary
Mariangela Ciccarese, MD
Role: primary
Michele Gianni Turolla, MD
Role: primary
Dino Amadori, MD
Role: primary
Salvatore Siena, Md
Role: primary
Michele De Laurentiis, MD
Role: primary
Michele Orditura, MD
Role: primary
Grazia Arpino, MD
Role: primary
Vita Leonardi, MD
Role: primary
Anna Maria Mosconi, MD
Role: primary
Silvana Saracchini, MD
Role: primary
Claudio Dazzi, MD
Role: primary
Corrado Boni, MD
Role: primary
Lorenzo Gianni, MD
Role: primary
Giuseppe Tonini, Md
Role: primary
Francesco Cognetti, Md
Role: primary
Maria Luisa Barzelloni, MD
Role: primary
Nina Olmeo, MD
Role: primary
Teresa Gamucci, MD
Role: primary
Fauso Roila, Md
Role: primary
Mario Airoldi, MD
Role: primary
fabio Puglisi, MD
Role: primary
Giovanni Giardina, MD
Role: primary
Stefania Gori, MD
Role: primary
References
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Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006 Feb 8;232(2):123-38. doi: 10.1016/j.canlet.2005.01.041.
Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006 May;3(5):269-80. doi: 10.1038/ncponc0509.
Jagiello-Gruszfeld A, Tjulandin S, Dobrovolskaya N, Manikhas A, Pienkowski T, DeSilvio M, Ridderheim M, Abbey R. A single-arm phase II trial of first-line paclitaxel in combination with lapatinib in HER2-overexpressing metastatic breast cancer. Oncology. 2010;79(1-2):129-35. doi: 10.1159/000318043. Epub 2010 Nov 22.
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
Clemens M, Eidtmann H, Nitz U, Niederle N, du Bois A, Grischke EM, Hinke A, von Minckwitz G. Trastuzumab single-drug therapy after failure of cytotoxic treatment for metastatic breast cancer. Onkologie. 2010;33(8-9):425-30. doi: 10.1159/000318144. Epub 2010 Jul 27.
von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Luck HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. doi: 10.1016/j.ejca.2011.06.021. Epub 2011 Jul 7.
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Wu Y, Amonkar MM, Sherrill BH, O'Shaughnessy J, Ellis C, Baselga J, Blackwell KL, Burstein HJ. Impact of lapatinib plus trastuzumab versus single-agent lapatinib on quality of life of patients with trastuzumab-refractory HER2+ metastatic breast cancer. Ann Oncol. 2011 Dec;22(12):2582-2590. doi: 10.1093/annonc/mdr014. Epub 2011 Mar 15.
Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. doi: 10.1200/JCO.2009.23.3734. Epub 2009 Sep 28.
Page K, Hava N, Ward B, Brown J, Guttery DS, Ruangpratheep C, Blighe K, Sharma A, Walker RA, Coombes RC, Shaw JA. Detection of HER2 amplification in circulating free DNA in patients with breast cancer. Br J Cancer. 2011 Apr 12;104(8):1342-8. doi: 10.1038/bjc.2011.89. Epub 2011 Mar 22.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. doi: 10.1056/NEJMoa052122.
Wang YC, Morrison G, Gillihan R, Guo J, Ward RM, Fu X, Botero MF, Healy NA, Hilsenbeck SG, Phillips GL, Chamness GC, Rimawi MF, Osborne CK, Schiff R. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers--role of estrogen receptor and HER2 reactivation. Breast Cancer Res. 2011;13(6):R121. doi: 10.1186/bcr3067. Epub 2011 Nov 28.
Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, Shannon RP, Swain SM, Brown A, Fehrenbacher L, Vogel VG, Seay TE, Rastogi P, Mamounas EP, Wolmark N, Bryant J. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005 Nov 1;23(31):7811-9. doi: 10.1200/JCO.2005.02.4091.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. doi: 10.1056/NEJM200103153441101.
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Other Identifiers
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2013-005044-29
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GIM12-TYPHER
Identifier Type: -
Identifier Source: org_study_id
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