Safety and QoL of Trastuzumab With Lapatinib or Chemiotherapy in MBC and HER2+ Patients Refractory to Anti HER2 Therapies

NCT02238509 | Unknown Phase 2 DMC

• 2 other identifiers: GIM12-TYPHER2013-005044-29
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 36

Brief Summary

Recent clinical studies have shown that the combination of lapatinib and trastuzumab has superior antitumor activity compared to either single drug in both neoadjuvant and metastatic setting and is well tolerated. According to this evidence, the combination of lapatinib and trastuzumab today offers a valid chemotherapy-free option, primarily for patients with pre-treated HER2-positive MBC

Conditions

Metastatic Breast Cancer

Keywords

Breast cancer; HER2 Positive; HER2+; MBC; Metastatic; Metastatic breast cancer; Chemotherapy; Lapatinib; Trastuzumab; anti HER2 therapies

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate

  To evaluate clinical benefit rate (CBR) for patients treated with lapatinib and trastuzumab and for patients treated with trastuzumab and chemotherapy. CBR is defined as: confirmed complete response (CR) plus partial response (PR) at any time, plus stable disease (SD) for 24 weeks

  Clinical Benefit Rate is defined as confirmed complete response plus partial response at any time, plus stable disease up to 24 weeks

Secondary Outcomes (4)

• Progression free survival

  Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months

• Overall Survival

  Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months

• Safety and tolerability

  Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months

• Quality of life

  Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months

Study Arms (2)

lapatinib and trastuzumab

EXPERIMENTAL

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).

Drug: Lapatinib; Drug: Trastuzumab

trastuzumab plus chemotherapy

EXPERIMENTAL

ARM B: Trastuzumab plus chemotherapy (control arm). Any type of chemotherapy in combination with trastuzumab will be allowed at the physician's discretion.

Drug: Trastuzumab

Interventions

Lapatinib DRUG

ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).

Also known as: Tyverb

lapatinib and trastuzumab

Trastuzumab DRUG

ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).

Also known as: Herceptin

lapatinib and trastuzumab; trastuzumab plus chemotherapy

Eligibility Criteria

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

You may qualify if:

• Histological or cytological confirmed and documented adenocarcinoma of the breast with metastatic disease
• 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

You may not qualify if:

• History of persistent Grade ≥ 2 hematologic toxicity resulting from previous systemic therapy
• 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

Sponsors & Collaborators

• Consorzio Oncotech: lead
• Clinical Research Technology S.r.l.: collaborator

Study Sites (36)

A.O.U. Ospedali Riuniti Umberto I

Ancona, 60020, Italy

NOT YET RECRUITING

Centro di Riferimento Oncologico

Aviano, 33081, Italy

RECRUITING

Policlinico S. Orsola Malpighi

Bologna, MD, Italy

NOT YET RECRUITING

Ospedale Centrale di Bolzano

Bolzano, 39100, Italy

NOT YET RECRUITING

Presidio Ospedaliero 'Antonio Perrino

Brindisi, 72100, Italy

RECRUITING

A.O.R.N.A.S. Garibaldi Nesima di Catania

Catania, 95122, Italy

RECRUITING

Humanitas Centro Catanese di Oncologia

Catania, 95126, Italy

NOT YET RECRUITING

Azienda Ospedaliera S. Anna

Como, 22100, Italy

NOT YET RECRUITING

Ospedale 'F. Spaziani'

Frosinone, 03100, Italy

NOT YET RECRUITING

I.R.C.C.S. A.O.U. San Martino

Genova, 16132, Italy

NOT YET RECRUITING

Ospedale Civile di Guastalla

Guastalla, 42016, Italy

NOT YET RECRUITING

Ospedale Vito Fazzi

Lecce, 73100, Italy

RECRUITING

Ospedale di Lugo - AUSL della Romagna

Lugo, 48022, Italy

NOT YET RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

NOT YET RECRUITING

Ospedale Niguarda Ca' Granda

Milan, 20162, Italy

NOT YET RECRUITING

A.O. San Gerardo

Monza, 20900, Italy

RECRUITING

AORN "A. Cardarelli"

Naples, 80131, Italy

RECRUITING

Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"

Napoli, 8011, Italy

RECRUITING

Policlinico SUN

Napoli, 80131, Italy

NOT YET RECRUITING

Università degli Studi di Napoli "Federico II"

Napoli, 80131, Italy

RECRUITING

A.R.N.A.S. Ospedale Civico e Benfratelli

Palermo, 90127, Italy

RECRUITING

Ospedale S. Maria della Misericordia

Perugia, 06156, Italy

RECRUITING

Azienda Ospedaliera Santa Maria degli Angeli

Pordenone, 33170, Italy

NOT YET RECRUITING

Ospedale di Ravenna

Ravenna, 48100, Italy

NOT YET RECRUITING

Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia

Reggio Emilia, 42123, Italy

NOT YET RECRUITING

Ospedale Infermi di Rimini

Rimini, 47923, Italy

NOT YET RECRUITING

Policlinico Universitario Campus Biomedico

Roma, 00128, Italy

RECRUITING

Istituto Regina Elena per lo studio e la cura dei tumori

Roma, 00144, Italy

RECRUITING

Ospedale G. Da Procida

Salerno, 84126, Italy

NOT YET RECRUITING

Ospedale Civile di Sassari SS Annunaziata

Sassari, 07100, Italy

RECRUITING

Ospedale 'SS. Trinità'

Sora, 03039, Italy

RECRUITING

Azienda Ospedaliera S.Maria di Terni

Terni, 05100, Italy

RECRUITING

A.O.U. San Giovanni Battista di Torino

Torino, 10126, Italy

NOT YET RECRUITING

A.O.U. Santa Maria della Misericordia di Udine

Udine, 33100, Italy

RECRUITING

A.O. Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

NOT YET RECRUITING

Ospedale Sacro Cuore Don Calabria

Verona, 37024, Italy

NOT YET RECRUITING

Related Publications (15)

• 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.

  PMID: 16458110 BACKGROUND

• 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.

  PMID: 16683005 BACKGROUND

• 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.

  PMID: 21088439 BACKGROUND

• 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.

  PMID: 17192538 BACKGROUND

• 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.

  PMID: 20838057 BACKGROUND

• 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.

  PMID: 21741829 BACKGROUND

• Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. doi: 10.1200/JCO.2008.21.4437. Epub 2010 Feb 1.

  PMID: 20124187 BACKGROUND

• 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.

  PMID: 21406472 BACKGROUND

• 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.

  PMID: 19786658 BACKGROUND

• 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.

  PMID: 21427727 BACKGROUND

• 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.

  PMID: 16236738 BACKGROUND

• 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.

  PMID: 22123186 BACKGROUND

• 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.

  PMID: 16258083 BACKGROUND

• 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.

  PMID: 11248153 BACKGROUND

• Rusnak DW, Lackey K, Affleck K, Wood ER, Alligood KJ, Rhodes N, Keith BR, Murray DM, Knight WB, Mullin RJ, Gilmer TM. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94.

  PMID: 12467226 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Grazia Arpino, MD

  Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Research Technology

CONTACT

0039089301545

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 12, 2014
• Study Start: November 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: June 15, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (36)