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

June 14, 2016 updated by: Consorzio Oncotech

A Randomised, Multicentre, Open-label Phase II Trial Investigating Activity of Chemotherapy and Lapatinib and Trastuzumab in Patients With HER2-positive Metastatic Breast Cancer (MBC) Refractory to Anti HER2 Therapies

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The present study is designed to determine the efficacy and safety profile of the combination of lapatinib and trastuzumab (plus endocrinetherapy in ER-positive breast cancer) versus trastuzumab and chemotherapy in heavily pretreated patient population with HER2-positive MBC and to investigate the predictive role of cfDNA for detection of HER2 gene amplification on patients' outcome. The presence of circulating free DNA (cfDNA) for detection of HER2 gene amplification was associated with worse prognosis and seems to allow early response evaluation. However, many aspects of the role of cfDNA detection in patients undergoing molecular target agents such as trastuzumab or lapatinib are not well described. With the availability of improved and standardized techniques for cfDNA detection, it should now be possible to examine several of these important questions within a prospective multicenter study and a striking potential of cfDNA for detection of HER2 gene amplification might enable a more individual and optimized antimetastatic therapy inpatients with cancer.

Study Type

Interventional

Enrollment (Anticipated)

154

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Clinical Research Technology
  • Phone Number: 0039089301545

Study Locations

  • Italy
      • Ancona, Italy, 60020
        • Not yet recruiting
        • A.O.U. Ospedali Riuniti Umberto I
        • Principal Investigator:
          • Stefano Cascinu, MD
      • Aviano, Italy, 33081
        • Recruiting
        • Centro di Riferimento Oncologico
        • Contact:
          • Simon Spazzapan, MD
        • Principal Investigator:
          • SIMON SPAZZAPAN, Md
      • Bologna, Italy, MD
        • Not yet recruiting
        • Policlinico S. Orsola Malpighi
        • Contact:
          • Claudio Zamagni, MD
        • Principal Investigator:
          • Claudio Zamagni, MD
      • Bolzano, Italy, 39100
        • Not yet recruiting
        • Ospedale Centrale di Bolzano
        • Contact:
          • Elisabetta Cretella, MD
        • Principal Investigator:
          • Elisabetta Cretella, MD
      • Brindisi, Italy, 72100
        • Recruiting
        • Presidio Ospedaliero 'Antonio Perrino
        • Contact:
          • Saverio Cinieri, MD
      • Catania, Italy, 95122
        • Recruiting
        • A.O.R.N.A.S. Garibaldi Nesima di Catania
        • Contact:
          • Roberto Bordonaro, MD
        • Principal Investigator:
          • ROBERTO BORDONARO, Md
      • Catania, Italy, 95126
        • Not yet recruiting
        • Humanitas Centro Catanese di Oncologia
        • Contact:
          • Michele Caruso, MD
        • Principal Investigator:
          • MICHELE CARUSO, Md
      • Como, Italy, 22100
        • Not yet recruiting
        • Azienda Ospedaliera S. Anna
        • Contact:
          • Monica Giordano, MD
        • Principal Investigator:
          • Monica Giordano, MD
      • Frosinone, Italy, 03100
        • Not yet recruiting
        • Ospedale 'F. Spaziani'
        • Contact:
          • Teresa Gamucci, MD
      • Genova, Italy, 16132
        • Not yet recruiting
        • I.R.C.C.S. A.O.U. San Martino
        • Contact:
          • Lucia Del Mastro, MD
      • Guastalla, Italy, 42016
        • Not yet recruiting
        • Ospedale Civile di Guastalla
        • Contact:
          • Laura Scaltriti, Md
        • Principal Investigator:
          • Laura Scaltriti, Md
      • Lecce, Italy, 73100
        • Recruiting
        • Ospedale Vito Fazzi
        • Contact:
          • Mariangela Ciccarese, MD
      • Lugo, Italy, 48022
        • Not yet recruiting
        • Ospedale di Lugo - AUSL della Romagna
        • Contact:
          • Michele Gianni Turolla, MD
        • Principal Investigator:
          • Michele Gianni Turolla, Md
      • Meldola, Italy, 47014
        • Not yet recruiting
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
        • Contact:
          • Dino Amadori, MD
      • Milano, Italy, 20162
        • Not yet recruiting
        • Ospedale Niguarda Ca' Granda
        • Principal Investigator:
          • Salvatore Siena, MD
      • Monza, Italy, 20900
        • Recruiting
        • A.O. San Gerardo
        • Contact:
        • Principal Investigator:
          • Marina Elena Cazzaniga, MD
      • Naples, Italy, 80131
        • Recruiting
        • AORN "A. Cardarelli"
        • Contact:
      • Napoli, Italy, 8011
        • Recruiting
        • Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"
      • Napoli, Italy, 80131
        • Not yet recruiting
        • Policlinico SUN
        • Contact:
          • Michele Orditura, MD
      • Napoli, Italy, 80131
        • Recruiting
        • Università degli Studi di Napoli "Federico II"
      • Palermo, Italy, 90127
        • Recruiting
        • A.R.N.A.S. Ospedale Civico e Benfratelli
        • Contact:
          • Vita Leonardi, MD
        • Principal Investigator:
          • VITA LEONARDI, Md
      • Perugia, Italy, 06156
        • Recruiting
        • Ospedale S. Maria Della Misericordia
        • Contact:
          • Anna Maria Mosconi, MD
        • Principal Investigator:
          • Anna Maria Mosconi, MD
      • Pordenone, Italy, 33170
        • Not yet recruiting
        • Azienda Ospedaliera Santa Maria Degli Angeli
        • Contact:
          • Silvana Saracchini, MD
        • Principal Investigator:
          • SILVANA SARACCHINI, Md
      • Ravenna, Italy, 48100
        • Not yet recruiting
        • Ospedale di Ravenna
        • Principal Investigator:
          • Dazzi Claudio, MD
      • Reggio Emilia, Italy, 42123
        • Not yet recruiting
        • Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
      • Rimini, Italy, 47923
        • Not yet recruiting
        • Ospedale Infermi di Rimini
        • Contact:
          • Lorenzo Gianni, MD
        • Principal Investigator:
          • Lorenzo Gianni, MD
      • Roma, Italy, 00128
        • Recruiting
        • Policlinico Universitario Campus Biomedico
        • Contact:
          • Giuseppe Tonini, MD
        • Principal Investigator:
          • Giuseppe Tonini, MD
      • Roma, Italy, 00144
        • Recruiting
        • Istituto Regina Elena per lo studio e la cura dei tumori
        • Principal Investigator:
          • Cognetti Francesco, MD
      • Salerno, Italy, 84126
        • Not yet recruiting
        • Ospedale G. Da Procida
        • Contact:
          • Maria Luisa Barzelloni, MD
        • Principal Investigator:
          • MARIA LUISA BARZELLONI, Md
      • Sassari, Italy, 07100
        • Recruiting
        • Ospedale Civile di Sassari SS Annunaziata
        • Contact:
          • Nina Olmeo, MD
        • Principal Investigator:
          • Nina Olmeo, MD
      • Sora, Italy, 03039
        • Recruiting
        • Ospedale 'SS. Trinità'
        • Contact:
          • Teresa Gamucci, MD
      • Terni, Italy, 05100
        • Recruiting
        • Azienda Ospedaliera S.Maria di Terni
        • Contact:
          • Fauso Roila, Md
        • Principal Investigator:
          • Fausto Roila, MD
      • Torino, Italy, 10126
        • Not yet recruiting
        • A.O.U. San Giovanni Battista di Torino
        • Contact:
          • Mario Airoldi, MD
        • Principal Investigator:
          • Mario Airoldi, MD
      • Udine, Italy, 33100
        • Recruiting
        • A.O.U. Santa Maria della Misericordia di Udine
      • Varese, Italy, 21100
        • Not yet recruiting
        • A.O. Ospedale di Circolo e Fondazione Macchi
        • Contact:
          • Giovanni Giardina, MD
        • Principal Investigator:
          • Giovanni Giardina, MD
      • Verona, Italy, 37024
        • Not yet recruiting
        • Ospedale Sacro Cuore Don Calabria
        • Contact:
          • Stefania Gori, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: 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).
Other Names:
  • Tyverb
Drug: 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 Names:
  • Herceptin
Experimental: 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.
Drug: 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 Names:
  • Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Benefit Rate
Time Frame: Clinical Benefit Rate is defined as confirmed complete response plus partial response at any time, plus stable disease up to 24 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months
Second-line progression-free survival, defined as the time from first dosing to the first documented disease progression or death from any cause, whichever occurs first.
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
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months
OS is defined as the time from first dosing in second line to death from any cause.
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
Time Frame: 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 of second line treatment will be evaluated by the frequency of AEs and SAEs, cardiac events, clinically significant abnormal laboratory tests, vital signs, and ECOG PS. All patients who received at least one dose of study treatment will be included in the safety analysis.
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
Time Frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months
QoL and symptom control will be assessed using the FACT-B questionnaire.
Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Consorzio Oncotech

Collaborators

Clinical Research Technology S.r.l.

Investigators

  • Principal Investigator: Grazia Arpino, MD, Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Anticipated)

October 1, 2017

Study Completion (Anticipated)

October 1, 2017

Study Registration Dates

First Submitted

September 9, 2014

First Submitted That Met QC Criteria

September 11, 2014

First Posted (Estimate)

September 12, 2014

Study Record Updates

Last Update Posted (Estimate)

June 15, 2016

Last Update Submitted That Met QC Criteria

June 14, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIM12-TYPHER
  • 2013-005044-29 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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