Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02238509
Recruitment Status : Unknown
Verified June 2016 by Consorzio Oncotech.
Recruitment status was:  Recruiting
First Posted : September 12, 2014
Last Update Posted : June 15, 2016
Sponsor:
Collaborator:
Clinical Research Technology S.r.l.
Information provided by (Responsible Party):
Consorzio Oncotech

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Lapatinib Drug: Trastuzumab Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 154 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : November 2014
Estimated Primary Completion Date : October 2017
Estimated Study Completion Date : October 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: 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 Name: Herceptin


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02238509


Contacts
Layout table for location contacts
Contact: Clinical Research Technology 0039089301545

Locations
Show Show 36 study locations
Sponsors and Collaborators
Consorzio Oncotech
Clinical Research Technology S.r.l.
Investigators
Layout table for investigator information
Principal Investigator: Grazia Arpino, MD Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Layout table for additonal information
Responsible Party: Consorzio Oncotech
ClinicalTrials.gov Identifier: NCT02238509    
Other Study ID Numbers: GIM12-TYPHER
2013-005044-29 ( EudraCT Number )
First Posted: September 12, 2014    Key Record Dates
Last Update Posted: June 15, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Consorzio Oncotech:
Breast cancer
HER2 Positive
HER2+
MBC
Metastatic
 Metastatic breast cancer
Chemotherapy
Lapatinib
Trastuzumab
anti HER2 therapies
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
 Lapatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action