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Kadcyla In pAtients With bRAin Metastasis (KIARA)

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: NCT03203616
Recruitment Status : Withdrawn (As most HER2+ patient develop brain mets while on/after having received TDM1, it has proven to be an insurmountable challenge to recruit patients)
First Posted : June 29, 2017
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute

Brief Summary:
Women with breast cancer often develop metastases in the brain. Currently, treatment of these metastases is difficult and relies on radiotherapy or surgery which often fail. Therefore, development of new methods of treatment for breast cancer with brain metastasis is very important. T-DM1 is a drug that is already in everyday use for a specific type of breast cancer called HER2-positive breast cancer. The objective of this study is to investigate whether T-DM1 is also effective in brain metastasis and can help patients to live longer and better

Condition or disease Intervention/treatment Phase
Metastatic HER2-positive Breast Cancer With Brain Metastasis Drug: KADCYLA 160 MG Injection Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Non-randomised, Open-label, Single Agent Phase II Study to Determine the Clinical Benefit of Trastuzumab Emtansine (T-DM1) in HER2-positive Metastatic Breast Cancer Patients With Brain Metastasis
Actual Study Start Date : February 23, 2018
Actual Primary Completion Date : August 27, 2018
Actual Study Completion Date : August 27, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Kadcyla (T-DM1)
trastuzumab emtansine given every 3 weeks at the standard dose (3.6 mg/kg) via intravenous infusion, until disease progression, intolerable toxicity or consent withdrawal. A median of 9 cycles per patient is expected
Drug: KADCYLA 160 MG Injection
Kadcyla 160Mg Powder for Injection: 3.6 mg/kg iv every 3 weeks
Other Names:
  • T-DM1
  • trastuzumab emtansine




Primary Outcome Measures :
  1. Clinical Benefit (CB) [ Time Frame: 9 weeks ]
    defined as complete response plus partial response plus stable disease in the brain, measured by RECIST 1.1, as determined by the local investigators.


Secondary Outcome Measures :
  1. CB in the brain RECIST 1.1 [ Time Frame: 9 weeks ]
    measured by RECIST 1.1 criteria, as determined by central evaluation

  2. CB in the brain RANO [ Time Frame: 9 weeks ]
    measured by RANO brain metastases criteria, as determined by the local investigators

  3. General and cardiac-specific safety [ Time Frame: up to 30 days after last treatment administration ]
    AEs and SAEs according NCI-CTCAE v4.03

  4. CB: Systemic [ Time Frame: 9 weeks ]
    defined as complete response plus partial response plus stable disease in non brain areas

  5. CB: bi-compartmental [ Time Frame: 9 weeks ]
    defined as complete response plus partial response plus stable disease in the whole body

  6. Overall Response (OR) in the brain [ Time Frame: 9 weeks ]
    defined as complete response plus partial response in brain

  7. Overall Response (OR) systemic [ Time Frame: 9 weeks ]
    defined as complete response plus partial response in non brain

  8. Overall Response (OR) bi-compartmental [ Time Frame: 9 weeks ]
    defined as complete response plus partial response in the whole body

  9. Best Response (BR) in the brain [ Time Frame: 1 year ]
    defined as the best obtained response in the brain

  10. Best Response (BR) systemic [ Time Frame: 1 year ]
    defined as the best obtained response in the non brain

  11. Best Response (BR) bi-compartmental [ Time Frame: 1 year ]
    defined as the best obtained response in the whole body

  12. Brain Progression free survival (PFS) [ Time Frame: 1 year ]
    defined as time between enrolment in the study and progression in the brain

  13. Systemic PFS [ Time Frame: 1 year ]
    defined as time between enrolment in the study and progression in areas other than the brain

  14. Bi-compartmental PFS [ Time Frame: 1 year ]
    defined as time between enrolment in the study and progression of disease

  15. Duration of response in the brain [ Time Frame: 1 year ]
    defined as time from documentation of tumour response in the brain (PR or CR) to disease progression in the brain

  16. Duration of response systemic [ Time Frame: 1 year ]
    systemic defined as time from documentation of non-brain tumour response (PR or CR) to non-brain progression

  17. Duration of response bi-compartmental [ Time Frame: 1 year ]
    Bi-compartmental defined as time between response and progression

  18. Duration of Clinical Benefit (DCB) in the brain [ Time Frame: 1 year ]
    defined as the time elapsed between determination of SD, PR or CR and determination of disease progression in the brain

  19. Duration of Clinical Benefit (DCB) systemic [ Time Frame: 1 year ]
    defined as the time elapsed between determination of SD, PR or CR and determination of systemic disease progression

  20. Duration of Clinical Benefit (DCB) bi-compartmental [ Time Frame: 1 year ]
    defined as the time elapsed between determination of SD, PR or CR and determination of bi-compartmental disease progression

  21. Overall survival [ Time Frame: 1 year ]
    defined as time between enrolment in the study and death

  22. Quality of life [ Time Frame: 1 year ]
    Quality of life will be assessed using the EORTC validated questionnaires



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.


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

Inclusion Criteria:

Participants must meet all these criteria in order to be eligible for the study:

General Criteria:

  • Female patients (≥ 18 years);
  • Histologically confirmed HER2-positive breast cancer patients (IHC 3+ and/or ISH positive);
  • Patients should have previously received trastuzumab and a taxane, separately or in combination. Patients should have either received prior therapy for locally advanced or metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy;
  • At least one measurable brain metastasis as defined by RECIST 1.1 (≥ 10 mm);
  • Any hormone receptor status;
  • Predicted life expectancy > 3 months;
  • Any previous anti-HER2 therapies are allowed, other than T-DM1;
  • ECOG performance score 0-2;
  • No significant cardiac history and a current LVEF ≥ 50%. LVEF should be determined within 21 days before enrolment;
  • Adequate organ function, evidenced by the following laboratory results. Exams are to be performed at a maximum of 7 days before enrolment.

    • Absolute neutrophil count > 1,500 cells/mm3 without growth factor support (14 days after last peg-filgrastrim, 7 days for regular filgrastrim).
    • Platelet count > 100,000 cells/mm3 without transfusion 2 weeks prior assessment
    • Hemoglobin > 9 g/dL without transfusion 2 weeks prior assessment.
    • Aspartate aminotransferase and alanine aminotransferase < 2.5 x upper limit of normal (ULN).
    • Total bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert's syndrome, in which case direct (conjugated) bilirubin level needs to be within normal limits.
    • Serum alkaline phosphatase ≤ 2.5 x ULN. Patients with bone metastases: alkaline phosphatase ≤ 5 x ULN.
    • Serum creatinine < 2.0 mg/dL or < 177 μmol/L.
    • International normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time < 1.5 ULN unless patient receiving anticoagulant therapy
  • For women of childbearing potential a serum pregnancy test will be done up to 7 days before enrolment (and it must be negative) and an agreement to use one highly-effective form of non-hormonal contraception (true abstinence, vasectomy, oophorectomy/hysterectomy, IUD) or two effective forms of non-hormonal contraception (e.g., condoms plus spermicidal agent) at study entry (to be put in place within 2 weeks prior to enrolment), during the administration of T-DM1 and for 7 months after the last administration of T-DM1 will be obtained
  • Signed informed consent obtained before any study-specific procedure;
  • Able and willing to comply with the protocol; including the willingness to provide samples (primary if available and blood) for translational research.

Cohort 1 additional specific criteria:

  • No corticosteroids at enrolment
  • Oligosymptomatic or asymptomatic brain metastases not requiring immediate local therapy.

Cohort 2 additional specific criteria:

  • Radiologically confirmed brain progression after previous local therapy (neurosurgery, radiosurgery to the brain, stereotactic radiotherapy to the brain, or whole brain radiotherapy) with at least 3 months between end of local therapy and brain progression.
  • Decreasing corticosteroid dose or stable dose for at least one week prior to enrolment

Exclusion Criteria:

Patients who exhibit any of the following conditions at screening will be ineligible for admission into the study:

General Criteria:

  • Single brain metastasis with indication of surgical resection
  • Pregnant or breast-feeding women
  • Documented leptomeningeal disease
  • Having received any investigational therapy within ≤ 28 days or 5 half-lives at ICF signature, whichever is longer
  • Having received hormonal therapy within 14 days of enrolment
  • Having received trastuzumab within 21 days of enrolment
  • Prior enrolment in a T-DM1-containing study, regardless of whether the patient received T-DM1 or not
  • History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product.
  • Current peripheral neuropathy of Grade ≥ 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0.3
  • History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those mentioned above.
  • Current unstable ventricular arrhythmia requiring treatment.
  • History of symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] Classes II−IV).
  • History of myocardial infarction or unstable angina within 6 months prior to first study drug administration.
  • Current dyspnoea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy.
  • Current severe, uncontrolled systemic disease other than cancer (e.g., clinically significant pulmonary, hypertension or metabolic disease)
  • Concurrent, serious, uncontrolled infections or current known infection with HIV, active hepatitis B and/or hepatitis C.
  • Major surgical procedure or significant traumatic injury within 28 days before enrolment or anticipation of the need for major surgery during the course of study treatment.
  • Known contraindications for undergoing MRI or CT, including to receive contrast media,

Cohort 1 : additional specific criteria:

• Previous neurosurgery or radiotherapy (radiosurgery, stereotactic radiotherapy, whole brain radiotherapy) to the brain Cohort 2 : no additional specific criteria


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): NCT03203616


Sponsors and Collaborators
Jules Bordet Institute
Investigators
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Study Chair: Evandro de Azambuja, MD Jules Bordet Institute

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Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT03203616    
Other Study ID Numbers: IJB‐BC‐TDM1BM‐2016
First Posted: June 29, 2017    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Trastuzumab
Ado-trastuzumab emtansine
Maytansine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action