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Patients With Brain Metastases From HER2-positive Breast Cancer (BIRTH)

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ClinicalTrials.gov Identifier: NCT02135159
Recruitment Status : Completed
First Posted : May 9, 2014
Last Update Posted : August 14, 2017
Sponsor:
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary:
The purpose of this study is to determine the optimal sequences of combined trastuzumab emtansine (T-DM1) and whole-brain radiotherapy in patients presenting brain metastases from HER2-positive breast cancer in terms of acute toxicities and blood/cerebrospinal fluid T-DM1 pharmacokinetics.

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer Drug: TDM1 Radiation: Brain Sequential RT Phase 1

Detailed Description:
Determine the best sequences.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Feasibility of Different Sequences of Combined Trastuzumab Emtansine (T-DM1) and Whole-brain Radiotherapy in Patients With Brain Metastases From HER2-positive Breast Cancer
Study Start Date : February 2014
Actual Primary Completion Date : February 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: TDM1 concommitant with RT
T-DM1 (First injection day 1) followed by brain sequential RT (start day D3), second injection T-DM1 day 22.
Drug: TDM1
administration of the TDM1 by IV perfusion
Other Name: no other names

Radiation: Brain Sequential RT
local RT
Other Name: No other names

Experimental: TDM1 during and after RT
Brain sequential RT (start day 1) followed by T-DM1 (First injection day 15), second injection T-DM1 day 36.
Drug: TDM1
administration of the TDM1 by IV perfusion
Other Name: no other names

Radiation: Brain Sequential RT
local RT
Other Name: No other names

Experimental: RT before TDM1
Brain sequential RT (start day 1) followed by T-DM1 (First injection day 22), second injection T-DM1 day 43.
Drug: TDM1
administration of the TDM1 by IV perfusion
Other Name: no other names

Radiation: Brain Sequential RT
local RT
Other Name: No other names

Experimental: TDM1 before RT
T-DM1 (First injection day 1) followed by brain sequential and concomitant RT (start day D18), second injection T-DM1 day 22.
Drug: TDM1
administration of the TDM1 by IV perfusion
Other Name: no other names

Radiation: Brain Sequential RT
local RT
Other Name: No other names




Primary Outcome Measures :
  1. optimal sequences of combined treatment [ Time Frame: 3 months ]
    To determine the optimal sequences of combined trastuzumab emtansine (T-DM1) and whole-brain radiotherapy in patients presenting brain metastases from HER2-positive breast cancer in terms of acute toxicities and blood/cerebrospinal fluid T-DM1 pharmacokinetics.


Secondary Outcome Measures :
  1. objective response [ Time Frame: 1 year ]
    Objective responses (complete and partial response) by MRI according to the RECIST criteria (v1.1) and volumetric assessment



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

Inclusion Criteria:

  1. Histologically confirmed invasive breast cancer with stage IV disease.
  2. HER-2 positive primary tumor, defined as: IHC3+, or IHC2+ and ISH positive.
  3. Non operable brain metastases (n ≥ 2) with at least one measurable CNS lesion ≥ 10 mm on T1-weighted gadolinium-enhanced MRI.
  4. No stereotaxie radiotherapy indication
  5. At least two weeks from any specific breast cancer treatment (such as Trastuzumab, chemotherapy, immunotherapy/biological response modifiers, endocrine therapy and radiotherapy).
  6. Adequate hematologic function (ANC ≥1x109/L, platelets ≥100 000/L; Hb >10g/dL), renal function (creatinine ≤ 1.5x UNL) and hepatic function (albumin ≥2.5 g/dL; serum bilirubin ≤1.5x ULN unless due to Gilbert's syndrome; AST and ALT ≤ 5x ULN if documented liver metastasis or ≤ 3x ULN without liver metastasis).
  7. At least 18 years old.
  8. ECOG Performance Status of 0 to 2.
  9. Life expectancy ≥ 3 months.
  10. Potentially reproductive patients must agree to use an effective contraceptive method while on treatment, beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product for women. Males able to father a child must practice adequate methods of birth control or practice complete abstinence from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment.
  11. Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and/or urine pregnancy test 48 hours prior to the administration of the first study treatment.
  12. Patients must be affiliated to a Social Security System.
  13. Patient information and written informed consent form signed.

Exclusion Criteria:

  1. Previous whole brain radiotherapy (WBRT) or brain stereotaxie radiotherapy.
  2. Planned or concurrent systemic treatment or radiation therapy (other than corticosteroid, bisphosphonates or mannitol).
  3. Known contra-indication to MRI.
  4. Active concurrent malignancy. If there is a history of prior malignancy, the patient must be disease free for at least 10 years.
  5. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as :

    • infection,
    • cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, LVEF ≤ 50%,
    • current active hepatic or renal disease
  6. Pregnant women, women who are likely to become pregnant or are breast-feeding.
  7. Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  8. Known hypersensibility to any component of T-DM1
  9. Patients who received any other investigational drugs within the 30 days prior to the screening visit.
  10. Individual deprived of liberty or placed under the authority of a tutor.
  11. Leptomeningeal metastases diagnosed by MRI
  12. Inclusion in another protocol within 30 days
  13. Brain metastases with severe intracranial hypertension clinical signs
  14. Other cancer except the known primary tumor or in situ cervix cancer or basocellular carcinoma

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): NCT02135159


Locations
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France
Institut regional du Cancer - Val d Aurelle
Montpellier, France, 34298
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Investigators
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Principal Investigator: David AZRIA ICM Co. Ltd.
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Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier: NCT02135159    
Other Study ID Numbers: VA2012/38
First Posted: May 9, 2014    Key Record Dates
Last Update Posted: August 14, 2017
Last Verified: August 2017
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases