Patients With Brain Metastases From HER2-positive Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02135159
• Date of registration: 06/02/2014
• Prospective Registration: No
• Primary sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Public title: Patients With Brain Metastases From HER2-positive Breast Cancer BIRTH
• Scientific 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
• Date of first enrolment: February 2014
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02135159
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

France

Contacts

• Name: David AZRIA
• Affiliation: ICM

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HER2-positive Breast Cancer

Intervention(s)

Drug: TDM1

Radiation: Brain Sequential RT

Primary Outcome(s)

optimal sequences of combined treatment [Time Frame: 3 months]

Secondary Outcome(s)

objective response [Time Frame: 1 year]

Secondary ID(s)

VA2012/38

Source(s) of Monetary Support

Please refer to primary and secondary sponsors