PHASE I STUDY OF THE COMBINATION OF TRASTUZUMAB EMTANSINE (T-DM1) AND CAPECITABINE IN HER2-POSITIVE METASTATIC BREAST CANCER AND HER2-POSITIVE LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER PATIENTS, FOLLOWED BY A RANDOMIZED, OPEN-LABEL PHASE II STUDY OF TRASTUZUMAB EMTANSINE AND CAPECITABINE VERSUS TRASTUZUMAB EMTANSINE ALONE IN HER2-POSITIVE METASTATIC BREAST CANCER

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-082-14
• Date of registration: 12/05/2015
• Prospective Registration: No
• Primary sponsor: F. HOFFMANN-LA ROCHE LTD.,
• Public title: PHASE I STUDY OF THE COMBINATION OF TRASTUZUMAB EMTANSINE (T-DM1) AND CAPECITABINE IN HER2-POSITIVE METASTATIC BREAST CANCER AND HER2-POSITIVE LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER PATIENTS, FOLLOWED BY A RANDOMIZED, OPEN-LABEL PHASE II STUDY OF TRASTUZUMAB EMTANSINE AND CAPECITABINE VERSUS TRASTUZUMAB EMTANSINE ALONE IN HER2-POSITIVE METASTATIC BREAST CANCER
• Scientific title: PHASE I STUDY OF THE COMBINATION OF TRASTUZUMAB EMTANSINE (T-DM1) AND CAPECITABINE IN HER2-POSITIVE METASTATIC BREAST CANCER AND HER2-POSITIVE LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER PATIENTS, FOLLOWED BY A RANDOMIZED, OPEN-LABEL PHASE II STUDY OF TRASTUZUMAB EMTANSINE AND CAPECITABINE VERSUS TRASTUZUMAB EMTANSINE ALONE IN HER2-POSITIVE METASTATIC BREAST CANCER
• Date of first enrolment: 01/06/2014
• Target sample size: 8
• Recruitment status: Pending
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=082-14
• Study type: Interventional
• Study design: Phase II will be conducted in mBC patients only. This part of the study will explore the efficacy and safety of the combination treatment of trastuzumab emtansine (T-DM1) and capecitabine, at 700 mg/m2 bid (the recommended MTD), compared with trastuzumab emtansine alone in patients with mBC.; Approximately 210 additional patients with HER2-positive mBC will be randomized into the Phase II part of the study. Patients in the Phase I part of the study will not contribute to the Phase II part of the study; however, they will be followed up until end of study (EOS).
• Phase: II

Countries of recruitment

Argentina, Brazil, Canada, France, Germany, Greece, Italy, Liberia, Portugal, Russian Federation, Serbia, Slovakia, Spain

Contacts

• Name: Roberto Navarro Carrasco
• Affiliation: PRODUCTOS ROCHE Q.F.S.A.

• Name: Roberto Navarro Carrasco
• Affiliation: PRODUCTOS ROCHE Q.F.S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female.
2. Age ≥ 18 years old.
3. Signed informed consent before any study-specific procedure.
4. Able and willing to comply with the protocol.
5. Negative serum pregnancy test for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal ( ≥ 12 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in the medical history confirming that the patient is not of childbearing potential.
6. For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception and to continue its use for the duration of study treatment and for 7 months after the last dose of study treatment (see Section 5.2.4 in the protocol).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
8. Blood:
a) Platelet count > 100,000 cells/mm3
b) International normalized ratio (INR) < 1.5
c) Absolute neutrophil count (ANC) > 1,500 cells/mm3
d) Hemoglobin > 9.0 g/dL. Patients are allowed to have received transfusion to achieve this level.
9. Liver function:
a) Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or direct bilirubin ≤ 1.5 × ULN in patients with documented Gilbert’s syndrome.
b) Serum glutamic oxaloacetic transaminase (SGOT)/aspartate transaminase (AST) and serum glutamic pyruvic transaminase (SGPT)/alanine transaminase (ALT) ≤ 2.5 × ULN.
c) Alkaline phosphatase ≤ 2.5 × ULN. In patients with bone metastases: alkaline phosphatase ≤ 5 × ULN.
d) Evidence of stable liver function during the month prior to enrollment with liver function test (LFT) fluctuations not exceeding 2.5 × ULN (for AST, ALT) and 1.5 × ULN (for total bilirubin).
10. Renal function:
a) Serum creatinine of < 177 μmol/L or calculated creatinine clearance (CL) > 50 mL/min. If urine dipstick for proteinuria is ≥ 2+ at baseline, the patient must undergo 24-hour urine collection and demonstrate ≤ 1 g of protein/24 hours.
11. Cardiac function:
a) Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
12. Life expectancy ≥12 weeks
13. Histologically or cytologically confirmed breast cancer.
14. HER2-positive disease, defined as IHC 3+ or ISH positive.
15. Tumor block or 8 slides available for retrospective central confirmation of HER2-positivity (central confirmation not necessary for enrollment).
16. mBC with at least one measurable lesion according to RECIST v.1.1.
17. Disease progression on at least one prior regimen containing trastuzumab and chemotherapy either separately or in combination.
18. Patients must have recovered from previous treatments

Exclusion criteria:
1. Prior treatments before first study treatment:
a) Investigational therapy within ≤ 28 days or five half-lives, whichever is longer.
b) Hormonal therapy within 14 days.
c) Trastuzumab within 21 days.
2. Prior enrollment in a trastuzumab emtansine-containing study, regardless of whether the patient received trastuzumab emtansine.
3. Prior treatment with capecitabine.
4. History of severe or unexpected reactions to fluoropyrimidine or known hypersensitivity to fluorouracil.
5. Related capecitabine contraindications:
a) Treatment with sorivudine or its chemically-related analogs, such as brivudine.
b) Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
c) Signs or symptoms suggesting that the patient has dihydropyrimidine dehydrogenase (DPD) deficiency.
6. History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product.
7. History of exposure to the following cumulative doses of anthracyclines:
a) Doxorubicin or liposomal doxorubicin > 500 mg/m2.
b) Epirubicin > 900 mg/m2.
c) Mitoxantrone > 120 mg/m2
d) If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
8. Brain metastases that are symptomatic, or require any radiation, surgery, or steroid therapy to control symptoms within 28 days before first study drug administration.
9. Current peripheral neuropathy of Grade ≥ 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0.
10. 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.
11. Current unstable ventricular arrhythmia requiring treatment.
12. History of symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] Classes II−IV).
13. History of myocardial infarction or unstable angina within 6 months prior to first study drug administration.
14. History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab treatment.


Age minimum: 18
Age maximum: 80
Gender: --

Health Condition(s) or Problem(s) studied

C50

-C50 Malignant neoplasm of breast
Malignant neoplasm of breast

Malignant neoplasm of breast

Intervention(s)

Exploration of efficacy and safety in mBC will be based on approximately 210 randomized patients in total.

Source(s) of Monetary Support

Industria Farmaceutica

Ethics review

Status: Approved
Approval date: 27/11/2014
Contact:

[e-mail]

Comite Institucional de Etica en Investigacion de la Asociacion Benefica Prisma

616-5500 Anx. 246

[e-mail]