A study in HER2-positive breast cancer that has spread to other organs or tissues and has not responded to a course of anti-cancer treatment and a study in HER2-positive inoperable gastric cancer or gastric cancer that has spread to other organs or tissues.
- Conditions
- HER2-positive metastatic breast cancer and HER2-positive locally advanced or metastatic gastric cancer.MedDRA version: 19.0Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: PTClassification code 10066896Term: HER-2 positive gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001547-46-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
For mBC Patients:
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 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 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)
7.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 × 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 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)LVEF = 50% by echocardiogram (ECHO) or multiple-gated acquisition (scan) (MUGA)
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.Metastatic breast cancer (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.
Patients may be eligible to receive study therapy in the first-line setting if trastuzumab and chemotherapy were given in the [neo] adjuvant setting.
18.Patients must have recovered from previous treatments
For mGC Patients: Inclusion criteria 1-12 same as mBC.
13.Histologically or cytologically confirmed mGC or locally advanced gastric cancer.
14.HER2 positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ or IHC 2+ and ISH+, prospectively confirmed by a Sponsor-designated central laboratory prior to enrollment. ISH positivity is defined as a ratio of = 2.0 for the number of HER2 gene copies to the number of signals for CEP17.
a)Archival tumor samples obtained from primary or metastatic sites are
For mBC Patients:
1. Prior treatments before first study treatment
a)Investigational therapy within = 28 days or 5 half-lives, whichever is longest
b)Hormonal therapy within 14 days
c)Trastuzumab within 21 days
2.Prior treatment with trastuzumab emtansine or prior enrollment in a trastuzumab emtansine-containing study, regardless of whether the patient received prior 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 analogues, such as brivudine
b)Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
c)Known complete absence of dihydropyrimidine dehydrogenase activity
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 NCI CTCAE, v4.0
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 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
15.Severe dyspnea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy
16.Clinically significant malabsorption syndrome or inability to take oral medication
17.Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
18.Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment
19.Current pregnancy or lactation
20.Current known active infection with HIV, HBV, and/or HCV
a)For patients who are known carriers of HBV, active hepatitis B infection must be ruled out based on negative serologic testing and/or determination of HBV DNA viral load per local guidelines
21.Lapatinib = 14 days before first study drug administration
22.Previous radiotherapy for the treatment of mBC is not allowed if:
a)The last fraction of radiotherapy has been administered within 14 days prior to first study drug administration (28 days for patients with radiotherapy to control symptoms of brain metastases, see exclusion criterion 8).
b)More than 25% of marrow-bearing bone has been irradiated.
c)Any acute toxicity has not resolved to Grade = 1 before first study drug administration.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method