Download Inclusion/exclusion criteria

Indication
Estomac et junction oeso-gastrique, métastatique
Title
A double-blind, placebo-controlled, randomized, multicenter Phase III
Study evaluating the efficacy and safety of pertuzumab in combination with
trastuzumab and chemotherapy in patients with HER2 -positive metastatic
gastroesophageal junction and gastric cancer .
Protocol ID
Jacob BO25114 study
Phase
Phase III
Sponsor
F. Hoffmann-La Roche Ltd.
Local Principal
Investigator
Dr Dorothea Wagner
Primary Objective
To compare overall survival (OS) in patients treated with pertuzumab in
addition to trastuzumab (Herceptin®) plus fluoropyrimidine plus cisplatin
(TFP) versus patients treated with placebo in addition to TFP
Inclusion/exclusion Main Inclusion Criteria include the following
criteria
• Age≥ 18 years
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Signed Informed Consent document
Histologically confirmed (by enrolling center) metastatic
adenocarcinoma of the stomach or GEJ
HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter
in combination with ISH+, as assessed by a sponsor-designated
central laboratory on a primary or metastatic tumor
Availability of formalin-fixed paraffin-embedded representative
tumor tissue for central confirmation of HER2 is mandatory.
Measurable or evaluable non-measurable disease as assessed by
the investigator, according to Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1
Eastern Cooperative Oncology Group (ECOG) performance status
0 or 1
Main Exclusion Criteria include the following:
Cancer Related Criteria
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Previous systemic cytotoxic chemotherapy for advanced
(metastatic) disease
History of exposure to the following cumulative doses of
anthracyclines:
o Epirubicin > 720 mg/m2
o Doxorubicin or liposomal doxorubicin > 360 mg/m2
o Mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2
o Other (e.g., liposomal doxorubicin or other anthracycline
greater than the equivalent of 360 mg/m2 of doxorubicin)
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o If more than one anthracycline has been used, then the
cumulative dose must not exceed the equivalent of 360
mg/m2 of doxorubicin.
Evidence of disease progression documented within 6 months after
completion of prior neoadjuvant or adjuvant cytotoxic
chemotherapy, or both, or radiotherapy for gastric or GEJ
adenocarcinoma
Previous treatment with any HER2-directed therapy, at any time, for
any duration
Previous exposure to any investigational treatment within 30 days
before the first dose of study treatment
Radiotherapy within 30 days before the first dose of study treatment
(within 2 weeks if given as palliation to peripheral bone metastases,
if recovered from all toxicities)
History or evidence of brain metastasis
Clinically significant active GI bleeding
Residual toxicity resulting from previous therapy (e.g., hematologic,
cardiovascular, or neurologic toxicity that is Grade ≥ 2). Alopecia is
permitted.
Other malignancy (in addition to GC) occurring within 5 years before
enrollment, except for carcinoma in situ of the uterine cervix or
squamous or basal cell carcinoma of the skin that has been
previously treated with curative intent
General Exclusion Criteria
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Documented history of congestive heart failure of any New York
Heart Association (NYHA) criteria
Angina pectoris requiring treatment
Myocardial infarction within the past 6 months before the first dose
of study treatment
Clinically significant valvular heart disease or uncontrollable highrisk cardiac arrhythmia (i.e. atrial tachycardia with a heart rate
>100/min at rest), significant ventricular arrhythmia (ventricular
tachycardia) or higher-grade atrioventricular-block (second degree
AV-block Type 2 [Mobitz 2] or third degree AV-block)
History or evidence of poorly controlled arterial hypertension
(systolic blood pressure > 180 mmHg or diastolic blood pressure
>100 mmHg)
Baseline left ventricular ejection fraction (LVEF) value< 55%
Dyspnea at rest due to complications of advanced malignancy or
other disease or requirement of supportive oxygen therapy
Any significant uncontrolled intercurrent systemic illness (e.g.,
active infection, poorly controlled diabetes mellitus)
Previous major surgery within 30 days before the first dose of study
treatment, unless completely recovered
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Known infection with HIV, hepatitis B virus, or hepatitis C virus that
requires active treatment
Ongoing chronic treatment or high-dose treatment with
corticosteroids. Inhaled steroids and clinically indicated short
courses of oral steroids are permitted.
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Known hypersensitivity to any component of study treatment
Current use of antiviral drug sorivudine or its chemically related
analogs, such as brivudine
Lactating female patient
Any patient unwilling or unable to use adequate contraceptive
measures during study treatment and for at least 6 months after the
last dose of pertuzumab or trastuzumab, except for a patient with
documented surgical sterilization or a postmenopausal female