HER2-positive adenocarcinoma of the stomach or gastroesophageal junction MedDRA version: 14.0 Level: LLT Classification code 10066896 Term: HER-2 positive gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease-Specific Inclusion Criteria • Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction with inoperable locally advanced or metastatic disease, not amenable to curative therapy. Patients with advanced disease who present with a recurrence post operatively (when intent of surgery was cure) are also eligible for entry. • Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1, assessed using imaging techniques (CT or MRI), or non-measurable disease that can be followed • HER2 positive tumor defined as either IHC 3+ or IHC 2+ in combination with ISH +, as assessed by central laboratory on primary or metastatic tumor ISH positivity is defined as a ratio of >= 2.0 for the number of HER2 gene copies to the number of signals for CEP17. Availability of formalin-fixed paraffin-embedded (FFPE) tissue with at least 5 mm of invasive tumor for central confirmation of HER2 eligibility is mandatory. • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 • Baseline LVEF >= 55% (measured by ECHO or MUGA) • Life expectancy of at least 3 months. General Inclusion Criteria • Male or female • Age >= 18 years • Signed informed consent • For women of childbearing potential and male participants with partners of childbearing potential: agreement to use a highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner (see Section 7.2.6 for details). Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study medication. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: Cancer-Related Exclusion Criteria • Previous chemotherapy for advanced or metastatic disease, except that prior adjuvant or neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant or neoadjuvant therapy and enrollment in the study. Adjuvant or neoadjuvant treatment with platinum-based therapy is not allowed. • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (e.g., patients with partial or total gastrectomy can enter the study, but not those with a jejunostomy probe) • Active (significant or uncontrolled) gastrointestinal bleeding • Residual relevant toxicity resulting from previous therapy (e.g., neurological toxicity of >= Grade >= 2 [NCI CTCAE]), with the exception of alopecia • Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma. Exclusion Criteria Related to Hematological, Biochemical, and Organ Function • Any of the following abnormal laboratory tests immediately prior to randomization: Serum total bilirubin > 1.5 times the upper limit of normal (ULN) or, for patients with known Gilberts syndrome, serum total bilirubin > 2 × ULN For patients with no liver and no bone metastases: AST or ALT > 2.5 × ULN, and alkaline phosphatase (ALP) > 2.5 × ULN In patients with liver metastases and no bone metastases: AST or ALT > 5 × ULN, and ALP > 2.5 × ULN In patients with liver metastases and bone metastases: AST or ALT > 5 × ULN, and ALP > 10 × ULN; In patients with bone metastases and no liver metastases: AST or ALT > 2.5 × ULN, and ALP > 10 × ULN Albumin = 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV block (second-degree AV block Type 2 [Mobitz II] or third-degree AV block) Angina pectoris requiring anti-anginal medication Clinically significant valvular heart disease Evidence of transmural infarction on ECG Poorly controlled hypertension (e.g., systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg) • Dyspnea at rest due to complications of advanced malignancy or other disease, or requirement for supportive oxygen therapy • Treatment with chronic or high-dose corticosteroid therapy. Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed. • Clinically significant hearing abnormality • Known dihydropyrimidine dehydrogenase deficiency. General Exclusion Criteria • History or clinical evidence of brain metastases • Serious uncontrolled systemic intercurrent illness (e.g., infections or poorly controlled diabetes) • Pregnant or lactating. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization, irrespective of the method of contraception used. • Radiotherapy within 4 weeks prior to start of study treatment, or within 2 weeks prior to start of study treatment if palliative radiotherapy is given to bone metastatic site peripherally and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To estimate the minimum (trough) pertuzumab concentration (Cmin) at Day 43 for two dose levels of pertuzumab in order to identify a dose that produces a steady-state Cmin of = 20 µg/mL in 90% of patients receiving pertuzumab and trastuzumab plus chemotherapy as first-line treatment for HER2-positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or gastroesophageal junction • To evaluate the safety and tolerability of two dose levels of pertuzumab in combination with trastuzumab and chemotherapy administered every 3 weeks to patients with HER2-positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or gastroesophageal junction;Secondary Objective: To make an exploratory assessment of the anti-tumor activity of pertuzumab in combination with trastuzumab and chemotherapy in patients with HER2 positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or gastroesophageal junction;Primary end point(s): Minimum (trough) serum concentration (Cmin) for pertuzumab;Timepoint(s) of evaluation of this end point: Day 43 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): This study is not designed or powered to provide an accurate evaluation of efficacy. Thus, efficacy analyses are exploratory and no comparisons between dose levels will be made. Investigator-assessed tumor response will be used to summarize best overall response at the end of Cycles 3 and 6 for each treatment arm, defined as patients with a complete or partial response as determined by RECIST.;Timepoint(s) of evaluation of this end point: End of cyles 3 and 6 | — |
Countries
Belgium, Czech Republic, European Union, Germany, Italy, Korea, Republic of, Netherlands, Spain
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed