HER2-positive advanced gastroesophageal junction/gastric cancer MedDRA version: 14.1 Level: LLT Classification code 10066896 Term: HER-2 positive gastric cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pertuzumab (rhuMAb 2C4)
Product Code: Ro 436-8451/F01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PERTUZUMAB
CAS Number: 380610-27-5
Other descriptive
rhuMAb HER2, Anti-HER
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease-Specific Inclusion Criteria 1. Histologically confirmed (by enrolling center) metastatic adenocarcinoma of the stomach or GEJ 2. 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 Note: ISH positivity is defined as a ratio of ? 2.0 for the number of HER2 gene copies to the number of signals for chromosome 17 centromere (CEP17). For IHC scoring, the cutoffs as approved by the Food and Drug Administration (FDA) in the context of ToGA apply. Availability of formalin-fixed paraffin-embedded (FFPE) representative tumor tissue for central confirmation of HER2 is mandatory. (See Section 4.5.1.1 for further details.) 3. Measurable or evaluable non-measurable disease as assessed by the investigator, according to RECIST v1.1; see Appendix 3. 4. Eastern Cooperative Oncology Group (ECOG) PS 0 or 1 5. Life expectancy ? 3 months General Inclusion Criteria 6. Age? 18 years 7. Ability to comply with requirements of the protocol, as assessed by the investigator 8. Signed Informed Consent document 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 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 280
Exclusion criteria
Exclusion criteria: Cancer-Related Exclusion Criteria 1. Previous systemic cytotoxic chemotherapy for advanced (metastatic) disease 2. History of exposure to the following cumulative doses of anthracyclines: a. Epirubicin > 720 mg/m2 b. Doxorubicin or liposomal doxorubicin > 360 mg/m2 c. Mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2 d. Other (e.g., liposomal doxorubicin or other anthracycline greater than the equivalent of 360 mg/m2 of doxorubicin) e. If more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin. 3. 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 4. Previous treatment with any HER2-directed therapy, at any time, for any duration 5. Previous exposure to any investigational treatment within 30 days before the first dose of study treatment 6. 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) 7. History or evidence of brain metastasis 8. Clinically significant active GI bleeding (Grade ? 2 according to NCI CTCAE v4.03) 9. Residual toxicity resulting from previous therapy (e.g., hematologic, cardiovascular, or neurologic toxicity that is Grade ? 2). Alopecia is permitted. 10. 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 Clinical Laboratory Exclusion Criteria (must be confirmed within 7 days before first dose of study treatment) 11. Absolute neutrophil count (ANC) 1.5 × upper limit of normal (ULN) of laboratory normal range; in case of known Gilbert disease a total bilirubin of up to 2 × ULN is permitted. 16. AST, ALT, and alkaline phosphatase (ALP) parameters: a) In patients with no liver and no bone metastases i. AST or ALT > 1.5 × ULN, and ALP > 2.5 ×ULN ii. AST or ALT > 2.5 ×ULN b) In patients with liver metastases and no bone metastases i. AST or ALT > 5 × ULN, and ALP > 2.5 ×ULN c) In patients with liver metastases and bone metastases i. AST or ALT > 5 × ULN, and ALP > 10×ULN d) In patients with bone metastases and no liver metastases i. AST or ALT > 1.5 × ULN, and ALP > 10 ×ULN 17. Serum albumin 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) 23. History or evidence of poorly controlled arterial hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure >100 mmHg) 24. Baseline LVEF v
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare overall survival (OS) in patients treated with pertuzumab in addition to Herceptin® (trastuzumab) plus fluoropyrimidine plus cisplatin (TFP) versus patients treated with placebo in addition to TFP;Secondary Objective: ? To compare investigator-assessed PFS, ORR, duration of objective response (DoR), and clinical benefit rate (CBR) between the two treatment arms ? To compare the safety profile between the two treatment arms ? To assess the pharmacokinetics of pertuzumab ? To compare the patient-reported outcomes (PROs) of health-related quality of life (HRQoL), GC, and treatment-related symptoms as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 scale and its GC module, the QLQ-STO22, for patients in each treatment arm;Primary end point(s): The primary efficacy variable, OS, is the time from the date of randomization to the date of death from any cause. For patients who are still alive on the date of clinical data cutoff for the OS analysis, the last date when the patient is known to be alive on or prior to the clinical cut-off date will be used to determine the censoring date. Patients who do not have any postbaseline data (e.g., dosing records, imaging dates, visit dates) will be censored at the date of randomization plus 1 day.;Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed approx. 50 months after FPI when 502 deaths will have occurred ? which is expected to happen in approx. JUL2017. However, if the interim efficacy analysis (351 deaths) provided significant and meaningful treatment benefit and an acceptable safety profile can be seen, then the study could be stopped early. The interim analysis is expected to take place in approx. AUG2016 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Investigator-assessed progression-free survival (PFS), objective response rate (ORR), duration of objective response (DoR), and clinical benefit rate (CBR).;Timepoint(s) of evaluation of this end point: These will be analysed together with the primary endpoint. | — |
Countries
Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, China, Croatia, El Salvador, European Union, Finland, Germany, Guatemala, Hong Kong, Hungary, India, Italy, Japan, Kazakhstan, Korea, Republic of, Macedonia, the former Yugoslav Republic of, Malaysia, Mexico, Netherlands, Panama, Peru, Poland, Russian Federation, Serbia, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed