The Innovation trial: Trastuzumab with or without Pertuzumab as perioperative chemotherapy for Her-2 positive stomach cancer
- Conditions
- HER-2 positive, resectable gastric cancerMedDRA version: 23.0Level: PTClassification code 10066896Term: HER2 positive gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-000722-38-IT
- Lead Sponsor
- EORTC AISBL/IVZW
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 225
Registration
Assessment of the HER-2 status of all potentially eligible patients in the central lab OR Assessment of the HER-2 status by IHC in the local lab and mandatory confirmation of the HER-2 positive result in the central lab.
If a European site selects option a) FFPE blocks or 20x 3-5 11m unstained paraffin sections from all potentially eligible patients must be sent for central assessment of the HER-2 status. If a European site selects option b) and performs local assessment of the HER-2 status by IHC, FFPE blocks or 20x3-5 11m unstained paraffin sections from patients with HER-2 IHC status 1+, 2+ or 3+ must be sent for confirmation to the central lab.
• All patients (HER-2 positive and negative) should be registered in the trial as soon as possible after signing PISIC.
• Histologically proven, gastric or GE-junction adenocarcinoma
• Absence of distant metastases on CT scan of thorax and abdomen
+ Patient medically fit for gastrectomy/oesophagectomy
+ Age ~ 18 years
• WHO performance status 0 - 1
+ HER2 status
• For European patients if site chooses option (b): Availability of local HER-2 IHC test results
• Availability of the paraffin block
HER-2 assessmenVconfirmation.
Randomization
+ HER-2 overexpression, as determined by central testing using immunohistochemistry (IHC 3+) or the combination of IHC 2+ and HER- 2 FISH positive (please see pathology guidelines).
+ Amenable to gastrectomy/oesophagectomy with curative intent as confirmed by a multidisciplinary team discussion
+ UICC tumor stage lb to Ill, as defined by CT.
• The cardiac ejection fraction (LVEF), as determined by echocardiography, MUGA or cardiac MRI should be at least 55% (assessed within 14 days prior to randomization).
• Adequate organ function (assessed within 7 days prior to randomization):
• White blood cell count (WBC) > 3 x 109/L
• Absolute neutrophil count (ANC) > 1.5 x 109/L
• Platelets ~ 100 x 109/L
• Hemoglobin ~ 9 g/dl
• Estimated glomerular filtration rate (eGFR) according to MDRD (see
Appendix G) should be > 60 ml/min
• Total bilirubin within normal limits (if the patient has documented Gilbert's disease s 1.5 x ULN or direct bilirubin s ULN)
+Aspartate transaminase (AST) and alanine transaminase (ALT) s 2.5 x ULN
+ Absence of any psychological. familial. sociological or geographical
condition potent ially hampering compliance with the study protocol and
follow-up schedule; those conditions should be discussed with the patient before registration in the trial
+ For women who are not postmenopausal (> 12 months of nontherapy induced amenorrhea} or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or
combined contraceptive methods that result in a failure rate of< 1% per year during the treatment period and for at least 7
months after the last treatment dose
• For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a
failure rate of
< 1% per year during the treatment period and for at least 7 months after the last dose of study treatment. Abstinence is only
acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g. calendar. ovulation. symptothermal. or postovulation
methods) and withdrawal are not acceptable methods for contraception .
+ For all female patients who are not confirmed post menopausal (> 12months of non-t herapy induced amenorrhea) or surgically
sterile (absence of ovaries a
prior chemo- or antibody therapy
• history of significant cardiac disease defined as:
• Symptomatic CHF (NYHA classes 11-IV, see Appendix D)
• High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a
heart rate > 100/min at rest, significant ventricular arrhythmia
(ventricular tachycardia) or higher-grade AV-block (second degree AVblock
Type 2 [Mobitz 21 or third degree AV-block)
• History of myocardial infarction within 6 months prior to randomization
• Clinically significant valvular heart disease
• Angina pectoris requiring anti-anginal treatment
• current uncontrolled hypertension (persistent systolic> 180 mmHg
and/or diastolic > 100 mmHg)
•known hypersensitivity to the components of trastuzumab,
pertuzumab, cisplatin, 5-FU or capecitabine
• known dihydropyrimidine dehydrogenase (DPD) deficiency
• ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine
• chronic treatment with high-dose intravenous corticosteroids
• Investigator and patient have to agree to replace any oral anticoagulations by subcutaneous administration of low-molecular
weight heparin (LMWH) in equivalent doses before treatment start, or if on oral anticoagulations and unwilling to switch to LMWH,
patients have to be treated with mandatory 5-FU i.v. instead of capecitabine.
• previous malignancy within the last 5 years, with the exception of adequately treated cervical carcinoma in situ, localized nonmelanoma
skin cancer, or other curatively treated cancer without impact on the patient's overall prognosis according to the
judgment of the investigator.
Female patients should not be breast feeding.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To increase the major pathological response rate<br>(< 10% vital tumor cells) to neoadjuvant treatment by integrating both trastuzumab and pertuzumab into perioperative chemotherapy for HER-2 positive. resectable gastric cancer.;Secondary Objective: N/A;Primary end point(s): The primary endpoint of the phase II study<br>is the major pathological response rate(< 10% vital tumor cells).;Timepoint(s) of evaluation of this end point: Post surgery.<br>The analysis of the primary endpoint will occur:<br>1. 30 days after all patients have undergone surgery<br>2. the trial is mature for the analysis of the primary endpoint as defined<br>in the protocol<br>3. the database has been fully cleaned and frozen for the analysis
- Secondary Outcome Measures
Name Time Method