E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
adenocarcinoma of the stomach or the esophagogastric junction (metastatic or not amenable to curative surgery) |
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E.1.1.1 | Medical condition in easily understood language |
adenocarcinoma of the stomach or the esophagogastric junction |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063916 |
E.1.2 | Term | Metastatic gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To test the activity of lapatinib in patients which are HER2 positive by IHC 0/1+/ EFGR+ by FISH or EFGR+ by IHC2/3+. |
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E.2.2 | Secondary objectives of the trial |
1) To explore the activity of lapatinib in the subpopulation which is HER2 negative by FISH, but HER2 positive by IHC (2+ and 3+).
2) To assess the concordance of HER2 determination by FISH and IHC. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
¨ Histologically proven adenocarcinoma of the stomach or the esophagogastric junction, metastatic or not amenable to curative surgery
¨ Availability of tissue material for HER2 and EGFR assessment
¨ Former neoadjuvant/adjuvant chemotherapy allowed if completed ≥ 12 months before inclusion to the study
¨ WHO Performance status 0-1
¨ Age 18 – 75 years
¨ Positive HER2 status by IHC, or positive EGFR by either FISH or IHC at time of randomization
¨ Absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L, hemoglobin > 9 g/dL, and white blood cell count (WBC) > 3 x 109/L within 3 weeks of randomization
¨ Renal function: Serum creatinine ≤ 2.0 mg/dL and Calculated creatinine clearance ≥ 60 ml/min (Cockcroft-Gault method, see appendix E) within 3 weeks of randomization
¨ Clinically normal cardiac function (LVEF ≥Lower Limit of Normal of the insitution and assessed by MUGA or ECHO within 21 days prior to randomization)
¨ All patients (male and female) must use effective contraception methods if of reproducing potential for the whole duration of study and until 1 month after they received the last treatment dose; Females must not be pregnant or breast-feeding at anytime during the study. Women with reproductive potential must have a pregnancy test performed within 3 weeks before randomization.
¨ Ability to swallow and retain oral medication
¨ Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
¨ All indicated timelines and absolute values requested by the eligibility criteria must be adhered to. However, a maximum of +/- 10% of the reference value for laboratory parameters and a maximum of +/- 2 days for timelines may be acceptable. |
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E.4 | Principal exclusion criteria |
¨ Former palliative systemic chemotherapy
¨ Prior exposure to EGFR pathway targeting therapy (antibodies or tyrosine kinase inhibitors)
¨Use of drugs or herbal constituents known to be inducers or inhibitors of CYP3A4 within 30 days prior to initiation of treatment and during treatment with lapatinib
¨ Major hepatic insufficiency (bilirubin ≤ 1.5 x ULN and aspartate aminotransferase
(ASAT)/alanine aminotransferase (ALAT) ≤ 3 x ULN, ≤ 5 x ULN in case of liver metastases) within 3 weeks prior to randomization
¨ Serious cardiac illness in the past 6 months
¨ Clinical signs of CNS involvement
¨ Previous or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin
¨ Other anticancer therapy or other investigational agents while on study
¨ History or evidence of interstitial pneumonitis or pulmonary fibrosis
¨ Uncontrolled infections or serious illnesses, malabsorption syndrome or medical conditions including chronic alcohol abuse, hepatitis, HIV and/or cirrhosis
¨ Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule
¨HER2+ by FISH/HER2+ by IHC2/3+
¨HER2- and EGFR- by FISH and IHC |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this trial is Progression Free Survival (PFS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The disease status and PFS will be regularly assessed every 8 weeks during treatment. Subjects withdrawn from study treatment with SD, PR or CR and no progression will be followed-up
every 3 months for 2 years and every 6 months thereafter. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints are response rate, overall survival and toxicity and
concordance of diagnostic tests |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The disease status and response rate, overall survival and toxicity and
concordance of diagnostic tests will be regularly assessed every 8 weeks during treatment. Subjects withdrawn from study treatment with SD, PR or CR and no progression will be followed-up
every 3 months for 2 years and every 6 months thereafter. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Greece |
Hungary |
Israel |
Poland |
Portugal |
Serbia |
Switzerland |
Turkey |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study occurs when all of the following criteria have been satisfied:
1. 30 days after all patients have stopped protocol treatment
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol: when 77 events will have been observed in the HER2+ IHC0/1+/ EFGR+ by FISH or EFGR+ by IHC2/3+ subgroup, whatever the number of observed events in the other subgroups.
3. The database has been fully cleaned and frozen for this analysis.
|
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |