E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with ErbB2-positive advanced or metastatic gastric or oesophageal or gsatro-oesophageal junction adenocarcinoma |
Soggetti con adenocarcinoma gastrico o adenocarcinoma dell esofago o della giunzione esofago-gastrica avanzato o metastatico ErbB2 positivi |
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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 | LLT |
E.1.2 | Classification code | 10001150 |
E.1.2 | Term | Adenocarcinoma gastric |
E.1.2 | System Organ Class | 100000004864 |
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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 compare the overall survival (OS) in subjects treated with CapeOx plus lapatinib versus CapeOx plus placebo. |
Confrontare la sopravvivenza globale (Overall Survival - OS) in soggetti trattati con CapeOx piu` lapatinib versus CapeOx piu` placebo |
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E.2.2 | Secondary objectives of the trial |
-To compare the progression free survival (PFS), response rate (RR), and duration of overall response of both treatment arms; -To compare the rate of clinical benefit (as defined by CR+PR+SD) of both treatment arms; -To compare the severity and incidence of qualitative and quantitative toxicities of both treatment arm. |
-Confrontare la sopravvivenza libera da progressione (Progression Free Survival- PFS),il tasso di risposta (RR) e la durata della risposta nei due bracci di trattamento;-Confrontare il tasso di beneficio clinico (definito da CR+PR+SD) nei due bracci di trattamento;-Confrontare la gravita` e l`incidenza delle tossicita` qualitative e quantitative nei due bracci di trattamento. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PHARMACOGENETIC: Vers:00 Date:2007/12/17 Title: Objectives:
LIFE QUALITY: Vers: Date: Title: Objectives:
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FARMACOGENETICA: Vers:00 Data:2007/12/17 Titolo:Pharmacogenetics research Obiettivi:-Relationship between genetic variants and pharmacokinetics of investigational product
-Relationship between genetic variants and safety and/or tolerability of investigatinal product
-Relationship between genetic variants and efficacy of investigational products
QUALITA DELLA VITA: Vers: Data: Titolo:Qaulity of life and medical resource utilisation Obiettivi:
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E.3 | Principal inclusion criteria |
1. Signed informed consent; willing and able to complete all required components of study. 2. Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the esophagus or gastro-esophageal junction. Pathologic confirmation may be made from the metastatic site. Biopsy of the primary tumor is not necessary. Patients with pathologic confirmation from a metastatic site along with clinical/radiological documentation of gastric involvement and no evidence of another primary tumor are also eligible. Allowable histological subtypes include adenocarcinoma NOS, papillary carcinoma, adenocarcinoma, interstitial type, clear cell adenocarcinoma, mucinous carcinoma, signet ring cell carcinoma, undifferentiated carcinoma, carcinoma NOS. 3.Gastric cancer or Esophageal cancer that is unresectable due to locally advanced, metastatic, or locally recurrent. 4. Measurable or non-measurable, but radiologically evaluable disease, according to RECIST. X-rays, scans, or physical exams for either measurable or non-measurable disease must have been completed within 28 days prior to registration. 5. ErbB2 amplification by FISH assessed by the local or designated central laboratory. 6. Age `¥18 years 7. ECOG Performance status `¤ 2. 8. Adequate organ function assessed within 14 days prior randomization. 9. Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. 10. Able to swallow and retain oral medications, and/or receive enteral medications via gastrectomy feeding tube. 11. Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study. 12. Prior/Concurrent Therapy-Surgery as indicate in Protocol pag.32. |
1.Sottoscrizione del consenso informato; soggetti volontari e in grado di completare tutte le procedure richieste dello studio. 2.Adenocarcinoma gastrico o adenocarcinoma dell esofago o della giunzione esofago-gastrica confermato istologicamente. 3. Carcinoma gastrico o Tumore esofageo non resecabile in quanto localmente avanzato, metastatico o localmente ricorrente. 4.Malattia misurabile o non misurabile, ma radiologicamente valutabile secondo RECIST. Radiografie, scansioni o esami obiettivi relativi alla malattia misurabile o non misurabile, devono essere stati eseguiti nei 28 giorni precedenti la registrazione. 5.Amplificazione di ErbB2 mediante FISH secondo la valutazione del laboratorio locale o centrale. 6.Eta` `¥ 18 anni. 7.Performance Status ECOG `¤ 2. 8.Adeguata funzionalita` degli organi valutata nei 14 giorni precedenti la randomizzazione. 9.Frazione di eiezione cardiaca nell intervallo istituzionale di normalita` misurata mediante ecocardiogramma. 10.Soggetto in grado di assumere e trattenere farmaci orali e/o di ricevere farmaci per via enterica mediante tubo di alimentazione per gastrectomia (i soggetti NPO saranno considerati idonei solo dopo verifica del medical monitor dello studio). 11.Donne e uomini potenzialmente fertili devono acconsentire a usare metodi contraccettivi accettabili durante lo studio. 12.Terapia precedente/concomitante come riportato in sinossi pag.16-17. |
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E.4 | Principal exclusion criteria |
1.Pregnant or lactating females at anytime during the study. 2.Known history of active CNS disease. 3.Uncontrolled ascites. 4.Concurrent anti-cancer therapy (chemotherapy, radiation therapy other than for pain relief, immunotherapy, biologic therapy, hormonal therapy or surgery) while taking investigational treatment. 5.Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma. 6.Prior palliative chemotherapy for the treatment of gastric cancer. 7.Prior treatment with oxaliplatin based neoadjuvant or adjuvant chemotherapy completed < 12 months 8.Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease (such as Crohn s disease or ulcerative colitis). 9.Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; ô¸ Myocardial infarction within past 6 months ô¸ New York Association Class III or IV congestive heart failure 10. Pre-existing grade ô 2 motor or sensory neuropathy by CTC v3.0. 11. Uncontrolled infection. 12. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical condition that would interfere with the subject`s safety. 13.Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert`s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment). 14. History of other malignancy except: ô¸ subjects who have been disease-free for 5 years ô¸ subjects with a history of completely resected non-melanoma skin cancer ô¸ subjects with successfully treated in situ carcinoma 15. Unresolved or unstable serious toxicity from prior administration of another investigational drug and/or prior cancer treatment. 16. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. 17. Known history of DPD deficiency. 18. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib, capecitabine, fluorouracil, platins or their excipients. 19. Use of any investigational drug within 30 days prior randomization. 20. Use of concurrent prohibited medications that would interact with study drugs, including herbal remedies and Chinese traditional medicines for cancer, and including any medications or drugs listed in table 1. |
1.Donne in gravidanza o allattamento in qualsiasi stadio dello studio. 2. Storia nota di malattia attiva dell SNC. 3.Ascite incontrollata. 4.Terapia anticancro concomitante (chemioterapia, radioterapia se non per ridurre il dolore, immunoterapia, terapia biologica, terapia ormonale o intervento chirurgico) durante l assunzione del farmaco dello studio. 5. Sarcoma, carcinoide o epidermoide gastrico o carcinoma a cellule squamose. 6. Chemioterapia palliativa precedente per il trattamento del carcinoma gastrico. 7. Trattamento precedente con chemioterapia adiuvante o neoadiuvante a base di oxaliplatino completata da < 12 mesi 8. Sindrome da malassorbimento o malattia gastrointestinale infiammatoria incontrollata (come il morbo di Crohn o la colite ulcerosa). 9. Storia nota di angina incontrollata o sintomatica, aritmia o insufficienza cardiaca congestizia;Infarto del miocardio nei 6 mesi precedenti. Insufficienza cardiaca congestizia di classe III o IV secondo la New York Association 10. Neuropatia motoria o sensoriale preesistente di grado `¥ 2 secondo CTC v3.0. 11. Infezione incontrollata. 12. Una malattia o una condizione concomitante tale da rendere il soggetto inadatto alla partecipazione allo studio o qualsiasi patologia medica grave che interferirebbe con la sicurezza del soggetto. Soggetti con concomitante malattia epatica o biliare attiva (ad eccezione dei pazienti con sindrome di Gilbert, calcoli biliari asintomatici, metastasi epatiche o malattia epatica cronica stabile a giudizio dello sperimentatore). 14. Storia di altra malignita` eccetto: soggetti liberi da malattia per 5 anni, soggetti con storia di tumore cutaneo non melanoma completamente resecato, soggetti con carcinoma in situ trattato con esito positivo. 15.Tossicita` grave irrisolta o instabile da precedente somministrazione di un altro farmaco sperimentale e/o trattamento anticancro. 16. Demenza, stato mentale alterato o altra patologia psichiatrica che impedirebbe la comprensione o l ottenimento del consenso informato. 17. Storia nota di deficienza di DPD. 18. Reazione di ipersensibilita` immediata o ritardata nota o idiosincrasia verso farmaci chimicamente correlati a lapatinib, capecitabina, fluorouracile, platino o rispettivi eccipienti 19. Uso di farmaci sperimentali nei 30 giorni precedenti la randomizzazione. 20. Uso di farmaci concomitanti vietati che interagirebbero con i farmaci dello studio, compresi rimedi erboristici e farmaci tradizionali cinesi contro il cancro, e compresi medicamenti o farmaci elencati nella. Altre considerazioni sui criteri di idoneita` In pazienti che assumevano capecitabina in concomitanza con anticoagulanti derivati della cumarina come warfarin e fenprocumone sono state riferite alterazioni dei parametri di coagulazione e/o emorragia. I soggetti che assumono anticoagulanti a base di cumarina in concomitanza con capecitabina devono essere monitorati regolarmente per evidenziare eventuali alterazioni nei parametri di coagulazione (PT o INR). Gli anziani possono essere piu` sensibili a livello farmacodinamico agli effetti tossici di 5-FU e devono essere monitorati attentamente per evidenziare eventuali effetti avversi della capecitabina. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival (OS), which is defined as the time from randomization until death due to any cause, is the primary endpoint for this study. Progression Free Survival (PFS), which is defined as the time from randomization until date of progression or death due to any cause will be a secondary endpoint of this study. Date of progression will be defined as the date of the first imaging or exam showing disease progression. Response rate and duration of responses are also secondary efficacy endpoints for this study. Please refer to Section 8.3.5.6 (Efficacy Analyses) for additional details. |
La sopravvivenza globale (OS), definita come il tempo tra la randomizzazione e la morte per qualsiasi causa, e` l`endpoint primario dello studio. La data della progressione e` definita come la data del primo test di imaging o esame indicativo di progressione della malattia. La sopravvivenza libera da progressione (PFS), definita come il tempo tra la randomizzazione e la data della progressione o della morte, e` un endpoint secondario dello studio. Tasso di risposta e durata della risposta sono ulteriori endpoint secondari dell`efficacia di questo studio. Si veda il paragrafo per ulteriori dettagli. |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life and medical resource utilisation |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 123 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |