| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Phase II: Patients with pancreatic cancer. |
| Fase II: Pazienti con carcinoma pancreatico. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Phase II: Patients with pancreatic cancer who can not be cured by surgery or drug. |
| Fase II: Pazienti con carcinoma pancreatico che non possono essere curati con chirurgia o farmaci |
|
| 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 | 10051971 |
| E.1.2 | Term | Pancreatic adenocarcinoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
| Phase 2; Primary objective is to determine if overall survival in patients with Stage II-IV unresectable pancreatic cancer administered LY2603618 plus gemcitabine exceeds gemcitabine monotherapy |
| L’obiettivo primario della Fase II dello studio è determinare se la sopravvivenza complessiva (OS) dei pazienti con carcinoma pancreatico non resecabile allo stadio II-IV in terapia di associazione con LY2603618 e gemcitabina risulti superiore rispetto all’OS dei pazienti in monoterapia con gemcitabina. |
|
| E.2.2 | Secondary objectives of the trial |
| Phase II: To characterize further the safety and toxicity profile of LY2603618 when administered after gemcitabine and to compare it to the safety profile of gemcitabine monotherapy, stimate other time-to-event variables, explore the percentage change in tumor size at 8 weeks, document response rate per RECIST, evaluate the PKs of gemcitabine, dFdU and LY2603618 in combination, assess biomarker responses associated with LY2603618 and gemcitabine combination, perform an exploratory assessment of QTc. |
| • Caratterizzare ulteriormente il profilo di sicurezza e tossicità di LY2603618 somministrato dopo gemcitabina e confrontarlo con il profilo di sicurezza di gemcitabina in monoterapia nella popolazione con carcinoma pancreatico in fase avanzata, Stimare altre variabili di tempo all’evento, Analizzare la variazione percentuale delle dimensioni della massa tumorale a 8 settimane, Documentare il tasso di risposta in base ai criteri RECIST, Determinare la farmacocinetica di gemcitabina, deossidifluorouridina (dFdU) e LY2603618 in associazione, Eseguire una valutazione esplorativa dell’intervallo QTc |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| [2] Phase 2 portion: Histological or cytological diagnosis of adenocarcinoma of the pancreas that is locally advanced (Stage II, III) or metastatic (Stage IV) and not amenable to resection with curative intent. [3] For Phase 2 only: Have measurable disease or non-measurable disease, defined according to RECIST [4] Males or females at least 18 years of age [5] Have given written informed consent prior to any study-specific procedures. [6] Have adequate organ function(hematologic, hepatic, renal) [7] Have a performance status of ≤2 on the ECOG scale [8] For Phase 1: Patients enrolling in Phase 1 portion of study may have prior chemotherapy, radiotherapy, cancer-related hormone therapy, or other investigational therapy as treatment. There is no limit in the number of previous lines of therapy. For Phase 2: Patients may have received previous adjuvant treatment with gemcitabine with or without radiotherapy for pancreas cancer. [9] Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. [10] Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial until the patient's physicians deems it safe to become pregnant or father a child. [11] Females with child bearing potential must have had a negative urine pregnancy test ≤7 days prior to the first dose of study drug. [13] Prior radiation therapy for treatment of cancer other than pancreatic is allowed to <25% of the bone marrow, and patients must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. [14] Baseline ECG QTc interval corrected by Bazett's method (should be <450 msec for males and <470 msec for females. |
| Fase II: maschi o femmine di età pari o superiore a 18 anni con adenocarcinoma del pancreas non resecabile localmente avanzato (stadio II/III) o metastatico (stadio IV) confermato istologicamente o citologicamente. |
|
| E.4 | Principal exclusion criteria |
| [15] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [16] Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator [17] Have symptomatic central nervous system malignancy or metastasis [18] Have current active infection that would, in the opinion of the investigator, compromise the patient's ability to tolerate therapy. [19] Females who are pregnant or lactating. [20] Have known positive test results in human immunodeficiency virus XML File Identifier: RbejZKBN5vo9DKFIBouWRDUVWFY= Page 21/32 (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) [21] Phase 2 only: Endocrine pancreatic tumors or ampullary cancer. [22] Phase 1: Patients with acute or chronic leukemia or with any other disease likely to have a significant bone marrow infiltration [23] Have previously completed or withdrawn from this study or any other study investigating LY2603618 or any other Chk-1 inhibitor. [24] Have known allergy to gemcitabine or LY2603618 or any ingredient of gemcitabine or LY2603618. [25] Has an abnormal ECG result that would put the patient at unnecessary risk in the opinion of the investigator. [26] Have conduction abnormalities, ischemic changes such as prior Qwave myocardial infarction and/or marked ischemic ST and T wave, and arrhythmias such as persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation. |
| I pazienti non devono essere affetti da tumori pancreatici endocrini né da carcinoma ampollare. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Phase II: OS in patients with stage II-IV unresectable pancreatic cancer who received LY2603618 and gemcitabine combination arm compared to OS on the gemcitabine only. |
| Fase II: Sopravvivenza globale in pazienti con tumore pancreatico non operabile stadio II-IV non operabile, che ricevono LY2603618 e gemcitabina in combinazione paragonato a Gemcitabina da sola. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 9 months after 99th patient enrolled |
| 9 mesi dopo l'arruolamento del novantanovesimo paziente |
|
| E.5.2 | Secondary end point(s) |
| To characterize further the safety and toxicity profile of LY2603618 when administered after gemcitabine and to compare it to the safety profile of gemcitabine monotherapy in the advanced pancreatic cancer population. To estimate other time-to-event variables, such as PFS and duration of response. To explore the percentage change in tumor size at 8 weeks and the relationship with OS. To document response rate per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1). XML File Identifier: RbejZKBN5vo9DKFIBouWRDUVWFY= Page 22/32 To evaluate the pharmacokinetics of gemcitabine, deoxydifluorouridine (dFdU) and LY2603618 in combination. To assess biomarker responses associated with LY2603618 and gemcitabine combination: Incorporation of nucleoside analogs (for example, gemcitabine) into the DNA of peripheral blood cells. Detection of p53 in tumor tissue. Detection of fragmented cytokeratin 18 cleaved at Asp396 (M30 neoantigen). To explore the evolution of CA19.9 in patients with pancreatic cancer for each treatment group and its relation with efficacy parameters. To explore the pharmacogenetic of drug metabolism enzyme and transporter (DMET) polymorphisms and its relation with the PK profile, safety and efficacy. To perform an exploratory assessment of QTc. |
| Caratterizzare la sicurezza e la tossicità di LY2603618 quando somministrato dopo gemcitabina e di confrontalo al profilo di sicurezza di gemcitabina in monoterapia in pazienti affetti da carcinoma pancreatico avanzato. Stimare altre viariabili come PFS e durata della risposta. Esplorare la percentuale di cambiamento delle dimensioni del tumore a 8 settimane e la relazione con la OS. Documentare il tasso di risposta secondo i criteri Recist 1.1 valutare la farmacocinetica di gemcitabina, deossifluoropiridina (dFdU) e LY2603618 in combinazione. Accertare le risposte dei biomarcatori associate con LY2603618 e gemcitabina in combinazione. Incorporazone degli analoghi nucleosidici nel DNA della cellule periferiche del sangue. Ricerca di p53 nel tessuto tumorale. Ricerca della citocheratina 18 frammentata legata all'Asp396 (neoantigene M30). Esplorare l'evoluzione del CA19.9 in pazienti con carcinoma pancreatico per ogni gruppo di trattamento e la sua relazione con i parametri di efficacia. Esplorare la farmacogenetica del metabolismo del farmaco , i polimorfismi dell'enzima del trasportatore (DMET)e la sua relazione con il profilo di PK, la sicurezza e l'efficacia. Svolgere una valutazone del QTc |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 9 months after 99th patient enrolled will be the final analysis of the study; however, patients may continue on study until progression or other reason for discontinuation which may be longer than 9 months after the 99th patient is enrolled |
| 9 mesi dopo l'arruolamento del novantanovesimo paziente sarà svolta l'analisi finale dei dati dellos tudio; in ogni modo, i pazienti possono continuare nello studio fino a progressione o altre motivazioni per la discontinuazione. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 21 |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 24 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 36 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
