E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with metastatic pancreatic adenocarcinoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
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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 efficacy of CO-1.01 and gemcitabine in patients with metastatic pancreatic adenocarcinoma and low human equilibrative nucleoside transporter 1 (hENT1) expression |
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E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of CO-1.01 and gemcitabine in patients with metastatic pancreatic adenocarcinoma and known hENT1 status (all patients and high hENT1 expression). • To compare the tolerability and toxicity of CO-1.01 with gemcitabine. • To compare changes in pain severity in patients receiving CO-1.01 and gemcitabine. • To compare changes in health status in patients receiving CO-1.01 and gemcitabine. • To correlate PK variables with ECG changes in a subset of patients (PK substudy). |
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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 |
FARMACOCINETICA/FARMACODINAMICA: Versione:1 Data:2010/01/15 Titolo:Protocol CO-101-001 PK-ECG substudy Obiettivi:Confrontare,in un sottogruppo limitato di pazienti, da preselezionati centri, i parametri standard di PK della gemcitabina con CO-1.01 e correlare questi valori con i cambiamenti dell`ECG. SI anticipa che una miglioramento della formulazione sara` introdotto nel corso dello studio. Ogni gruppo di trattamento e miglioramento della formulazione includera` circa 10 pazienti (quindi n= da 20 a 40 pazienti)
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E.3 | Principal inclusion criteria |
Patients are eligible for the study if all of the following criteria are met: • Metastatic pancreatic adenocarcinoma (i.e., Stage 4). • Histological/cytological confirmation of metastatic tissue (not primary tumor) by a central pathology laboratory (H&E stain) to ensure sufficient material is available for later hENT1 analysis. − Biopsy from metastases must be obtained ≥3 months after adjuvant chemotherapy (if applicable). − Paraffin block sufficient for preparing ≥6 unstained slides for central storage and subsequent hENT1 analysis is required. • Adjuvant chemotherapy/radiotherapy ≥6 months prior to randomization. • Palliative radiotherapy (if administered) ≥1 month prior to randomization. • CT scan ≤30 days prior to randomization. • Performance Status (ECOG) 0 or 1. • Estimated life expectancy ≥12 weeks. • Age ≥18 years. • Adequate hematological and biological function, defined as the following changes in the central laboratory values: Bone marrow function − Neutrophils ≥1.5 � 109/L − Platelets >100.0 � 109/L − Hemoglobin ≥10 g/dL Hepatic function − AST ≤2.5 � upper limit of normal (ULN); if liver metastases, ≤5 � ULN − Bilirubin ≤1.5 times ULN; if liver metastases, ≤3 � ULN − Albumin >3 g/dL − PT/PTT within 10% ULN Renal function − Serum creatinine ≤1.5 � ULN • Written consent on an IRB/IEC-approved Informed Consent Form prior to any study-specific evaluation. |
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E.4 | Principal exclusion criteria |
Patients are excluded from the study if any of the following criteria are met: • Prior palliative chemotherapy for pancreatic cancer. • Radical pancreatic resections (e.g., Whipple procedure) are not allowed < 6 months prior to randomization. Exploratory laparotomy, palliative (e.g., bypass) surgery, or other procedures (e.g., stents) are not allowed <14 days prior to randomization. In both cases the patient must be sufficiently recovered and stable. • Symptomatic brain metastases. • Participation in other investigational drug clinical studies ≤30 days prior to randomization. • Concomitant treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment, or immunotherapy) ≤30 days prior to randomization. • QTcF > 450 msec (male) or > 470 msec (female). • History of allergy to gemcitabine or eggs. • Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism). • Significant neurological or psychiatric disorder that would hamper protocol compliance. • Prior nonpancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery or radiotherapy alone must be in remission ≥3 years. Prior malignancies allowed irrespective of when they occurred are in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer. • Females who are pregnant or breastfeeding. • Refusal to use adequate contraception (Section 6.3) for fertile patients (females and males for 6 months after the last protocol-specified treatment). • Any other reason the investigator considers the patient should not participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The overall survival (OS) in patients with low hENT1 expression |
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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 | Yes |
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 | 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 | 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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 | Information not present in EudraCT |
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 |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |