E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic pancreatic cancer |
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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 | Yes |
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 |
Protocol CO-101-001 PK-ECG substudy
To correlate PK variables with ECG changes in a subset of patients
Patients from several (4–6) preselected centers with suitable facilities will participate in a dedicated intensive PK-ECG substudy to compare standard PK variables of gemcitabine with CO-1.01 and to correlate these with ECG and Holter monitor changes. It is anticipated that one formulation improvement will be introduced during the course of the study. Each treatment group and formulation improvement will include approximately 10 patients (i.e., n = 20 to 40 patients).
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 |