E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable Locally Advanced/ Metastatic Adenocarcinoma of the Pancreas |
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E.1.1.1 | Medical condition in easily understood language |
Unresectable Locally Advanced/ Metastatic Adenocarcinoma of the Pancreas |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001141 |
E.1.2 | Term | Adenocarcinoma |
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 |
The objective of the study is to assess the safety, efficacy and quality of life of a combination therapy of EndoTAG-1 plus gemcitabine vs. gemcitabine monotherapy in patients with locally advanced and/or metastatic adenocarcinoma of the pancreas eligible for second-line therapy after failing first-line therapy with FOLFIRINOX. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of twice weekly infusions of EndoTAG-1 with weekly infusions of gemcitabine versus gemcitabine monotherapy according to: -Incidence and percentage of subjects with treatment-emergent adverse events (TEAEs) -Laboratory abnormalities (hematology, coagulation parameters, clinical chemistry) -Dose reductions, pausing, and/or discontinuation of EndoTAG-1 and/or gemcitabine |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1-Age ≥ 18 years 2-Written informed consent 3-Histologically or cytologically confirmed adenocarcinoma of the pancreas 4-Metastatic or locally advanced disease that is considered unresectable 5-Measurable / assessable disease according to RECIST v.1.1 6-Documented disease progression on first line FOLFIRINOX 7-Negative pregnancy test 8-Both male and female patients and their partners of childbearing potential must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or one of the following methods of birth control (intrauterine devices, tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of reproductive potential during the course of the study and for 90 days after last treatment (excluding women who are not of childbearing potential and men who have been sterilized). 9-ECOG performance status 0 or 1
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E.4 | Principal exclusion criteria |
1-Cardiovascular disease, New York Heart Association (NYHA) III or IV 2-History of severe supraventricular or ventricular arrhythmia 3-History of coagulation or bleeding disorder 4-History of acute myocardial infarction within 6 months before randomization 5-History of congestive heart failure 6-Acute or chronic inflammation (autoimmune or infectious) 7-Significant active/unstable non-malignant disease likely to interfere with study assessments 8-Laboratory tests (hematology, chemistry) outside specified limits: a-WBC ≤ 3 x 10³/mm³ b-ANC ≤ 1.5 x 10³/mm³ c-Platelets ≤ 100,000/mm³ d-Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l) e-aPTT > 1.5 x ULN f-Serum creatinine > 2.0 mg/dl (> 176.8 µmol/l) g-AST and/or ALT > 2.5 x ULN; for patients with significant liver metastasis AST and/or ALT > 5 x ULN h-Alkaline phosphatase > 2.5 x ULN i-Total bilirubin > 2 x ULN j-Albumin < 2.5 g/dL 9-Clinically significant ascites 10-Any anti-tumor treatment (except FOLFIRINOX as the first-line therapy) for pancreatic adenocarcinoma before enrollment. Note: Patients who have undergone surgical interventions for pancreatic adenocarcinoma will be eligible. 11-Any radiotherapy for pancreatic adenocarcinoma before enrollment except for treatment of bone metastases if target lesions are not included in the irradiated field 12-Major surgery < 4 weeks prior to enrollment 13-Pregnant or nursing 14-Investigational medicinal product < 4 weeks of enrollment 15-Documented HIV history 16-Active hepatitis B infection requiring acute therapy Note: Subjects infected by the hepatitis B virus will be eligible for the study if they have no signs of hepatic decompensation and meet the liver function tests eligibility criteria. 17-Known hypersensitivity to any component of the EndoTAG-1 and/or gemcitabine formulations 18-History of malignancy other than pancreatic cancer < 3 years prior to enrollment, except non-melanoma skin cancer or carcinoma in situ of the cervix treated locally 19-Vulnerable populations (e.g. subjects unable to understand and give voluntary informed consent) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS) Overall survival time is defined as time from randomization to death from any cause or last day known to be alive. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1-Progression Free Survival (PFS) Progression Free Survival time is defined as the time from randomization to either first observation of progressive disease or occurrence of death. 2-Percentage of subjects with Objective Response (OR) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1)* Percentage of subjects with objective response is based on assessment of complete response (CR) or partial response (PR) according to RECIST v.1.1. 3-Duration of Response (DR)* Duration of Response is defined as the time from the first documentation of objective tumor response (date of the first CR or PR) to objective tumor progression or death due to any cause. 4-Percentage of subjects with disease control according to RECIST v.1.1* Percentage of subjects with disease control is based on assessment of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST v.1.1 5-Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0- 100 scale; higher score=better level of functioning or greater degree of symptoms. Change from baseline=Cycle/Day score minus baseline score. 6-Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score QLQ-PAN26 consists of 26 questions (Qs) relating to disease symptoms, treatment (Tx) side effects and emotional issues specific to pancreatic cancer (PC). Questions include on altered bowel habits, pain, dietary changes, disease and Tx-related symptoms and issues related to the emotional and social well-being of participants with PC. All 26 Qs are answered on 4-point Likert scale ranging from '1=not at all' to 4='very much' and subsequently transformed into scales that range from 0-100; higher scores= greater degree of symptoms or treatment side effects and emotional issues. 7-Serum Carcinoma Antigen 19-9 (CA 19-9) response rate Responders are defined as subjects with a reduction in CA 19-9 levels by least 50% from baseline to the end of cycle 1 (or end of full treatment course).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression Free Survival time is defined as the time from randomization to either first observation of progressive disease or occurrence of death. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Gemcitabine Hydrochloride USP |
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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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Israel |
Korea, Republic of |
Russian Federation |
Taiwan |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 20 |