E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced pancreatic cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
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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 primary objective of this study is: 1. Determine the maximum tolerated dose and recommended phase II dose of temsirolimus and gemcitabine in patients with pancreatic cancer. 2. To estimate the progression free survival in patients treated with the temsirolimus+gemcitabine combination.
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E.2.2 | Secondary objectives of the trial |
The secondary endpoints of the trial are: · To explore for potential correlations of tumor molecular profile with clinical outcome in patients treated at the recommended doses. · To estimate the Quality of Life benefits measured by the EuroQoL 5D scale. · To estimate the overall survival of the combination at trial closure. · To evaluate the nature, incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of the combination of temsirolimus and gemcitabine.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of written informed consent 2. Age 18 years or older 3. Histologic proof of pancreatic cancer 4. Performance status between 50% and 100% on the Karnofsky scale 5. Life expectancy of greater than 12 weeks 6. Prior radiotherapy is allowed except for evaluable sites 7. Measurable or evaluable disease as according to RECIST 8. All females of childbearing potential must have a negative serum or urine pregnancy test obtained within 2 days prior to initiation of treatment 9. WBC>4000/μl, platelets > 100,000/μl and a hemoglobin level > 9.5 g/dl. Adequate baseline hepatic function, defined as a total bilirubin level < 2 mg/dl, SGPT and SGOT < 3 times the upper limits of normal, unless the liver is involved, in which case the transaminase levels could be up to five times the upper limits of normal. Creatinine < 1.5 mg/dl or creatinine clearance > 60 ml/min. 10 Provision of adequate paraffin-embedded tumor tissue for translational studies and 10 ml peripheral blood for DNA study.
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E.4 | Principal exclusion criteria |
1. Patients with ampullary, periampullary, bile duct cancers or endocrine tumors of the pancreas 2. History of atrial or ventricular arrhythmias and/or history of congestive heart failure, even if medically controlled. History of clinical and electrocardiographically documented myocardial infarction within the last 6 months from study entry 3. Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded) 4. Pre-existing motor or sensory neurotoxicity grade 2 according to the WHO criteria (intolerable paresthesia and/or marked motor loss or worse) 5. History of previous chemotherapy 6. Symptomatic brain metastases 7. Known, severe hypersensitivity to temsirolimus or any of the excipients of this product 8. Other coexisting malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ 9. Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy 10. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (eg unstable or uncompensated respiratory, cardiac, hepatic or renal disease) 11. Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater or equal than 3 times the ULRR if no demonstrable liver metastases or greater than 5 times the ULRR in the presence of liver metastases 12. Active infection or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial/ receive protocol treatment 13. Pregnancy or breast feeding 14. Concomitant use of Cyp3 A inducers (phenytoin, carbamazepine, rifampicin, barbiturates or St John’s Wort) should be avoided and as should treatment wih strong CyP 3A inhibitors 15. Treatment with a non-approved or investigational drug within 30 days before Day 1 of trial treatment 16. Hypersensitivity to gemcitabine
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I Determine the feasibility and MTD for a combination of temsirolimus and gemcitabine Phase II The primary end-point of the phase II study will be the 6-month Progression-Free-Survival.
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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 | No |
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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
maximum tolerated dose in combination |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
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 | Information not present in EudraCT |
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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Until progression or unacceptable toxicity or voluntary withdrawal |
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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 | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |