E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced pancreatic adenocarcinoma |
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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 | 10033599 |
E.1.2 | Term | Pancreatic adenocarcinoma 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 determine the recommended dose of AEG35156 when used in combination with gemcitabine.
To determine if AEG35156 can enhance the response rate of gemcitabine in patients with advanced pancreatic cancer. |
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E.2.2 | Secondary objectives of the trial |
To determine progression-free survival.
To establish the pharmacokinetics of AEG35156 and gemcitabine when used in combination. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with histologically or cytologically confirmed advanced pancreatic adenocarcinoma who are candidates for first-line gemcitabine therapy
Karnofsky performance greater than or equal to 70%
One or more metastatic tumors measurable by RECIST criteria on CT scan or MRI (Phase 2 part only)
Life expectancy of at least 3 months
Age greater than or equal to 18 years
Signed, written IRB-approved informed consent
A negative serum pregnancy test
Acceptable liver function: 1) Total bilirubin less than or equal to 1.5 times the Institution's upper limit of normal (ULN), 2) AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x ULN or less than or equal to 5 x ULN if there are documented liver metastases
Acceptable renal function: Serum creatinine within normal limits, OR calculated creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
Acceptable hematologic status: 1) Granulocyte greater than or equal to 1500 cells/microlitre, 2) Platelet count greater than or equal to 100,000 plt/microlitre, 3) Hemoglobin greater than or equal to 9.0 g/dL
Acceptable coagulation status: 1) PT within normal limits, 2) PTT within normal limits
For women of child-producing potential, the use of effective contraceptive methods during the study
Prior radiothrerapy for local disease is allowed provided disease progression has been documented, and treatment completed at least 4 weeks prior to registration. |
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E.4 | Principal exclusion criteria |
Prior chemotherapy for pancreatic cancer, except for 5-fluorouracil or gemcitabine given as a radiosensitizer.
Active progressive brain metastases including the presence of any related symptoms or need for corticosteroids. A CT or MRI scan of the head is necessary in patients with a history of brain metastases to document the stability of prior lesions.
Known bleeding diathesis or concurrent treatment with anticoagulants except patients on non-therapuetic line mantenance coumadin.
Pregnant or nursing women. NOTE: Women of child-bearing potential must agree to use adequate contraception (sterile or surgically sterile; hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Men who are unwilling to use acceptable forms of birth control when engaging in sexual contact with women of child bearing potential.
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
Known infection with HIV, hepatitis B, or hepatitis C.
Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
Patients who are currently receiving any other investigational agent. Subjects who have used a previous antisense oligonucleotide in the last 90 days will be excluded.
Unwillingness or inability to comply with procedures required in this protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1: The primary objective of the Phase 1 study is to determine the recommended dose of AEG35156 when used in combination with gemcitabine in patients with advanced pancreatic cancer. This determination will be based upon the development of DLT during the first cycle of therapy, and on pharmacokinetic determination for plasma AEG35156 and gemcitabine,obtained after the first combined administration of the two agents.
Phase 2: The Phase 2 is an open label, nonrandomized study. The primary objective of this study is to determine the objective response rate of AEG35156 when used in combination with gemcitabine in advanced pancreatic cancer. This determination will be based on objective tumor responses and progression-free survival. The tumor response will be evaluated at the end of every even numbered cycle (i.e., cycles 2, 4, 6, etc.) according to RECIST Response Criteria and the Choi Criteria. The RECIST Criteria will be used for response statistical analysis. The progression-free survival (PFS) will be measured from the treatment start date (date of first dose) to either the date the patient is first recorded as having disease progression (even if the patient went off treatment because of toxicity), or the date of death if the patient dies due to any causes before progression. Safety and tolerability, as measured by Grade 3-4 laboratory abnormalities related to study treatment, serious adverse events and adverse events will be assessed during the study through to 28 days post-last dose.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | No |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Historical response rate to gemcitabine alone |
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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 | 3 |
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 | 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 | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |