A Prospective, Open-label, Single Center, Dose Finding Phase I-study With Atu027 (an siRNA Formulation) in Subjects With Advanced Solid Cancer
1. Histologically and/or cytologically proven advanced, recurrent or metastatic solid
malignancy for which standard curative or palliative measures do not exist, are no
longer effective, or are unlikely to be effective.
2. Age >/= 18 years.
3. ECOG performance score of 0-2.
4. Life expectancy of at least 3 months.
5. Subjects must have recovered from the acute reversible effects of previous
anti-cancer therapies. At least 30 days since major surgery and at least 5 half-lives
(t1/2) must have elapsed since treatment with any investigational agent.
6. Adequate marrow, hepatic, renal, and heart function at the time of screening.
7. Weight >/= 50kg.
8. Subjects must have at least one measurable lesion according to RECIST.
9. Women of childbearing potential must have a negative urine pregnancy test at
10. Women of childbearing potential and men must be willing to use highly effective
contraceptive methods during the course of the study and three months after.
11. Subjects must be willing and able (in the opinion of the investigator) to understand
the subject information and informed consent form and to comply with the study
protocol and procedures.
12. Subjects must be willing and able to give written informed consent.
1. Evidence of central nervous system (CNS) metastases.
2. Peripheral venous access insufficient to permit intravenous infusion or acquisition
of laboratory specimen.
3. Major surgery within 30 days prior to first study treatment.
4. Evidence that subject has only insufficiently recovered from the acute reversible
effects of previous anti-cancer therapies or surgery.
5. Abnormal hematologic parameters as defined:
- Neutrophil count < 1.500/mm3 (=1.5x10^9/l)
- Platelet count < 100.00/mm3 (=100x10^9/l)
- White blood cells < 3x10^9/l
- Hemoglobin < 9.0 g/l
6. Abnormal renal or hepatic function as defined:
- ASAT (SGOT), ALAT (SGPT) >/= 1.5xULN or >/= 2.0xULN in case of liver metastases
- Total bilirubin >/= 1.5xULN
- Creatinine clearance < 50ml/min calculated by the Cockroft-Gault formula
7. Weight < 50 kg.
8. Any concurrent disease, medical or social condition that could affect compliance with
the protocol or interpretation of results as judged by the investigator. In
particular, subjects with the following conditions are not allowed to enter the
- Poorly controlled Diabetes mellitus
- Lipid metabolism disorder (cholesterol and triglycerides >/= 1.5xULN), Refsum
- Myocardial infarction within six (6) months prior to enrollment or having
insufficient cardiac function defined as NYHA Grade 3 or 4, uncontrolled angina,
cardiomyopathy, severe uncontrolled ventricular arrhythmias, left bundle branch
block or electrocardiographic evidence of acute ischemic or active conduction
system abnormalities (e.g. long QT interval, Torsade de Pointes)
- Poorly controlled hypertension
- Severe dyspnea or severe pulmonary dysfunction
- Autoimmune and inflammatory disease
- Active infection or known bacteremia
- Known infection with HIV or chronic infection with hepatitis B or C virus
- History of acute or chronic pancreatitis
- Substance abuse
9. Prior gene transfer therapy.
10. Concurrent treatment with investigational or commercial agents or therapies
administered with the intention to treat the subject's malignancy.
11. Participation in any other clinical study or use of investigational device(s) during
participation in this study.
12. Known hypersensitivity to ingredients of the infusion solution.
13. Pregnant or nursing women or women of childbearing potential who are not willing to
use highly effective forms of contraception during participation in this study and at
least three months thereafter.
14. Male subjects with partners of child-bearing potential who are not willing to use
highly effective contraception during participation in this study and for at least
three months thereafter, unless surgically sterile.
15. Subject is a relative of, or staff directly reporting to the investigator or employee
of the sponsor.