A Phase 1 Study of Picoplatin in Subjects With Advanced Non-Hematological Malignancies With Emphasis on Cardiac Repolarization
- Documented histological or cytological diagnosis of non-hematological malignancy.
- Subjects for whom, in the opinion of the investigator, treatment with single agent
picoplatin is appropriate.
- 18 years of age or older.
- ECOG performance status 0-2.
- An acceptable screening ECG.
- The following laboratory values:
- ANC ≥ 1500 cells/mm3 (without use of myeloid growth factors).
- Hemoglobin ≥ 10.0 g/dL (may be achieved with transfusion or growth factors).
- Platelet count ≥ 100,000/mm3 (without platelet transfusions in the past 10 days).
- Serum creatinine ≤ 1.5 x ULN.
- Total bilirubin ≤ 1.5 x ULN.
- AST/SGOT and ALT/SGPT ≤ 2.5 x ULN (up to 5.0 x ULN in the event of documented hepatic
- Serum potassium and magnesium within institutional normal limits. PT, aPTT ≤ 1.2 x
- Recovery period ≥ 4 weeks since major surgery, any chemotherapy (≥ 6 weeks for
treatment with mitomycin or any nitrosourea), any biological therapy, any
investigational therapy or any change in usage of "alternative therapies".
- Recovery period ≥ 2 weeks since any radiation therapy.
- Willing, available and able to comply with all protocol requirements including
dietary schedule and restrictions.
- Written informed consent obtained prior to any screening procedures.
- Symptomatic or uncontrolled brain metastases.
- Use of conventional granulocyte growth factors within the preceding 10 days or
pegfilgrastim within the past 21 days.
- Any concurrent severe and/or uncontrolled medical conditions which could compromise
participation in the study. For example,
- Unresolved toxicities from prior treatments of > Grade 1 (other than alopecia).
- Clinically significant infection.
- Known viral infections with hepatitis B or C or HIV.
- Clinically significant psychiatric illness.
- Any other systemic or localized disease or therapy likely to interfere with tolerance
of chemotherapy or requirements of study participation.
- History of unexplained syncope within the last two months or a family history of
sudden unexplained death.
- Cardiac contraindications to study participation, including:
- History of serious cardiac disease, defined as myocardial infarction within three
months of enrollment, congestive heart failure classified by the New York Heart
Association as Class III or IV, clinically significant cardiac arrhythmias, poorly
controlled or unstable angina or electrocardiographic evidence of acute ischemia.
- Implantable pacemaker or automatic implantable cardioverter defibrillator.
- Congenital long QT syndrome or family history of long QT syndrome.
- If male, QTc > 450 ms; if female, QTc > 460 ms.
- PR duration > 240 ms; QRS > 110 ms. Complex arrhythmias (significant ventricular
tachycardia, Mobitz block, bifascicular AV block) on the screening ECG.
- Atrial fibrillation or flutter. Complete left bundle branch block; use of an obligate
- Current use of anticoagulants or anti-platelet drugs, including aspirin, warfarin,
enoxaparin, clopidogrel, or heparin (use of heparin for central venous port
maintenance is acceptable).
- Ongoing bleeding or history of clinically significant bleeding within the last 6
months (unless the etiology of the prior bleeding has been identified and corrected).
- Concurrent medications that prolong the QT interval (including cisapride,
erythromycin, antipsychotics or tricyclic antidepressants, quinidine, procainamide,
disopyramide, amiodarone or sotalol), or any agent classified as either "Drugs with
Risk of Torsades de Pointes" or "Drugs with Possible Risk of Torsades de Pointes" on
the website www.torsades.org.
- Female subjects who are pregnant or breast feeding.
- Subjects of reproductive potential not willing to use an effective method of
contraception during the study (from first day of and until 1 month after study drug
- Conditions that may interfere with QTc analysis:
- Allergy to ECG electrodes.
- Any condition that impairs the placement of ECG electrodes or the interpretation of
ECGs (including but not limited to breast implants).