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A Phase 1 Study of Picoplatin in Subjects With Advanced Non-Hematological Malignancies With Emphasis on Cardiac Repolarization

Phase 1
18 Years
Open (Enrolling)
Solid Tumors

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Trial Information

A Phase 1 Study of Picoplatin in Subjects With Advanced Non-Hematological Malignancies With Emphasis on Cardiac Repolarization

Phase 1 and 2 studies have demonstrated that picoplatin, a next-generation platinum analogue
designed to avoid drug resistance, has activity when administered IV in a variety of
cancers. Preclinical and clinical studies indicate that picoplatin may be effective in
platinum refractory or resistant cancer.

Preclinical data in beagle dogs have shown that picoplatin had no effect on cardiovascular
function, including the QT interval. In the cumulative human trial experience, the
cardiovascular serious adverse events that have occurred are consistent with events expected
in patients with advanced malignant disease and do not suggest any propensity toward
drug-related serious ventricular arrhythmias or sudden death.

The purpose of this trial is to conduct a formal study to specifically evaluate the effect
of picoplatin on the QT/QTc interval as measured by the ECG, and to correlate QTcF interval
with plasma total and ultrafilterable platinum concentrations. This study is also being
conducted to ensure the safety of picoplatin with regard to the QT/QTc interval. Patients
who choose to participate in this study will also be given the opportunity to continue to
receive picoplatin until limited by toxicity or disease progression.

Inclusion Criteria:

- 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
tumor involvement).

- 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.

Exclusion Criteria:

- 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

- 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).

Type of Study:


Study Design:

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

ECG interval change

Outcome Time Frame:

24 hours

Safety Issue:


Principal Investigator

Robert Earhart, MD, PhD

Investigator Role:

Study Director

Investigator Affiliation:

Poniard Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

June 2008

Completion Date:

July 2009

Related Keywords:

  • Solid Tumors
  • Bladder Cancer
  • Breast Cancer
  • Colorectal Cancer
  • Gastrointestinal Neoplasm
  • Head and Neck Cancer
  • Lung Cancer
  • Ovarian Cancer
  • Pancreatic Cancer
  • Prostrate Cancer



Swedish Cancer Institute Seattle, Washington  98104
Georgia Cancer Specialists Decatur, Georgia  30033
Moores UCSD Cancer Center La Jolla, California  92093-0658
Premiere Oncology Santa Monica, California  90404
Premiere Oncology of Arizona Scottsdale, Arizona  85260
UNM Cancer Center Albuquerque, New Mexico  87106
Northwest Medical Specialities Tacoma, Washington  98405