Safety Study of PRLX 93936 in Patients With Advanced Solid Tumors

Cancer Clinical Trial

Official title:

A Phase I, Multi-center, Open-Label, Dose-Escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of PRLX 93936 Administered Intravenously Daily for Five Days Followed by a 23-Day Rest Period in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00528047
• Other study ID #: PRLX93936-0001
• Status: Completed
• Phase: Phase 1
• First received: September 7, 2007
• Last updated: January 3, 2012
• Start date: August 2007
• Est. completion date: November 2011

Study information

• Verified date: January 2012
• Source: Prolexys Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the safety of PRLX 93936 and see what kind of effect it has on patients and their cancer. This study will also determine the highest dose of PRLX 93936 that can be given without causing adverse side effects and the dose of PRLX 93936 that should be used in future studies.

Description:

This study will assess the safety, pharmacokinetics, and pharmacodynamics of PRLX 93936 administered intravenously over 1 hr daily for 5 days in patients with advanced solid tumors. Patients will be evaluated prior to dosing, during dosing and following dosing, on a 28-day cycle. Tumor response will be evaluated every other cycle.

Three patients will be assigned per dose level until the Maximum Tolerated Dose (MTD) is reached or a a Dose-Limited Toxicity (DLT) is encountered. Sequential cohorts of three patients will be treated with escalating doses until the Maximum Tolerated Dose (MTD) is reached.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: November 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed solid tumors

• Tumor progression after receiving standard/approved chemotherapy and for whom no available treatment provides clinical benefit

• One or more metastatic tumors measurable on a CT scan or MRI per RECIST criteria

• ECOG performance 0-1

• Life expectancy of at least 3 months

• Age >/= 18 years

• A negative pregnancy test (if female of child-bearing potential)

• Acceptable liver function:

• Bilirubin </= 1.5 times the Upper Limit of Normal (ULN)

• AST (SGOT), ALT (SGPT) and Alkaline phosphatase </= 2.5 times ULN (if liver metastases are present, then </= 5 times ULN is allowed)

• Acceptable renal function:

• Serum creatinine within normal limits, OR calculated creatinine clearance >/= 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal

• Acceptable hematologic status:

• Granulocyte count >/= 1500 cells/mm3

• Platelet count >/= 100,000 (plt/mm3)

• Hemoglobin >/= 9.0 g/dL

• Urinalysis: no clinically significant abnormalities

• Acceptable coagulation status:

• PT within normal limits

• aPTT within normal limits

• Completed any chemotherapy, major surgery, or irradiation at least four weeks before enrollment in this study (six weeks for mitomycin-C or nitrosoureas, and two weeks for "targeted" therapies such as kinase inhibitors). Patient must have recovered from all toxicities incurred as a result of previous therapy.

• QT intervals of QTC </= 450 msec for men and </= 470 msec for women (as measured by Hodges equation)

• Left ventricular ejection fraction >/= 50% by 2D Echocardiogram (or > institutional lower limits of normal)

Exclusion Criteria:

• NYHA Class III or IV, cardiac disease, myocardial infarction within the past six months, unstable arrhythmia, or evidence of ischemia on ECG

• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

• Pregnant or nursing women

• Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within four weeks prior to study entry (six weeks for mitomycin-C or nitrosoureas and two weeks for targeted therapies such as kinase inhibitors).

• Unwillingness or inability to comply with protocol procedures

• Known current infection with HIV, hepatitis B or hepatitis C

• Currently receiving any other investigational agent

• Currently receiving medications metabolized by the cytochrome P450 3A4 enzyme pathway

• Presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with brain metastases which are well controlled (patients not taking dexamethasone or anti-seizure medication >/= three months after treatment) may be enrolled.

• Any other severe concurrent disease, which in the judgement of the investigator would make the patient inappropriate for the study

• Diagnosis of hypertension

• Previously enrolled in this trial

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• PRLX 93936
PRLX 93936 will be administered intravenously over one hour daily for 5 days.

Locations

Country	Name	City	State
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	TGen Clinical Research Services at Scottsdale Healthcare	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Prolexys Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical laboratory tests		Weekly	Yes
Primary	Vital signs		Daily during dosing, then weekly during followup	Yes
Primary	Electrocardiograms (ECGs)		Multiple times during dosing, then weekly during followup	Yes
Primary	Echocardiograms (ECHO)		Baseline and every other cycle	Yes
Secondary	Tumor assessment		Baseline and every other cycle	No
Secondary	Blood sampling for pharmacokinetics		Days 1 and 5 of dosing	Yes