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A Phase I, Multi-Center, Open Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR-104 Given Every 3 Weeks in Patients With Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I, Multi-Center, Open Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR-104 Given Every 3 Weeks in Patients With Solid Tumors



- Evaluate the safety and tolerability of PR-104 in patients with advanced solid tumors.

- Determine the maximum tolerated dose of PR-104 in these patients.


- Characterize the pharmacokinetics of PR-104 and its alcohol metabolite in these

- Assess evidence of antitumor activity of this drug in these patients.


- Examine metabolic changes in tumors of these patients using fludeoxyglucose F 18
positron emission tomography scanning.

OUTLINE: This is a multicenter, open-label, prospective, uncontrolled, dose-escalation

Patients receive PR-104 IV over 60 minutes on day 1. Treatment repeats every 21 days in the
absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PR-104 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity.

Blood is collected at baseline and then periodically during study treatment for
pharmacokinetic and tumor marker studies. Patients undergo fludeoxyglucose F 18 positron
emission tomography scanning before beginning study treatment and after completion of course
2 to assess metabolic activity of the tumor.

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Inclusion Criteria


- Histologically or cytologically confirmed solid tumor, meeting 1 of the following

- Not amenable to standard therapy

- Refractory to conventional therapy

- Measurable or evaluable disease


- Karnofsky performance status 70-100%

- Life expectancy > 3 months

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin > 9 g/L (transfusion independent)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST ≤ 2.5 times ULN

- Creatinine clearance ≥ 60 mL/min

- PT/INR or aPTT ≤ 1.1 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 30 days after
completion of study treatment

- No significant cardiac comorbidity including any of the following:

- New York Heart Association class III-IV congenital heart failure

- LVEF < 40%

- Unstable angina

- Myocardial infarction within the past 6 months

- Ventricular arrhythmias requiring drug therapy

- Pacemaker or implanted defibrillator

- No ongoing coagulopathy

- No uncontrolled infection or infection requiring parenteral antibiotics

- No other significant clinical disorder or laboratory finding that would preclude
study treatment

- No known HIV positivity

- No known positivity for hepatitis B surface antigen or hepatitis C with abnormal
liver tests

- No known allergy to nonplatinum-containing alkylating agents


- Recovered from prior therapy

- More than 2 weeks since prior hormonal therapy (except for androgen-deprivation

- More than 4 weeks since prior major surgery

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

- More than 4 weeks since prior radiotherapy

- More than 1 month since prior investigational drugs, therapies, or devices

- No prior radiotherapy to > 25% of bone marrow

- No prior high-dose chemotherapy, either myeloablative or nonmyeloablative
(mini-allogeneic transplant)

- No more than 3 prior myelosuppressive chemotherapy regimens

- Concurrent steroids allowed provided dose is stable for ≥ 2 weeks and clinical
condition is stable for 1 month

- Nasal, opthalmologic, and topical glucocorticoid preparations allowed

- Physiologic hormone replacement therapies allowed (i.e., oral replacement
glucocorticoid therapy for adrenal insufficiency)

- No concurrent prophylactic hematopoietic growth factors

- No concurrent radiotherapy, including local palliative radiotherapy or systemic

- Radioisotopes for protocol specified positron emission tomography allowed

- No other concurrent investigational agents

- No other concurrent chemotherapy, radiotherapy (including palliative local
radiotherapy), hormonal therapy (except for androgen-deprivation therapy), and/or
biological therapy (including immunotherapy)

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Mark D. Pegram, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2005

Completion Date:

June 2007

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781