PR-104 in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00349167

Last Updated: 2012-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2007-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as PR-104, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of PR-104 in treating patients with advanced solid tumors.

Detailed Description

OBJECTIVES:

Primary

• 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.

Secondary

• Characterize the pharmacokinetics of PR-104 and its alcohol metabolite in these patients.
• Assess evidence of antitumor activity of this drug in these patients.

Tertiary

• 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 study.

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PR-104

PR104 was administered as a 1-hr IV infusion every 21 days at doses ranging from 135 to 1400 mg/m2

Group Type: EXPERIMENTAL

PR-104

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Interventions

PR-104

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor, meeting 1 of the following criteria:

• Not amenable to standard therapy
• Refractory to conventional therapy
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy
• More than 2 weeks since prior hormonal therapy (except for androgen-deprivation therapy)
• 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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Proacta, Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark D. Pegram, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Countries

United States

References

Jameson MB, Rischin D, Pegram M, Gutheil J, Patterson AV, Denny WA, Wilson WR. A phase I trial of PR-104, a nitrogen mustard prodrug activated by both hypoxia and aldo-keto reductase 1C3, in patients with solid tumors. Cancer Chemother Pharmacol. 2010 Mar;65(4):791-801. doi: 10.1007/s00280-009-1188-1. Epub 2009 Dec 10.

Reference Type: RESULT

PMID: 20012293 (View on PubMed)

Other Identifiers

P30CA016042

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UCLA-0512034-01A

Identifier Type: -

Identifier Source: secondary_id

PROACTA-PR-104-1001

Identifier Type: -

Identifier Source: secondary_id

PR104-1001

Identifier Type: -

Identifier Source: org_study_id