PR-104 in Treating Patients With Advanced Solid Tumors

Proacta

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: PR-104

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00349167

UCLA-0512034-01A

PR104-1001

PROACTA-PR-104-1001

P30CA016042 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 1 patient group

PR-104

Experimental group

Description:

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

Treatment:

Drug: PR-104

Other: pharmacological study

Other: laboratory biomarker analysis