PNU 166148 in Treating Patients With Metastatic Solid Tumors

A Phase I Study to Evaluate MAG-CPT (PNU 166148) Given as One Single Intravenous Administration Every 4 Weeks in Patients With Advanced Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of PNU 166148 in treating patients who have metastatic solid tumors that have not responded to previous treatment.

Study Overview

• Status: Unknown
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: mureletecan

Detailed Description

OBJECTIVES: I. Determine the safety profile, maximum tolerated dose, and dose limiting toxicities of PNU 166148 in patients with metastatic, refractory solid tumors. II. Define a recommended dose of PNU 166148 for a Phase II study. III. Determine the pharmacokinetic profile and molecular weight distribution of PNU 166148 and the pharmacokinetic profile of free camptothecin in these patients. IV. Assess any evidence of antitumor activity in these patients treated with this regimen.

OUTLINE: This is a dose escalation, open label, multicenter study. Patients receive PNU 166148 IV over 30 minutes. Treatment repeats every 4 weeks for 3-6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of PNU 166148 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3-6 patients experience dose limiting toxicity. Patients are followed for 30 days, and then monthly thereafter only for resolution of adverse events that occurred while on study and were attributable to study drug, unless another antitumor treatment is begun.

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

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
    • Glasgow, Scotland, United Kingdom, G11 6NT
      • Beatson Oncology Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically proven metastatic, refractory solid tumors for which no curative therapy exists No more than 2 prior chemotherapy regimens for metastatic disease No prior high dose chemotherapy regimen requiring bone marrow transplantation or peripheral blood stem cell transplantation No hematologic malignancies No brain or leptomeningeal disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 2,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal (no greater than 1.5 times upper limit of normal (ULN) if liver metastases present) SGOT and SGPT normal (no greater than 5 times ULN if liver metastases present) Hepatitis B negative Renal: Creatinine less than 1.5 mg/dL EDTA clearance greater than 60 mL/min Other: Not pregnant or nursing Fertile patients must use effective contraception during and for 6 months after study No severe concurrent nonmalignant disease that would preclude protocol therapy HIV negative No AIDS related illness No mental incapacity

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 4 weeks since prior immunotherapy and recovered No concurrent biological response modifier therapy or immunotherapy No concurrent prophylactic growth factors Chemotherapy: See Disease Characteristics No prior camptothecins (e.g., irinotecan or topotecan) At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered No other concurrent chemotherapy Endocrine therapy: At least 4 weeks since prior hormonal therapy and recovered No concurrent corticosteroids used as anticancer therapy No other concurrent hormonal therapy Radiotherapy: No prior radiotherapy to greater than 25% of bone marrow At least 4 weeks since other prior radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified Other: No concurrent investigational drug or participation in other clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: University of Glasgow
• Investigators: Study Chair: Chris Twelves, MD, BMedSci, FRCP, University of Glasgow

Study record dates

Study Major Dates

• Study Start: June 1, 1999

Study Registration Dates

• First Submitted: December 10, 1999
• First Submitted That Met QC Criteria: June 16, 2004
• First Posted (Estimate): June 17, 2004

Study Record Updates

• Last Update Posted (Estimate): December 19, 2013
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: November 1, 2000

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CDR0000067285; CRC-BOC-98OMCP001; EU-99009; P-UPJOHN-98OMCP001