A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas

January 5, 2015 updated by: Michael Prados, University of California, San Francisco
This is a Phase I study of Nanoliposomal CPT-11 in patients with Recurrent high-grade gliomas. Patients must have a histologically proven intracranial malignant glioma, which includes glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified). Patients who are wild type or heterozygous for the UGT1A1*28 gene will received Nanoliposomal CPT-11. The total anticipated accrual will be approximately 36 patients (depending upon the actual MTD). The investigators hypothesis is that this new formulation of CPT-11 will increase survival over that seen in historical controls who have recurrent gliomas because CPT-11 will be encapsulated in a liposome nanoparticle, which has been seen to reduce toxicities from the drug.

Study Overview

Detailed Description

Patients with recurrent malignant glioma will receive Nanoliposomal CPT-11 at the time of relapse. The dose will be adjusted according to a phase-1 dose escalation scheme. Patients will receive drug intravenously every 3 weeks until tumor progression or excessive toxicity. Weekly follow up will occur to assess toxicities during the DLT phase of the trial. Patients will have different dose escalation if UGT1A1 is 6/6 versus UGT1A1 is 6/7. Patients with UGT 1A1 of 7/7 will not be eligible. All patients must have UGT 1A1 status know as an eligibility requirement. Patients will be followed for both toxicity and progression, and progression will be evaluated by MR imaging every 6 weeks. Pharmacokinetics will be obtained in the first treatment cycle.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with histologically proven intracranial malignant glioma are eligible . -All patients must sign an informed consent

    • Patients must be > 18 years old, and with a life expectancy > 8 weeks.
    • Patients must have a Karnofsky performance status of > 60.
  • Patients must have recovered from the toxic effects of prior therapy
  • Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL and/or creatinine clearance > 60 cc/min) Patients must have shown radiographic evidence for tumor progression by MRI or CT scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. -Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:

    • They have recovered from the effects of surgery.
    • Residual disease following resection of recurrent malignant glioma is not mandated for eligibility into the study.
  • Patients must have failed prior radiation therapy
  • Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease
  • Women of childbearing potential must have a negative ß-HCG pregnancy test documented within 14 days prior to registration.
  • Patients may have had treatment for any number of prior relapses.

Exclusion Criteria:

  • Patients must not have any significant medical illnesses that in the investigator opinion cannot be adequately controlled
  • Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
  • Patients must not have active infection or serious intercurrent medical illness.
  • Patients must not be pregnant/breast feeding and must agree to practice adequate contraception.
  • Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
  • Patients must not have received prior therapy with irinotecan.
  • Patients with 7/7 (homozygous) UGT1A1*28 genotyping will be excluded from the study.
  • Patients receiving enzyme-inducing anticonvulsants or other enzyme inducing drugs are excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nanoliposomal CPT-11
All patients are treated with nanoliposomal CPT-11
Depending on UGT1A1 genotyping status, patients are either given a starting dose of 120 mg/m^2 (wild type) or 60 mg/m^2 IV q3 weeks.
Other Names:
  • NL CPT-11
  • liposomal irinotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To assess the safety and pharmacokinetics of NL CPT-11 in patients with recurrent malignant glioma stratified based on UGT1A1 genotyping.
Time Frame: 1-2 years
1-2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine the maximum tolerated dose of NL CPT-11 in these patient populations.
Time Frame: 1-2 years
1-2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Michael Prados, MD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

August 13, 2008

First Submitted That Met QC Criteria

August 13, 2008

First Posted (Estimate)

August 14, 2008

Study Record Updates

Last Update Posted (Estimate)

January 7, 2015

Last Update Submitted That Met QC Criteria

January 5, 2015

Last Verified

December 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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