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

Primary Purpose

Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nanoliposomal CPT-11
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Mixed Oligoastrocytoma, Malignant Astrocytoma NOS, Nanoliposomal CPT-11, liposomal irinotecan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California, San Francisco

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nanoliposomal CPT-11

Arm Description

All patients are treated with nanoliposomal CPT-11

Outcomes

Primary Outcome Measures

To assess the safety and pharmacokinetics of NL CPT-11 in patients with recurrent malignant glioma stratified based on UGT1A1 genotyping.

Secondary Outcome Measures

To determine the maximum tolerated dose of NL CPT-11 in these patient populations.

Full Information

First Posted
August 13, 2008
Last Updated
January 5, 2015
Sponsor
University of California, San Francisco
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1. Study Identification

Unique Protocol Identification Number
NCT00734682
Brief Title
A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas
Official Title
A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma
Keywords
Glioblastoma, Gliosarcoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Mixed Oligoastrocytoma, Malignant Astrocytoma NOS, Nanoliposomal CPT-11, liposomal irinotecan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nanoliposomal CPT-11
Arm Type
Experimental
Arm Description
All patients are treated with nanoliposomal CPT-11
Intervention Type
Drug
Intervention Name(s)
Nanoliposomal CPT-11
Other Intervention Name(s)
NL CPT-11, liposomal irinotecan
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
To determine the maximum tolerated dose of NL CPT-11 in these patient populations.
Time Frame
1-2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Prados, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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