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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
Michael Prados, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00734682
First received: August 13, 2008
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Glioblastoma
Gliosarcoma
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Anaplastic Mixed Oligoastrocytoma
Malignant Astrocytoma NOS
Drug: Nanoliposomal CPT-11
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Nanoliposomal CPT-11 (NL CPT-11) in Patients With Recurrent High-Grade Gliomas

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the maximum tolerated dose of NL CPT-11 in these patient populations. [ Time Frame: 1-2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: August 2008
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant glioma include glioblastoma multiforme (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).
  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information. Patients must be registered in UCSF Cancer Center database prior to treatment with study drug.

    • 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: 28 days from any investigational agent, 28 days from prior cytotoxic therapy, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration, and 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count).
  • 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) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion. - -Patients must have shown unequivocal 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. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
  • 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. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
  • Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 42 days from the completion of radiation therapy to registration date.
  • Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, MR spectroscopy or surgical documentation of disease.
  • Women of childbearing potential must have a negative ß-HCG pregnancy test documented within 14 days prior to registration. Female patients of childbearing potential are those who are not either surgically sterile (having undergone hysterectomy and/or bilateral salpingoophorectomy) or at least 50 years old and have had no menses for at least 24 months.
  • Patients may have had treatment for any number of prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemotherapy if that was used as initial therapy).

Exclusion Criteria:

  • Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
  • 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 be pregnant because animal studies show that NL CPT-11 is teratogenic.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00734682

Contacts
Contact: Ashley DeSilva 415-353-2653 DeSilvaAA@neurosurg.ucsf.edu
Contact: Thelma Munoz 415-353-2173 munozt@neurosurg.ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Michael Prados, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Michael Prados, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: Michael Prados, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00734682     History of Changes
Obsolete Identifiers: NCT00745082
Other Study ID Numbers: 08103
Study First Received: August 13, 2008
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Glioblastoma
Gliosarcoma
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Anaplastic Mixed Oligoastrocytoma
Malignant Astrocytoma NOS
Nanoliposomal CPT-11
liposomal irinotecan

Additional relevant MeSH terms:
Oligodendroglioma
Astrocytoma
Glioblastoma
Gliosarcoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014