UCSF BTC Clinical Trials

Study of Convection-Enhanced, Image-Assisted Delivery of Liposomal-Irinotecan In Recurrent High Grade Glioma

 

Summary

Chemotherapy treatment of high grade gliomas (HGG), among other brain tumors, faces several challenges including the effective delivery of drugs to the tumor site. This clinical trial tests the combination of two different strategies for the delivery of a chemotherapy drug in patients with HGG.

The first strategy involves convection enhanced delivery (CED), a strategy involving minimally invasive surgery that allows for the direct infusion of drugs into the tumor site. When the drug infusion includes gadolinium, an MR contrast agent, MRI can be used for real-time monitoring of drug infusion throughout the entire tumor site.

The second strategy involves liposomal-irinotecan, a formulation of the chemotherapy drug irinotecan that has been packaged into liposomes. Liposomes are tiny fluid-filled spheres whose surface is made of specialized molecules that allow it to cross the blood-brain barrier. By encapsulating irinotecan into liposomes (which is then called liposomal-irinotecan), the chemotherapy drug can more effectively access the brain while also limiting the toxicity of irinotecan in healthy tissue outside the brain. There is also experimental evidence that liposomal packaging extends the drug’s half life and improves its distribution within the tumor.

Although these delivery strategies were developed independently, this clinical trial will test the combination of liposomal-irinotecan and CED for the treatment of patients with HGG. Preliminary studies conducted in mouse models of glioblastoma indicate that liposomal-irinotecan is more effective when administered via CED instead of intravenously. This Phase I clinical trial will evaluate the dosage and effect of liposomal-irinotecan and gadolinium when administered via CED to patients with recurrent HGG.

 

Inclusion Criteria
  1. Patients with radiographically proven recurrent, intracranial high grade glioma will be eligible for this protocol. Patients must have evidence of tumor progression as determined by the Revised Assessment in Neuro-Oncology RANO criteria following standard therapy.
  2. High grade glioma includes glioblastoma multiforme (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified. (NOS)
  3. Magnetic resonance imaging (MRI) must be performed within 21 days prior to enrollment, and patients who are receiving steroids must be stable or decreasing for at least 5 days prior to imaging. If the steroid dose is increased between the date of imaging and enrollment, a new baseline MRI is required.
  4. Patients must have completed only 1 prior course of radiation therapy and must have experienced an interval of greater than 12 weeks from the completion of radiation therapy to study entry.
  5. Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade glioma is made.
  6. There is no limit as to the number of prior treatments but patients must have radiographic evidence of progressive disease
  7. Recurrent tumor must be a solid, single, supratentorial, contrast-enhancing HGG which conforms to the following volume according to the relevant treatment group Group Tumor volume: a.    Group 1: 1-4 cm3 b.    Group 2 : 1-4 cm3 c.    Group 3:  2-5 cm3 d.    Group 4 : 2-6 cm3
  8. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must be registered prior to treatment with study drug.
  9. Patients must be> 18 years old, and with a life expectancy > 8 weeks
  10. Patients with Karnofsky performance status of > 70.
  11. At the time of registration: Patients must have recovered from the toxic effects of prior therapy: > 10 days from any noncytotoxic investigational agent, >28 days from prior cytotoxic therapy or Avastin, >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). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
  12. Requirements for organ and marrow function as follows:
    1. Adequate bone marrow function:
      1. leukocytes > 3,000/mcL
      2. absolute neutrophil count > 1,500/mcL
      3. platelets > 100,000/mcL
    2. Adequate hepatic function:
      1. total bilirubin within normal institutional limits
      2. aspartate aminotransferase (AST) < 2.5 X institutional upper limit of normal
      3. alanine aminotransferase (ALT) < 2.5 X institutional upper limit of normal
    3. Adequate renal function:
      1. creatinine within normal institutional limits OR
      2. creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  13. The effects of nano liposomal irinotecan on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception: hormonal or barrier method of birth control; abstinence, etc. prior to study entry, for the duration of study participation, and for 6 months post drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  14. Women of childbearing potential must have a negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test documented within 14 days prior to treatment.
  15. Patients with prior therapy that included interstitial brachytherapy, or Gliadel wafers 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
  16. Patients must be able to have MRI brain imaging.

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

Exclusion Criteria
  1. 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
  2. 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.
  3. Patients must not have an active infection or serious intercurrent medical illness.
  4. Patients must not be pregnant/breast feeding and must agree to practice adequate contraception. 
  5. HIV-positive patients on combination antiretroviral therapy are ineligible
  6. Contrast-enhancing tumor which crosses the midline.
  7. Multi-focal disease
  8. Nonparenchymal tumor dissemination (e.g., subependymal or leptomeningeal)
  9. History of hypersensitivity reactions to products containing irinotecan (irinotecan), topotecan or other topoisomerase inhibitors, gadolinium contrast agents or lipid products
  10. Ongoing treatment with cytotoxic therapy
  11. Patients may not be on an enzyme-inducing anti-epileptic drug (EIAED). If previously on an EIAED, patient must be off for at least 10 days prior to CED infusion.

For the most up-to-date list of criteria, please visit clinicaltrials.gov.

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