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BrUOG 329 GBM Onyvide With TMZ (329)

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ClinicalTrials.gov Identifier: NCT03119064
Recruitment Status : Recruiting
First Posted : April 18, 2017
Last Update Posted : January 7, 2019
Sponsor:
Collaborators:
Merrimack Pharmaceuticals
Rhode Island Hospital
Information provided by (Responsible Party):
Heinrich Elinzano, MD, Brown University

Brief Summary:
New treatments are greatly needed for patients with recurrent glioblastoma. Metronomic temozolomide is a standard treatment option but has, at best, modest activity. The nanoliposomal irinotecan may be much more active than the parent compound irinotecan since nanoliposomal irinotecan's ability to cross the blood brain barrier is improved. This phase I study will establish the MTD of the combination of nanoliposomal irinotecan in combination with temozolomide safety and preliminary clinical efficacy of the combination of nanoliposomal irinotecan and metronomic temozolomide.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Glioblastoma GBM Drug: Nanoliposomal Irinotecan Drug: Temozolomide Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BrUOG 329: Onivyde (Nanoliposomal Irinotecan) and Metronomic Temozolomide for Patients With Recurrent Glioblastoma: A Phase IB/IIA Brown University Oncology Research Group Study
Actual Study Start Date : November 30, 2017
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Experimental: Dose 1

Temozolomide: 50mg/m2/day until disease progression.

Nanoliposomal irinotecan :

Dose Level 1 50mg/m2 IV every 2 weeks

Drug: Nanoliposomal Irinotecan
Three patients will be accrued to level 1. If no dose limiting toxicities are observed following completion of 4 weeks (2 cycles) of treatment then accrual to dose level 2 will proceed (patients must be evaluated prior to their cycle 3 treatment and this will be used to confirm DLTs). If a DLT is observed in one of the first 3 patients in a dose level, then accrual for that level will be expanded to 6 patients. Accrual will continue in this way until the MTD of nanoliposomal irinotecan with temozolomide 50mg/m2/day is determined. Two or more instances of DLT in a cohort of 6 patients will result in the preceding dose level being defined as the MTD. If two or more instances of DLT in a cohort of 6 patients occurs in dose level 1 then dose level -1 of nanoliposomal irinotecan will be investigated. After determination of the MTD, the final cohort will be expanded so that a total of 25 patients are treated on study. The final cohort will be treated at the MTD.
Other Name: Onyvide

Drug: Temozolomide
Three patients will be accrued to level 1. If no dose limiting toxicities are observed following completion of 4 weeks (2 cycles) of treatment then accrual to dose level 2 will proceed (patients must be evaluated prior to their cycle 3 treatment and this will be used to confirm DLTs). If a DLT is observed in one of the first 3 patients in a dose level, then accrual for that level will be expanded to 6 patients. Accrual will continue in this way until the MTD of nanoliposomal irinotecan with temozolomide 50mg/m2/day is determined. Two or more instances of DLT in a cohort of 6 patients will result in the preceding dose level being defined as the MTD. If two or more instances of DLT in a cohort of 6 patients occurs in dose level 1 then dose level -1 of nanoliposomal irinotecan will be investigated. After determination of the MTD, the final cohort will be expanded so that a total of 25 patients are treated on study. The final cohort will be treated at the MTD.
Other Name: TMZ

Experimental: Dose 2

Temozolomide: 50mg/m2/day until disease progression.

Nanoliposomal irinotecan :

Dose Level 2 70 mg/m2 IV every 2 weeks

Drug: Nanoliposomal Irinotecan
Three patients will be accrued to level 1. If no dose limiting toxicities are observed following completion of 4 weeks (2 cycles) of treatment then accrual to dose level 2 will proceed (patients must be evaluated prior to their cycle 3 treatment and this will be used to confirm DLTs). If a DLT is observed in one of the first 3 patients in a dose level, then accrual for that level will be expanded to 6 patients. Accrual will continue in this way until the MTD of nanoliposomal irinotecan with temozolomide 50mg/m2/day is determined. Two or more instances of DLT in a cohort of 6 patients will result in the preceding dose level being defined as the MTD. If two or more instances of DLT in a cohort of 6 patients occurs in dose level 1 then dose level -1 of nanoliposomal irinotecan will be investigated. After determination of the MTD, the final cohort will be expanded so that a total of 25 patients are treated on study. The final cohort will be treated at the MTD.
Other Name: Onyvide

Drug: Temozolomide
Three patients will be accrued to level 1. If no dose limiting toxicities are observed following completion of 4 weeks (2 cycles) of treatment then accrual to dose level 2 will proceed (patients must be evaluated prior to their cycle 3 treatment and this will be used to confirm DLTs). If a DLT is observed in one of the first 3 patients in a dose level, then accrual for that level will be expanded to 6 patients. Accrual will continue in this way until the MTD of nanoliposomal irinotecan with temozolomide 50mg/m2/day is determined. Two or more instances of DLT in a cohort of 6 patients will result in the preceding dose level being defined as the MTD. If two or more instances of DLT in a cohort of 6 patients occurs in dose level 1 then dose level -1 of nanoliposomal irinotecan will be investigated. After determination of the MTD, the final cohort will be expanded so that a total of 25 patients are treated on study. The final cohort will be treated at the MTD.
Other Name: TMZ

Experimental: Dose 3

Temozolomide: 50mg/m2/day until disease progression.

Nanoliposomal irinotecan :

Dose Level 3 80mg/m2 IV every 2 weeks

Drug: Nanoliposomal Irinotecan
Three patients will be accrued to level 1. If no dose limiting toxicities are observed following completion of 4 weeks (2 cycles) of treatment then accrual to dose level 2 will proceed (patients must be evaluated prior to their cycle 3 treatment and this will be used to confirm DLTs). If a DLT is observed in one of the first 3 patients in a dose level, then accrual for that level will be expanded to 6 patients. Accrual will continue in this way until the MTD of nanoliposomal irinotecan with temozolomide 50mg/m2/day is determined. Two or more instances of DLT in a cohort of 6 patients will result in the preceding dose level being defined as the MTD. If two or more instances of DLT in a cohort of 6 patients occurs in dose level 1 then dose level -1 of nanoliposomal irinotecan will be investigated. After determination of the MTD, the final cohort will be expanded so that a total of 25 patients are treated on study. The final cohort will be treated at the MTD.
Other Name: Onyvide

Drug: Temozolomide
Three patients will be accrued to level 1. If no dose limiting toxicities are observed following completion of 4 weeks (2 cycles) of treatment then accrual to dose level 2 will proceed (patients must be evaluated prior to their cycle 3 treatment and this will be used to confirm DLTs). If a DLT is observed in one of the first 3 patients in a dose level, then accrual for that level will be expanded to 6 patients. Accrual will continue in this way until the MTD of nanoliposomal irinotecan with temozolomide 50mg/m2/day is determined. Two or more instances of DLT in a cohort of 6 patients will result in the preceding dose level being defined as the MTD. If two or more instances of DLT in a cohort of 6 patients occurs in dose level 1 then dose level -1 of nanoliposomal irinotecan will be investigated. After determination of the MTD, the final cohort will be expanded so that a total of 25 patients are treated on study. The final cohort will be treated at the MTD.
Other Name: TMZ




Primary Outcome Measures :
  1. MTD [ Time Frame: Every two weeks for 4 weeks ]
    To evaluate the maximum tolerated dose of nanoliposomal irinotecan with continuous low-dose temozolomide for patients with recurrent glioblastoma.

  2. Response [ Time Frame: Every 2 months on study treatment then very 3 months once treatment has stopped, until progression of disease up to 2 years. ]
    Preliminary response rate of nanaliposomal irinotecan with continuous low-dose temozolomide in patients with recurrent glioblastoma.

  3. PFS [ Time Frame: Every 2 months on study treatment then very 3 months once treatment has stopped, until progression of disease, up to 2 years. ]
    Progression free survival of nanaliposomal irinotecan with continuous low-dose temozolomide in patients with recurrent glioblastoma.


Secondary Outcome Measures :
  1. Toxicities [ Time Frame: Baseline through 30 days post off study treatment ]
    Toxicities of nanoliposomal irinotecan with continuous low-dose temozolomide using CTCAE version 4.03.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed glioblastoma multiforme (gliosarcoma also eligible), Pathology report to be sent to BrUOG.
  • Progression or recurrence after at least one line of therapy. Patient must have received temozolomide and radiation but it is not required that they were given concurrently.
  • Age >18 years
  • Karnofsky performance score > 60
  • Life expectancy >12 weeks as noted by treating investigator
  • Laboratory results requirements

    • Absolute neutrophil count (ANC) ≥ 1500/mm3.
    • Platelets (Plt) ≥ 100,000/mm3
    • Hemoglobin (Hgb) ≥ 9.0 g/dL
    • Total bilirubin < 1x ULN
    • Albumin levels ≥ 3.0 g/dL
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
    • Serum creatinine ≤ 1.5 x ULN
  • Not pregnant and not nursing. Women of child bearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to Day 1 of treatment. Post-menopausal women (surgical menopause or lack of menses >12 months) do not need to have a pregnancy test, please document status.
  • Confirmation of informed consent.
  • Men and women of childbearing potential enrolled in this study must agree to use adequate barrier birth control measures during the course of the study and for at least 2 months after the last treatment on study.
  • Recovered (< grade 1) from clinically significant effects of any prior surgery, radiotherapy or other anti-neoplastic therapy, except alopecia or hematological laboratory values
  • Stable corticosteroid dose at least 7 days prior to day 1
  • Patients must have assessable (measurable) disease at baseline by brain MRI. Must be contrast enhancing. The tumor size will be measured in millimeters and is the largest cross-sectional area using perpendicular measurements of contrast enhancing abnormality.
  • Patient must be able to tolerate brain MRI with contrast

Exclusion Criteria:

  • Non-GBM primary invasive malignant neoplasm that is considered by treating investigator to likely cause death in the next 5 years.
  • Radiation therapy or cytotoxic chemotherapy or biologics or immunotherapy within previous three weeks from day 1 of drug (no anticancer treatment of any kind within 3 weeks of day 1 of drug- steroids are acceptable if stable dose per 3.1.11).
  • Patients not to be receiving any cancer therapy or investigational anti-cancer drug.
  • Evidence of an active infection requiring intravenous antibiotic therapy
  • Any medical condition that in the opinion of the Investigator may interfere with a subject's participation in or compliance with the study. Must receive confirmation in writing from treating MD.
  • Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment based on serum pregnancy test.
  • Unwillingness or inability to follow the procedures required in the protocol, site to have documentation to confirm at time of registration that this is not the case.
  • Patient with a history of Gilbert's disease or known UGT1A1*28 allele. (Assessment for the UGT1A1*28 allele is not required for protocol entry.) Documentation required at time of study entry by treating MD.
  • myocardial infarction, unstable angina pectoris, stroke within 6 months of study registration.
  • NYHA Class III or IV congestive heart failure
  • Known hypersensitivity to any of the components of nanoliposomal irinotecan , other liposomal products, or temozolomide. Must be documented by treating MD.
  • Investigational anticancer therapy administered within 4 weeks of day 1, or within a time interval less than at least 5 half lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study. Site must submit all prior investigational agents with last dose administered and half-life for BrUOG review.
  • Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed. All recent vaccines (within 30 days) to be listed on conmed log and submitted to BrUOG.
  • Use of strong CYP3A4 inducers is not allowed and patients must be off any of these exclusionary products for > 2 weeks from day 1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03119064


Locations
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United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Kayla Rosati    401-863-3000    kayla_rosati@brown.edu   
Principal Investigator: Heinrich Elinzano, MD         
Sponsors and Collaborators
Heinrich Elinzano, MD
Merrimack Pharmaceuticals
Rhode Island Hospital

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Responsible Party: Heinrich Elinzano, MD, Principal Investigator, Brown University
ClinicalTrials.gov Identifier: NCT03119064     History of Changes
Other Study ID Numbers: BrUOG 329
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: January 7, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Irinotecan
Temozolomide
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents