BrUOG 329 Onivyde & Metronomic Temozolomide in Recurrent Glioblastoma

NCT03119064 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: BrUOG 329
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma Multiforme; Glioblastoma; GBM

Outcome Measures

Primary Outcomes (3)

• Determination of Maximum Tolerated Dose (MTD)

  To evaluate the maximum tolerated dose of nanoliposomal irinotecan with continuous low-dose temozolomide for patients with recurrent glioblastoma.

  Every two weeks for 4 weeks

• Response

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."

  Every 2 months on study treatment then very 3 months once treatment has stopped, until progression of disease up to 2 years.

• Survival Status of Participants Treated With Nanaliposomal Irinotecan With Continuous Low-dose Temozolomide in Patients With Recurrent Glioblastoma.

  Collected every 3 months once treatment has stopped, until progression of disease, up to 2 years.

Secondary Outcomes (1)

• Toxicities

  Baseline through 30 days post off study treatment

Study Arms (3)

Dose 1

EXPERIMENTAL

Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 1 50mg/m2 IV every 2 weeks

Drug: Nanoliposomal Irinotecan; Drug: Temozolomide

Dose 2

EXPERIMENTAL

Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks

Drug: Nanoliposomal Irinotecan; Drug: Temozolomide

Dose 3

EXPERIMENTAL

Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 3 80mg/m2 IV every 2 weeks

Drug: Nanoliposomal Irinotecan; Drug: Temozolomide

Interventions

Nanoliposomal Irinotecan DRUG

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.

Also known as: Onivyde

Dose 1; Dose 2; Dose 3

Temozolomide DRUG

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.

Also known as: TMZ

Dose 1; Dose 2; Dose 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brown University: lead
• Merrimack Pharmaceuticals: collaborator
• Rhode Island Hospital: collaborator

Study Sites (1)

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Related Publications (1)

• Elinzano H, Toms S, Robison J, Mohler A, Carcieri A, Cielo D, Donnelly J, Disano D, Vatketich J, Baekey J, Sturtevant A, MacKinnon K, Wood R, Safran H. Nanoliposomal Irinotecan and Metronomic Temozolomide for Patients With Recurrent Glioblastoma: BrUOG329, A Phase I Brown University Oncology Research Group Trial. Am J Clin Oncol. 2021 Feb 1;44(2):49-52. doi: 10.1097/COC.0000000000000780.

  PMID: 33284237 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

irinotecan sucrosofate; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Heinrich Elinzano, MD
• Organization: Brown University Oncology Research Group

BrUOG@BROWN.EDU

401-863-3000

Study Officials

• Howard Safran, MD

  BrUOG Study Chair

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 18, 2017
• Study Start: November 30, 2017
• Primary Completion: April 10, 2020
• Study Completion: October 8, 2021
• Last Updated: December 13, 2022
• Results First Posted: February 24, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)