TerminatedNCT03119064329Updated Dec 13, 2022Results posted

BrUOG 329 Onivyde & Metronomic Temozolomide in Recurrent Glioblastoma

A Phase 1/2 interventional study of Nanoliposomal Irinotecan and Temozolomide in Glioblastoma Multiforme, Glioblastoma and GBM, sponsored by Brown University. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-12-13.

Sponsored by Brown University · Phase 1/2, Interventional, and Treatment

Why this study was terminated

lack of response to study therapy

Phase: Phase 1/2
Study type: Interventional
Enrollment: 12
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the detailed description

1.1 Primary Objective 1.1.1. To evaluate the maximum tolerated dose of nanoliposomal irinotecan with continuous low-dose temozolomide for patients with recurrent glioblastoma.

1.1.2 To assess the preliminary response rate and progression free survival of nanaliposomal irinotecan with continuous low-dose temozolomide in patients with recurrent glioblastoma.

1.2 Secondary Objectives 1.2.1 To evaluate the safety of nanoliposomal irinotecan with continuous low-dose temozolomide.

Conditions studied

Glioblastoma Multiforme
Glioblastoma
GBM

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Glioblastoma 1,951

In context

Glioblastoma

1,951 studies on the registry are indexed under Glioblastoma; 457 are open to participants now.

This study's enrollment of 12 is below the median of 36 across 1,645 interventional studies indexed under Glioblastoma.

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Lead sponsor

Brown University is the lead sponsor of 288 studies on the registry; 38 are open to participants now.

Of its 26 completed or terminated interventional studies of FDA-regulated products, 19 (73%) have results posted.

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Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 12 participants (actual)

Study arms

Experimental
Dose 1
Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 1 50mg/m2 IV every 2 weeks
Drug: Nanoliposomal Irinotecan · Drug: Temozolomide
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 · Drug: Temozolomide
Experimental
Dose 3
Temozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 3 80mg/m2 IV every 2 weeks
Drug: Nanoliposomal Irinotecan · Drug: Temozolomide

Interventions

DrugNanoliposomal 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.
Also known as: Onivyde
DrugTemozolomide
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

What researchers measure

Primary outcomes

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

Secondary outcomes

Toxicities
Treatment emergent toxicities of nanoliposomal irinotecan with continuous low-dose temozolomide using CTCAE version 4.03, grades 2 through 4
Time frame: Baseline through 30 days post off study treatment

Results

Posted Feb 24, 2022

Participant flow

Participant flow — Overall Study
Milestone	Dose 1	Dose 2
Started	9	3
Completed	9	3
Not completed	0	0

Outcome measures

PrimaryDetermination of Maximum Tolerated Dose (MTD)

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

Time frame:: Every two weeks for 4 weeks
Reported as:: Number · mg/m^2

Determination of Maximum Tolerated Dose (MTD)
mg/m^2	All Participants
Determination of Maximum Tolerated Dose (MTD)	50

PrimaryResponse

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."

Time frame:: Every 2 months on study treatment then very 3 months once treatment has stopped, until progression of disease up to 2 years.
Reported as:: Number · participants

Response
participants	Dose 1	Dose 2
Partial Response	1	1
Progressive Disease	8	2

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

Time frame:: Collected every 3 months once treatment has stopped, until progression of disease, up to 2 years.
Reported as:: Count of participants · Participants

Survival Status of Participants Treated With Nanaliposomal Irinotecan With Continuous Low-dose Temozolomide in Patients With Recurrent Glioblastoma.
Participants	Dose 1	Dose 2
Deceased	8	2
Alive	1	1

SecondaryToxicities

Treatment emergent toxicities of nanoliposomal irinotecan with continuous low-dose temozolomide using CTCAE version 4.03, grades 2 through 4

Time frame:: Baseline through 30 days post off study treatment
Reported as:: Number · events

Toxicities
events	Dose 1	Dose 2
Neutropenia	0	1
ALT/AST	2	1
Hypokalemia	1	1
Hypophosphatemia	1	0
Nausea	1	2
Fatigue	2	2
Diarrhea	0	2
Anorexia	0	2
Dehydration	0	2
Urticaria	1	0

Adverse events

Collected over From time of study consent until 30 days after the last dose of study treatment, an average of 6 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Dose 1	8/9 (88.9%)	4/9 (44.4%)	9/9 (100%)
Dose 2	2/3 (66.7%)	3/3 (100%)	3/3 (100%)

Most frequent serious events

Showing 10 of 11

Most frequent serious events
Event	Dose 1	Dose 2
FallInjury, poisoning and procedural complications	1/9	1/3
CraniotomySurgical and medical procedures	3/9	0/3
Muscle weakness right-sidedNervous system disorders	0/9	1/3
C.diffInfections and infestations	0/9	1/3
Thromboembolic eventVascular disorders	2/9	0/3
AspirationRespiratory, thoracic and mediastinal disorders	1/9	0/3
Cerebral edemaNervous system disorders	1/9	0/3
FractureInjury, poisoning and procedural complications	1/9	0/3
Intracranial hemorrhageNervous system disorders	1/9	0/3
Acute pneumoniaRespiratory, thoracic and mediastinal disorders	1/9	0/3

Most frequent other events

Showing 10 of 37

Most frequent other events
Event	Dose 1	Dose 2
DiarrheaGastrointestinal disorders	5/9	2/3
FallInjury, poisoning and procedural complications	1/9	2/3
FatigueGeneral disorders	3/9	2/3
Generalized muscle weaknessMusculoskeletal and connective tissue disorders	1/9	2/3
AnemiaBlood and lymphatic system disorders	3/9	2/3
HypertensionVascular disorders	2/9	2/3
HypoalbuminemiaMetabolism and nutrition disorders	2/9	2/3
HypokalemiaMetabolism and nutrition disorders	3/9	2/3
Lymphocyte count decreasedInvestigations	2/9	2/3
NauseaGastrointestinal disorders	2/9	2/3

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Dose 1	Dose 2	Total
<=18 years	0	0	0
Between 18 and 65 years	7	2	9
>=65 years	2	1	3

Age, Continuous
Age, Continuous(years)	Dose 1	Dose 2	Total
Mean	54 (39 to 70)	64 (58 to 71)	56 (39 to 71)

Sex: Female, Male
Sex: Female, Male(Participants)	Dose 1	Dose 2	Total
Female	1	1	2
Male	8	2	10

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Dose 1	Dose 2	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	0	1
White	8	3	11
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Dose 1	Dose 2	Total
United States	9	3	12

Study locations

1 site

Rhode Island Hospital
Providence, Rhode Island 02903, United States

References and documents

Publications

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. PubMed 33284237 ↗

Study documents

Protocol, analysis plan and consent form · Dec 8, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Nov 2017 to primary completion in Apr 2020, 28 months.

Results were first posted in Feb 2022, 1 year 10 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Apr 6, 2017
First posted: Apr 18, 2017
StartActual: Nov 30, 2017
Primary completionActual: Apr 10, 2020
CompletionActual: Oct 8, 2021
Results first posted: Feb 24, 2022
Last update: Dec 13, 2022

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Dec 13, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03119064
Lead sponsor: Brown University
Collaborators: Merrimack Pharmaceuticals, Rhode Island Hospital
Responsible party: Sponsor
First posted: Apr 18, 2017
Start date: Nov 30, 2017
Primary completion: Apr 10, 2020
Completion: Oct 8, 2021
Results posted: Feb 24, 2022
Last update: Dec 13, 2022

Study contacts

Howard Safran, MD

study chair · BrUOG Study Chair

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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