Glioblastoma MultiformePhase 1/2329NCT03119064
BrUOG 329 Onivyde & Metronomic Temozolomide in Recurrent Glioblastoma
A Phase 1/2 study testing Nanoliposomal Irinotecan and Temozolomide in people with Glioblastoma Multiforme and Glioblastoma, run by Brown University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Glioblastoma, GBM
- What is being tested?
- Nanoliposomal Irinotecan and Temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2017to 8 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rhode Island Hospital
Providence, Rhode Island, 02903
About this study
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
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
- Glioblastoma Multiforme, Glioblastoma, GBM
- Being tested
- Nanoliposomal Irinotecan, Temozolomide
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nanoliposomal IrinotecanDrug
Also called Onivyde
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.
TemozolomideDrug
Also called TMZ
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose 1 | Experimental | Temozolomide: 50mg/m2/day until disease progression.
Nanoliposomal irinotecan :
Dose Level 1 50mg/m2 IV every 2 weeks Receives: 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 Receives: 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 Receives: Drug: Nanoliposomal Irinotecan; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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."
Measured: 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.
Measured: Collected every 3 months once treatment has stopped, until progression of disease, up to 2 years.
Secondary outcomes (1)
Toxicities
Treatment emergent toxicities of nanoliposomal irinotecan with continuous low-dose temozolomide using CTCAE version 4.03, grades 2 through 4
Measured: Baseline through 30 days post off study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study start30 Nov 2017
- Primary completion10 Apr 2020
- Study completion8 Oct 2021
Why it stopped: lack of response to study therapy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- Merrimack Pharmaceuticals, Rhode Island Hospital
- Responsible party
- Sponsor
- Investigators
- Howard Safran, MD, Study chair, BrUOG Study Chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03119064
- Sponsor's protocol ID
- BrUOG 329
- Acronym
- 329
- Status last verified
- Nov 2022
- First submitted
- 6 Apr 2017
- Last updated
- 13 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 at a glance
From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03119064
- Acronym / sponsor ID
- 329 / BrUOG 329
- Conditions
- Glioblastoma Multiforme, Glioblastoma, GBM
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of response to study therapy
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- Merrimack Pharmaceuticals, Rhode Island Hospital
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- 10 Apr 2020 (actual)
- Study completion
- 8 Oct 2021 (actual)
- First posted
- 18 Apr 2017 (actual)
- Results
- Posted 24 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose 1 | Experimental | Drug: Nanoliposomal Irinotecan, Drug: TemozolomideTemozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 1 50mg/m2 IV every 2 weeks |
| Dose 2 | Experimental | Drug: Nanoliposomal Irinotecan, Drug: TemozolomideTemozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 2 70 mg/m2 IV every 2 weeks |
| Dose 3 | Experimental | Drug: Nanoliposomal Irinotecan, Drug: TemozolomideTemozolomide: 50mg/m2/day until disease progression. Nanoliposomal irinotecan : Dose Level 3 80mg/m2 IV every 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nanoliposomal IrinotecanAlso: OnivydeThree 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. | Drug | Dose 1, Dose 2, Dose 3 |
| TemozolomideAlso: TMZThree 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. | Drug | Dose 1, Dose 2, Dose 3 |
Primary outcome
Determination of Maximum Tolerated Dose (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.
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.
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."
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.
1 secondary outcome
Toxicities
Time frame: Baseline through 30 days post off study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33284237Elinzano 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Howard Safran, MD study chair
BrUOG Study Chair
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nanoliposomal Irinotecan and Temozolomide in people with Glioblastoma Multiforme and Glioblastoma, run by Brown University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of Maximum Tolerated Dose (MTD) (time frame: Every two weeks for 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03119064, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2022.