Recurrent GlioblastomaPhase 2NCT03430791
Trial of Combination Tumor Treating Fields (TTF; Optune), Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma
A Phase 2 study testing Nivolumab 240 mg IV, Nivolumab 3 mg/kg and Ipilimumab 1 mg/kg in people with Recurrent Glioblastoma, run by Baptist Health South Florida at 1 site in United States.
Trial summary
Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioblastoma
- What is being tested?
- Nivolumab 240 mg IV, Nivolumab 3 mg/kg and Ipilimumab 1 mg/kg
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2018to 27 Jan 2021
- Phase
- Phase 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 World Health Organization Grade IV glioblastoma with supratentorial distribution.
- Unequivocal evidence of progressive disease on contrast-enhanced brain CT or MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria, or documented recurrent glioblastoma on biopsy.
- Measurable disease based on RANO criteria.
- Prior therapies including radiation and temozolomide.
- Any number of recurrences are allowed. Resection of recurrent glioblastoma is not considered a prior treatment.
- From the projected start date of study treatment, the following periods must have elapsed: 4 weeks from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), or 4 weeks from any other antibodies or any other antineoplastic therapies.
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- Must be at least 12 weeks from radiotherapy or progression outside of the high-dose radiation target volume or unequivocal evidence of progressive tumor on biopsy.
- All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia.
- Karnofsky Performance Status (KPS) ≥ 60
- Adequate organ and marrow function as defined below, all screening labs should be performed within 14 days of treatment initiation:
- absolute neutrophil count ≥ 1,000/mcL
- platelets ≥100,000/mcL
- hemoglobin > 8.0 mg/dL
- total bilirubin ≤ 2.0 x upper limit of normal
- AST (SGOT)/ALT (SGPT) ≤ 2.5 × upper limit of normal
- creatinine or creatinine clearance ≥ 60 mL/min/1.73 m2 for creatinine >ULN
- Corticosteroid dose must be stable or decreasing for at least 5 days prior to enrollment.
- Nivolumab and ipilimumab are potentially teratogenic or abortifacient. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to entry and for the duration of study. 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. Male subjects should agree to use adequate method of contraception starting with the first dose through 7 months after the last dose of therapy.
- Brain CT or MRI within 14 days prior to start of study drug.
- Archival tissue for evaluation of correlative objectives (if available).
- Ability to understand and the willingness to provide written informed consent.
Who cannot join
- Infratentorial disease.
- Bevacizumab within 2 months of enrollment. Prior use of ipilimumab or other CTLA-4 inhibitor or prior TTFields.
- Tumors with known IDH1 (isocitrate dehydrogenase 1) or IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing. IDH1/2-mutant gliomas have a prolonged overall survival rate compared to IDH1/2-wildtype gliomas, indicating distinct natural history.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or ipilimumab or their excipients.
- Current or planned participation in a study of an investigational agent or using an investigational device.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
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- Active or life-threatening infection requiring intravenous or >2 weeks of systemic therapy.
- Prior stereotactic radiotherapy, convection enhanced delivery (CED) or brachytherapy requires a biopsy to confirm radiographic progression is consistent with progressive tumor and not treatment-related necrosis unless the recurrent lesion is outside of any prior high-dose radiation target volume or distant from the prior CED or brachytherapy site.
- There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, so breastfeeding must be discontinued by enrollment on study.
- Uncontrolled HIV or AIDS is not allowed. Patients with known history of HIV but with undetectable viral load on antiretroviral therapy are allowed.
- Congestive heart failure, myocardial infarction, or hemorrhagic/ischemic stroke in the last 3 months.
- Active illicit drug use or diagnosis of alcoholism
- Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer or other in situ malignancy that has undergone potentially curative therapy and/or with >90% probability of survival beyond 5 years.
- Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of start of treatment. Incomplete recovery from any side effects of previous procedures is also exclusionary.
- Any significant autoimmune disorders expected to impact multiple or internal organs, excluding mild eczema or autoimmune thyroiditis treated with thyroidectomy and requiring systemic immunosuppressive or immunomodulatory therapy.
- Any implanted programmable cranial device, including reprogrammable ventriculoperitoneal shunt (VPS) or cochlear implants, that precludes use of TTFields (Optune) therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida, 33176
About this study
Official title: A Phase I/II Trial of Combination Tumor Treating Fields, Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma
Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.
Read the detailed description
Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.
The NovoTTF200A (OptuneTM) device is worn continuously for a goal of 75% or more of the time, ranging from at least 18 hours daily uninterrupted or 22 hours daily with 2-3 days off monthly. Therapy is planned for approximately 24 months.
Infusions with nivolumab will start within 1 week of study start. Ipilimumab will either start with the second nivolumab infusion or at after tumor progression. Nivolumab is infused intravenously at 240 mg once every 2 weeks with or without ipilimumab for a maximum of 24 months. Ipilimumab is dosed at 1 mg/kg once every 6 weeks for a maximum of 4 doses (24 weeks). Infusions will continue until maximum doses are completed or there is confirmed tumor progression, intolerable adverse effects or withdrawal of consent.
- Conditions
- Recurrent Glioblastoma
- Being tested
- Nivolumab 240 mg IV, Nivolumab 3 mg/kg, Ipilimumab 1 mg/kg, NovoTTF200A (Optune)
- Keywords
- recurrent glioblastoma
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab 240 mg IVDrug
Also called Nivolumab Monotherapy
Nivolumab IV 240mg IV every 2 weeks for maximum of 24 months.
Nivolumab 3 mg/kgDrug
Also called Nivolumab+Ipilimumab
Nivolumab IV 3mg/kg every 2 weeks for maximum of 24 months.
Ipilimumab 1 mg/kgDrug
Also called Nivolumab+Ipilimumab
Ipilimumab IV 1 mg/kg every 6 weeks for maximum of 4 doses.
NovoTTF200A (Optune)Device
A device to be worn continuously for a goal of 75% of the time, ranging from 18 hours daily nonstop or 22 hours daily with 2-3 days off monthly.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab Monotherapy | Experimental | Nivolumab 240 mg IV every 2 weeks for maximum of 24 months. TTF (Optune) for max of 24 months Receives: Drug: Nivolumab 240 mg IV; Device: NovoTTF200A (Optune) |
| Nivolumab+Ipilimumab | Experimental | Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months.
Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months Receives: Drug: Nivolumab 240 mg IV; Drug: Nivolumab 3 mg/kg; Drug: Ipilimumab 1 mg/kg; Device: NovoTTF200A (Optune) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate According to Modified iRANO Criteria
Objective response rate is the proportion of patients whose best overall response per modified immunotherapy response assessment in neuro-oncology (iRANO) criteria is complete (CR) or partial (PR) after at least 6 weeks from start of therapy
Measured: 2 years
Secondary outcomes (7)
Objective Response Rate (ORR) by Standard RANO Criteria
Objective response rate is the proportion of patients whose best overall response per response assessment in neuro-oncology (RANO) criteria is complete (CR) or partial (PR) after at least 6 weeks from start of therapy
Measured: 2 years
Progression Free Survival (PFS)
The length of time that a participant lives with the disease but it does not get worse.
Measured: 2 years
Number of Toxicities
Total number of toxicities as defined by AEs that attributed as probable or possibly related to the study drug across all study subjects.
Measured: Up to 2 years
Rate of Treatment Compliance
Percent of participants who have a compliance rate above the 75% goal for tumor treating fields (TTFields) therapy via the NovoTTF200A (OptuneTM). Daily compliance rates for using the device are averaged (mean ± stdev) over the 28-31 days of the month.
Measured: Monthly for up to 2 years
Discontinuation Rate of Any Component of Therapy
Proportion of participants who discontinued therapy. Reasons for discontinuation also will be noted.
Measured: Up to 2 years
Change in Quality of Life From Baseline Using the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-Br is a validated self-report tool measuring general quality of life (QOL) that assesses symptoms or problems associated with CNS tumors across 5 scales. FACT-Br yields data about total QOL, as well as dimensions of disease specific physical, social/family, emotional, and functional well-being. The tool contains 20 items using a 5-point Likert scale. A higher score indicates better QOL, ranging from 0 (lowest) to 92 (highest). Median percent change between first and last measurement provided, with negative percent change indicating a decline in function.
Measured: Up to 2 years
Change in Quality of Life From Baseline Using the Functional Assessment of Cancer Therapy-General (FACT-G)
FACT-G is a validated self-report tool measuring general quality of life (QOL) that assesses symptoms or problems associated with any tumors. The tool contains 33 items using a 5-point Likert scale. A higher score indicates better QOL, ranging from 0 (lowest) to 108 (highest). Median percent change between first and last measurement provided, with negative percent change indicating a decline in function.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2018
- Study start5 Dec 2018
- Primary completion29 May 2020
- Study completion27 Jan 2021
Why it stopped: Study Investigator/Sponsor decided to end enrollment earlier.
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.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is an open-label, phase II trial with two parallel arms, two-stage design and appropriate stopping rules for poor efficacy. Arm A will enroll participants without prior PD1/PDL1 checkpoint inhibitor, while Arm B will enroll participants with prior PD1/PDL1 checkpoint inhibitor. The investigator expect to enroll at least 30 (15 in each Arm) and a maximum of 60 (30 in each Arm) evaluable subjects. All subjects will receive tumor treating field (TTF) therapy plus nivolumab infusions for a maximum of 24 months, plus/minus concurrent ipilimumab for a maximum of 4 doses.
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baptist Health South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, NovoCure Ltd.
- Responsible party
- Sponsor
- Investigators
- Yazmin Odia, Principal investigator, Miami Cancer Institute at Baptist Health, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03430791
- Sponsor's protocol ID
- 2017-ODI-002
- Status last verified
- Nov 2022
- First submitted
- 31 Jan 2018
- Last updated
- 2 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Combination Tumor Treating Fields, Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT03430791
- Acronym / sponsor ID
- 2017-ODI-002
- Conditions
- Recurrent Glioblastoma
- Keywords
- recurrent glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study Investigator/Sponsor decided to end enrollment earlier.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Baptist Health South FloridaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, NovoCure Ltd.
- Study start
- 5 Dec 2018 (actual)
- Primary completion
- 29 May 2020 (actual)
- Study completion
- 27 Jan 2021 (actual)
- First posted
- 13 Feb 2018 (actual)
- Results
- Posted 2 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.
Detailed description
Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.
The NovoTTF200A (OptuneTM) device is worn continuously for a goal of 75% or more of the time, ranging from at least 18 hours daily uninterrupted or 22 hours daily with 2-3 days off monthly. Therapy is planned for approximately 24 months.
Infusions with nivolumab will start within 1 week of study start. Ipilimumab will either start with the second nivolumab infusion or at after tumor progression. Nivolumab is infused intravenously at 240 mg once every 2 weeks with or without ipilimumab for a maximum of 24 months. Ipilimumab is dosed at 1 mg/kg once every 6 weeks for a maximum of 4 doses (24 weeks). Infusions will continue until maximum doses are completed or there is confirmed tumor progression, intolerable adverse effects or withdrawal of consent.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is an open-label, phase II trial with two parallel arms, two-stage design and appropriate stopping rules for poor efficacy. Arm A will enroll participants without prior PD1/PDL1 checkpoint inhibitor, while Arm B will enroll participants with prior PD1/PDL1 checkpoint inhibitor. The investigator expect to enroll at least 30 (15 in each Arm) and a maximum of 60 (30 in each Arm) evaluable subjects. All subjects will receive tumor treating field (TTF) therapy plus nivolumab infusions for a maximum of 24 months, plus/minus concurrent ipilimumab for a maximum of 4 doses.
| Arm | Type | Receives |
|---|---|---|
| Nivolumab Monotherapy | Experimental | Drug: Nivolumab 240 mg IV, Device: NovoTTF200A (Optune)Nivolumab 240 mg IV every 2 weeks for maximum of 24 months. TTF (Optune) for max of 24 months |
| Nivolumab+Ipilimumab | Experimental | Drug: Nivolumab 240 mg IV, Drug: Nivolumab 3 mg/kg, Drug: Ipilimumab 1 mg/kg, Device: NovoTTF200A (Optune)Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically confirmed World Health Organization Grade IV glioblastoma with supratentorial distribution.
- Unequivocal evidence of progressive disease on contrast-enhanced brain CT or MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria, or documented recurrent glioblastoma on biopsy.
- Measurable disease based on RANO criteria.
- Prior therapies including radiation and temozolomide.
- Any number of recurrences are allowed. Resection of recurrent glioblastoma is not considered a prior treatment.
Key exclusion criteria (16 listed)
- Infratentorial disease.
- Bevacizumab within 2 months of enrollment. Prior use of ipilimumab or other CTLA-4 inhibitor or prior TTFields.
- Tumors with known IDH1 (isocitrate dehydrogenase 1) or IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing. IDH1/2-mutant gliomas have a prolonged overall survival rate compared to IDH1/2-wildtype gliomas, indicating distinct natural history.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or ipilimumab or their excipients.
- Current or planned participation in a study of an investigational agent or using an investigational device.
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 |
|---|---|---|
| Nivolumab 240 mg IVAlso: Nivolumab MonotherapyNivolumab IV 240mg IV every 2 weeks for maximum of 24 months. | Drug | Nivolumab Monotherapy, Nivolumab+Ipilimumab |
| Nivolumab 3 mg/kgAlso: Nivolumab+IpilimumabNivolumab IV 3mg/kg every 2 weeks for maximum of 24 months. | Drug | Nivolumab+Ipilimumab |
| Ipilimumab 1 mg/kgAlso: Nivolumab+IpilimumabIpilimumab IV 1 mg/kg every 6 weeks for maximum of 4 doses. | Drug | Nivolumab+Ipilimumab |
| NovoTTF200A (Optune)A device to be worn continuously for a goal of 75% of the time, ranging from 18 hours daily nonstop or 22 hours daily with 2-3 days off monthly. | Device | Nivolumab Monotherapy, Nivolumab+Ipilimumab |
Primary outcome
Objective Response Rate According to Modified iRANO Criteria
Time frame: 2 years
Objective response rate is the proportion of patients whose best overall response per modified immunotherapy response assessment in neuro-oncology (iRANO) criteria is complete (CR) or partial (PR) after at least 6 weeks from start of therapy
7 secondary outcomes
Objective Response Rate (ORR) by Standard RANO Criteria
Time frame: 2 years
Progression Free Survival (PFS)
Time frame: 2 years
Number of Toxicities
Time frame: Up to 2 years
Rate of Treatment Compliance
Time frame: Monthly for up to 2 years
Discontinuation Rate of Any Component of Therapy
Time frame: Up to 2 years
Change in Quality of Life From Baseline Using the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
Time frame: Up to 2 years
Change in Quality of Life From Baseline Using the Functional Assessment of Cancer Therapy-General (FACT-G)
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Miami Cancer Institute websiteLink provided by the sponsor.
- 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.
Yazmin Odia principal investigator
Miami Cancer Institute at Baptist Health, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab 240 mg IV, Nivolumab 3 mg/kg and Ipilimumab 1 mg/kg in people with Recurrent Glioblastoma, run by Baptist Health South Florida 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 21 inclusion and 16 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 2 Feb 2023. 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 phase mean?
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 2 Feb 2023). 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?
Objective Response Rate According to Modified iRANO Criteria (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Feb 2023.