GlioblastomaPhase 2NCT03139916
Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma
A Phase 2 study testing Temozolomide, Bavituximab and Radiation in people with Glioblastoma, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
This research study is studying a combination of drugs with radiation as a possible treatment for Glioblastoma. The drugs involved in this study are: Bavituximab Temozolomide Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Temozolomide, Bavituximab and Radiation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Sep 2017to 31 Aug 2022
- 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
- Participants must have histologically confirmed newly diagnosed glioblastoma or glioblastoma variant (ex. gliosarcoma), including documentation of unmutated isocitrate dehydrogenase (IDH) by immunohistochemistry (sequencing not required).
- Participants must have 1-4 cm2 measurable disease (4 cm2 is the maximal size). See Section 11 for the evaluation of measurable disease. Disseminated GBM is not allowed.
- No prior immunotherapy allowed or prior alkylating agents or prior radiation to the brain.
- Age >17 years since adult GBM is biologically different from pediatric GBM and there is no data for bavituximab in pediatric populations.
- Karnofsky ≥60%, see Appendix A
- Life expectancy of greater than 6 months.
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- Participants must have normal organ and marrow function as defined below:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin within normal institutional limits (unless patient has Gilbert's syndrome in which total bilirubin should be ≤ 2xULN)
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- creatinine within normal institutional limits OR
- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal(using Cockcroft Gault Formula)
- negative serum pregnancy test in WOCBP
- INR/PT ≤1.5 x institutional ULN unless subject is receiving anticoagulant therapy as long as PT or INR is within therapeutic range of intended use of anticoagulants
- aPTT ≤1.5 x institutional ULN unless subject is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants
- < 4 mg dexamethasone daily (or equivalent if on another corticosteroid) at time of start of therapy. Patients on a steroid taper post-surgery and are anticipated to be on <4 mg at time of chemoradiation initiation will be eligible to consent but to initiate treatment on trial, the participant must be on <4 mg or equivalent of steroids otherwise participate will be deemed a screen fail and be replaced.
- The effects of bavituximab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of bavituximab administration.
- Able to undergo an MRI scan and receive gadolinium-based contrast.
- 1 cm3 of available tissue.
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Participants who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to bavituximab.
- Participants receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of bavituximab. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product (Appendix C for partial list).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because bavituximab is an immunotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bavituximab breastfeeding should be discontinued if the mother is treated with bavituximab. These potential risks may also apply to other agents used in this study.
- HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with bavituximab. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
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- Participants with other active malignancy in the past 3 years excluding in situ tumors.
- Participants must meet the following windows from procedures (there is no window required for port placement since there is no anticipated impact on wound healing with bavituximab):
- Major surgery (ex. craniotomy) within 3 weeks of initiation of treatment.
- Brain biopsy within 2 weeks
- Participants with history of bleeding disorder/coagulopathy.
- Participants with history of chronic or acute hepatitis C or B infection
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Massachusetts general Hospital
Boston, Massachusetts, 02115
About this study
Official title: Phase II Clinical Trial of Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma
This research study is studying a combination of drugs with radiation as a possible treatment for Glioblastoma.
The drugs involved in this study are:
- Bavituximab
- Temozolomide
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Bavituximab as a treatment for any disease.
The FDA has approved Temozolomide as a treatment option for this disease.
In this research study, the investigators are studying how the combination of Bavituximab, Temozolomide, and radiation affects this cancer. The current standard care of treatment for newly diagnosed glioblastoma is the combination of Temozolomide and radiation. Temozolomide causes cell death and radiation shrinks and kills the cancer cells. Bavituximab may activate (cause) the immune system to attack the cancer cells as well as target tumor cells themselves to kill them.
- Conditions
- Glioblastoma
- Being tested
- Temozolomide, Bavituximab, Radiation
- Keywords
- Glioblastoma
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodar
Temozolomide causes cell death and shrinks and kills the cancer cells
BavituximabDrug
Bavituximab may activate (cause) the immune system to attack the cancer cells
RadiationRadiation
Radiation causes cell death and shrinks and kills the cancer cells.
| Study group | Role | What they receive |
|---|---|---|
| Bavituximab + Standard of Care Radiation + Temozolomide | Experimental | Cycle 1 consists of 6 weeks (42 days) of chemoradiation. Radiation therapy is administered per standard of care. Bavituxumab 3 mg/kg IV administration starts during the 1st week of chemoradiation and continues weekly. Temozolomide 75/m2 is administered orally once daily.
Cycle 2 is 4 weeks (28 days) long and Bavituxumab 3 mg/kg IV administration occurs weekly.
Cycle 3 and beyond are each 4 weeks (28 days) long. Bavituxumab 3 mg/kg IV administration occurs weekly for a cumulative total of 18 weeks; treatment may continue beyond 18 weeks at the discretion of the treating physician if the participant is deriving clinical benefit. Temozolomide 150-200 mg/m2 is administered orally once daily on days 1-5 in cycles 3 and 4. Receives: Drug: Temozolomide; Drug: Bavituximab; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival at 12 Months (OS12)
Overall survival is defined as the time from study entry to death from any cause. OS12 is the percentage of subjects who are alive 12 months after study entry. Data for subjects who are lost to follow up prior to documented death will be counted as deaths at the last assessment date when the subject is known to be alive.
Measured: 12 months
Secondary outcomes (3)
Radiographic Response Rate
Radiographic response (RR) is defined as a complete response or partial response per RANO (Response assessment in neuro-oncology) criteria with incorporation of iRANO (immunotherapy response assessment for neuro-oncology) criteria. The radiographic response rate is the percentage of subjects who achieved radiographic response as defined above.
Measured: every 3 months for 5 years
Progression Free Survival (PFS)
Progression free survival is defined as the time of study entry to time of disease progression, or death due to any cause. Data for subjects who are lost to follow up will be censored at the date when the subject is last known to be alive. PFS results below are reported up to the data cutoff in May 2021.
Measured: every 3 months for up to 5 years
Overall Survival (OS)
Overall survival is defined as the time of study entry to death from any cause. Data for subjects who are lost to follow up will be censored at the date when the subject is last known to be alive. OS results below are reported up to the data cutoff in May 2021.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start13 Sep 2017
- Primary completion31 Aug 2022
- Study completion31 Aug 2022
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 GlioblastomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Peregrine Pharmaceuticals, National Comprehensive Cancer Network
- Responsible party
- Principal investigator, Elizabeth R. Gerstner, MD, Massachusetts General Hospital
- Investigators
- Elizabeth R Gerstner, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03139916
- Sponsor's protocol ID
- 17-037
- Status last verified
- May 2024
- First submitted
- 2 May 2017
- Last updated
- 16 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ly KI, Richardson LG, Liu M, Muzikansky A, Cardona J, Lou K, Beers AL, Chang K, Brown JM, Ma X, Reardon DA, Arrillaga-Romany IC, Forst DA, Jordan JT, Lee EQ, Dietrich J, Nayak L, Wen PY, Chukwueke U, Giobbie-Hurder A, Choi BD, Batchelor TT, Kalpathy-Cramer J, Curry WT, Gerstner ER. Bavituximab Decreases Immunosuppressive Myeloid-Derived Suppressor Cells in Newly Diagnosed Glioblastoma Patients. Clin Cancer Res. 2023 Aug 15;29(16):3017-3025. doi: 10.1158/1078-0432.CCR-23-0203.
PubMed 37327319
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial of Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT03139916
- Acronym / sponsor ID
- 17-037
- Conditions
- Glioblastoma
- Keywords
- Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Peregrine Pharmaceuticals, National Comprehensive Cancer Network
- Study start
- 13 Sep 2017 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 4 May 2017 (actual)
- Results
- Posted 16 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a combination of drugs with radiation as a possible treatment for Glioblastoma.
The drugs involved in this study are:
- Bavituximab
- Temozolomide
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Bavituximab as a treatment for any disease.
The FDA has approved Temozolomide as a treatment option for this disease.
In this research study, the investigators are studying how the combination of Bavituximab, Temozolomide, and radiation affects this cancer. The current standard care of treatment for newly diagnosed glioblastoma is the combination of Temozolomide and radiation. Temozolomide causes cell death and radiation shrinks and kills the cancer cells. Bavituximab may activate (cause) the immune system to attack the cancer cells as well as target tumor cells themselves to kill them.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bavituximab + Standard of Care Radiation + Temozolomide | Experimental | Drug: Temozolomide, Drug: Bavituximab, Radiation: RadiationCycle 1 consists of 6 weeks (42 days) of chemoradiation. Radiation therapy is administered per standard of care. Bavituxumab 3 mg/kg IV administration starts during the 1st week of chemoradiation and continues weekly. Temozolomide 75/m2 is administered orally once daily. Cycle 2 is 4 weeks (28 days) long and Bavituxumab 3 mg/kg IV administration occurs weekly. Cycle 3 and beyond are each 4 weeks (28 days) long. Bavituxumab 3 mg/kg IV administration occurs weekly for a cumulative total of 18 weeks; treatment may continue beyond 18 weeks at the discretion of the treating physician if the participant is deriving clinical benefit. Temozolomide 150-200 mg/m2 is administered orally once daily on days 1-5 in cycles 3 and 4. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Participants must have histologically confirmed newly diagnosed glioblastoma or glioblastoma variant (ex. gliosarcoma), including documentation of unmutated isocitrate dehydrogenase (IDH) by immunohistochemistry (sequencing not required).
- Participants must have 1-4 cm2 measurable disease (4 cm2 is the maximal size). See Section 11 for the evaluation of measurable disease. Disseminated GBM is not allowed.
- No prior immunotherapy allowed or prior alkylating agents or prior radiation to the brain.
- Age >17 years since adult GBM is biologically different from pediatric GBM and there is no data for bavituximab in pediatric populations.
- Karnofsky ≥60%, see Appendix A
Key exclusion criteria (12 listed)
- Participants who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to bavituximab.
- Participants receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of bavituximab. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product (Appendix C for partial list).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because bavituximab is an immunotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bavituximab breastfeeding should be discontinued if the mother is treated with bavituximab. These potential risks may also apply to other agents used in this study.
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 |
|---|---|---|
| TemozolomideAlso: TemodarTemozolomide causes cell death and shrinks and kills the cancer cells | Drug | Bavituximab + Standard of Care Radiation + Temozolomide |
| BavituximabBavituximab may activate (cause) the immune system to attack the cancer cells | Drug | Bavituximab + Standard of Care Radiation + Temozolomide |
| RadiationRadiation causes cell death and shrinks and kills the cancer cells. | Radiation | Bavituximab + Standard of Care Radiation + Temozolomide |
Primary outcome
Overall Survival at 12 Months (OS12)
Time frame: 12 months
Overall survival is defined as the time from study entry to death from any cause. OS12 is the percentage of subjects who are alive 12 months after study entry. Data for subjects who are lost to follow up prior to documented death will be counted as deaths at the last assessment date when the subject is known to be alive.
3 secondary outcomes
Radiographic Response Rate
Time frame: every 3 months for 5 years
Progression Free Survival (PFS)
Time frame: every 3 months for up to 5 years
Overall Survival (OS)
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37327319Ly KI, Richardson LG, Liu M, Muzikansky A, Cardona J, Lou K, Beers AL, Chang K, Brown JM, Ma X, Reardon DA, Arrillaga-Romany IC, Forst DA, Jordan JT, Lee EQ, Dietrich J, Nayak L, Wen PY, Chukwueke U, Giobbie-Hurder A, Choi BD, Batchelor TT, Kalpathy-Cramer J, Curry WT, Gerstner ER. Bavituximab Decreases Immunosuppressive Myeloid-Derived Suppressor Cells in Newly Diagnosed Glioblastoma Patients. Clin Cancer Res. 2023 Aug 15;29(16):3017-3025. doi: 10.1158/1078-0432.CCR-23-0203.
- 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.
Elizabeth R Gerstner, MD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide, Bavituximab and Radiation in people with Glioblastoma, run by Massachusetts General Hospital at 2 sites 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 22 inclusion and 12 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: finished, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 16 May 2024). 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?
Overall Survival at 12 Months (OS12) (time frame: 12 months). 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 NCT03139916, 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 16 May 2024.