Glioblastoma
Conditions
Keywords
Glioblastoma
Brief 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
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.
Interventions
DRUGTemozolomide
Temozolomide causes cell death and shrinks and kills the cancer cells
DRUGBavituximab
Bavituximab may activate (cause) the immune system to attack the cancer cells
RADIATIONRadiation
Radiation causes cell death and shrinks and kills the cancer cells.
Sponsors
Peregrine Pharmaceuticals
National Comprehensive Cancer Network
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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
Exclusion criteria
* 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. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at 12 Months (OS12) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Response Rate | every 3 months for 5 years | 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. |
| Progression Free Survival (PFS) | every 3 months for up to 5 years | 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. |
| Overall Survival (OS) | Up to 5 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bavituximab + Standard of Care Radiation + Temozolomide 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. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Clinical progression prior to start of study treatment | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Bavituximab + Standard of Care Radiation + Temozolomide |
|---|---|
| Age, Continuous | 59 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 29 / 36 |
| other Total, other adverse events | 33 / 36 |
| serious Total, serious adverse events | 9 / 36 |
Outcome results
Primary
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.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bavituximab + Standard of Care Radiation + Temozolomide | Overall Survival at 12 Months (OS12) | 72.7 percentage of participants |
Secondary
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.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bavituximab + Standard of Care Radiation + Temozolomide | Overall Survival (OS) | 15.4 months |
Secondary
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.
Time frame: every 3 months for up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bavituximab + Standard of Care Radiation + Temozolomide | Progression Free Survival (PFS) | 6.9 months |
Secondary
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.
Time frame: every 3 months for 5 years
Population: Out of 33 patients, 26 patients had measurable disease at baseline per RANO criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bavituximab + Standard of Care Radiation + Temozolomide | Radiographic Response Rate | 4 Participants |