Phase II Clinical Trial of Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma
Overview
- Phase
- Phase 2
- Intervention
- Temozolomide
- Conditions
- Glioblastoma
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 36
- Locations
- 2
- Primary Endpoint
- Overall Survival at 12 Months (OS12)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Elizabeth R. Gerstner, MD
Principle Investigator
Massachusetts General Hospital
Eligibility Criteria
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
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
Arms & Interventions
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.
Intervention: Temozolomide
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.
Intervention: Bavituximab
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.
Intervention: Radiation
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Radiographic Response Rate(every 3 months for 5 years)
- Progression Free Survival (PFS)(every 3 months for up to 5 years)
- Overall Survival (OS)(Up to 5 years)