Glioma, Recurrent Glioblastoma, Recurrent Glioma
Conditions
Brief summary
This clinical trial tests how well a digital treatment platform using a mobile application works for the delivery of home-based sequential therapy in patients with glioma. Access to specialized neuro-oncology care in the United States for patients with glioma is critically deficient. Care at centers with neuro-oncology specialists is associated with improved survival outcomes, yet many patients have limited access due to distance, disease-related disability, or lack of financial resources. The application provides patients continuous access to their care team in the home setting. A digital treatment platform may increase clinical trial participation and accelerate development of novel therapeutics while addressing a great health disparity in patients with glioma.
Detailed description
PRIMARY OBJECTIVES: I. Determine the feasibility of the remote chemotherapy management and patient monitoring platform glioma home-based sequential therapy (GHoST) protocol among patients with glioma undergoing systemic therapy. II. Determine the efficacy, as measured by the 4-month progression free survival (PFS) rate, of propranolol and imipramine, when used in combination with bevacizumab for the treatment of recurrent glioblastoma. (Subprotocol 1: PRIME) SECONDARY OBJECTIVES: I. Evaluate compliance, adherence, and feasibility in terms of the adherence to systemic therapy monitored remotely. II. Determine progression free survival (PFS) for each therapeutic evaluated for newly diagnosed or recurrent glioma, stratified by tumor type. III. Determine objective response rate (ORR) for each therapeutic evaluated for newly diagnosed or recurrent glioma, stratified by tumor type. IV. Assess the safety and tolerability of remote chemotherapy management and patient monitoring among patients with glioma undergoing systemic therapy. V. Determine overall survival (OS) for each therapeutic evaluated for recurrent glioblastoma when used in combination with bevacizumab. (Subprotocol 1: PRIME) VI. Determine objective response rate (ORR) for each therapeutic evaluated for recurrent glioblastoma when used in combination with bevacizumab. (Subprotocol 1: PRIME) VII. Assess the safety and tolerability for each therapeutic evaluated for recurrent glioblastoma when used in combination with bevacizumab. (Subprotocol 1: PRIME) EXPLORATORY OBJECTIVES: I. Assess the acceptance or satisfaction of patients with the remote monitoring in this trial and how these may differ between newly diagnosed and recurrent glioma. II. Investigate PFS based on therapeutic sequence administered. III. Explore potential differences in compliance, adherence, and satisfaction measures and how they may correspond to health disparities and social determinants of health. IV. Compare access to neuro-oncology care at Mayo Clinic among patients with low socioeconomic status assessed based on the Mayo Clinic Housing-Based Socioeconomic Status (HOUSES) Index during the two years following study activation compared to historical utilization data. V. Compare access to neuro-oncology care at Mayo Clinic among patients with increased distance from academic centers assessed by geospatial index during the two years following study activation compared to historical utilization data. OUTLINE: GHoST MASTER PROTOCOL: Patients receive access to the remote chemotherapy management and patient monitoring platform to watch educational videos, report when medication is taken or missed, and report any symptoms related to cancer or medication side effects on study. Patients also receive standard of care chemotherapy as assigned by their treating physician as part of the platform on study. Upon completion of standard of care chemotherapy, if there is no disease progression, patients transition to surveillance for up to 1 year. Patients who experience disease progression during treatment or surveillance may rejoin the platform and/or be assigned by their treating physician to a different chemotherapy agent as part of the platform. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) throughout the study. SUBPROTOCOL 1 - PRIME: Patients with recurrent glioblastoma receiving bevacizumab on the GHoST Master Protocol as assigned by their treating physician are randomized to 1 of 2 groups. GROUP A: Patients receive propranolol orally (PO) twice daily (BID) and standard of care (SOC) bevacizumab intravenously (IV) every 3 weeks of each cycle. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the study. GROUP B: Patients receive imipramine PO once daily (QD) and SOC bevacizumab IV every 3 weeks of each cycle. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the study.
Interventions
DRUGChemotherapy
Receive standard of care chemotherapy
PROCEDUREComputed Tomography
Undergo CT
OTHERInternet-Based Intervention
Receive access to the remote chemotherapy management and patient monitoring platform
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDURENeurologic Examination
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
BEHAVIORALSurveillance
Undergo surveillance
DRUGPropranolol
Given PO
DRUGImipramine
Given PO
DRUGBevacizumab
Given IV
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosis of glioma and intention to treat with either new or ongoing systemic therapy for at least 6 months. * NOTE: Patient may be enrolled following completion of surgery and/or radiation therapy for newly diagnosed or recurrent tumor. * NOTE: Any number of prior recurrences is permitted * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, AND Karnofsky performance status (KPS) of ≥ 60 * Expected survival ≥ 6 months in the opinion of treatment team * Willing and able to adhere with the protocol for the duration of the study including undergoing treatment, and attending scheduled visits, and examinations * Negative pregnancy test ≤ 8 days prior to registration for persons of childbearing potential only * Exception: Not required if patient is already on treatment. May be obtained prior to next treatment as needed per clinical care * Provide written informed consent * Ability to complete assessments and questionnaires by themselves or with assistance * SUBSTUDY 1: Enrolled in GHoST Master Protocol per eligibility criteria of the master study and clinically appropriate to proceed with bevacizumab treatment at the discretion of the treating physician * SUBSTUDY 1: Diagnosis of recurrent glioblastoma and intention to treat with bevacizumab * NOTE: Any number of prior recurrences is permitted * NOTE: Prior limited use of bevacizumab for radiation necrosis/treatment related edema is permitted. Prior use should not exceed four infusions with the last dose administered ≥ 4 weeks prior to enrollment in this substudy * SUBSTUDY 1: Willing and able to adhere to the substudy for the duration of the substudy including undergoing treatment, and attending scheduled visits, and examinations * SUBSTUDY 1: Negative pregnancy test ≤ 8 days prior to registration for persons of childbearing potential only * SUBSTUDY 1: Provide written informed consent * SUBSTUDY 1: Ability to complete assessments and questionnaires by themselves or with assistance
Exclusion criteria
* Pregnant or nursing, imprisoned, or lacking capacity for understanding * Uncontrolled and/or intercurrent illness or other condition which limits safety of or compliance with study proceedings * SUBSTUDY 1: Pregnant or nursing, imprisoned, or lacking capacity for understanding * SUBSTUDY 1: Uncontrolled and/or intercurrent illness or other condition which limits safety of or compliance with study proceedings
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility - completion of study visits | At baseline and the set of study-specific visits through 6 months (i.e., 26 weeks ± 2 weeks) | Feasibility will be assessed by the number of study visits completed vs. not. Will consider this to be feasible in this patient population if the true compliance rate is at least 60%. Compliance here is defined as completion of at least 4 disease assessment timepoints in the first 6 months on study (i.e. 26 ± 2 weeks). These assessment timepoints will include the baseline assessment and can include assessments after 2 cycles of therapy, after 4 cycles of therapy, after 6 cycles of therapy, dependent on the treatment-specific schedules. |
| 4-month progression-free survival (PFS) rate (Subprotocol 1) | Up to 4 months after beginning study therapy | Defined as the number of patients who are alive and progression-free at least 4 months after beginning study therapy. A point estimate will be generated for 4-month PFS rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acceptance of and satisfaction of patients with the remote monitoring | Up to 3 years | Will be assessed with an electronic Assessment of Acceptance and Satisfaction survey sent to participants at study assessment timepoints. The satisfaction survey consists of a single question answered on a 5-point scale: very positive, somewhat positive, neutral, somewhat negative, very negative. |
| Adherence to study therapeutics | Up to 3 years | Will be assessed through remote monitoring application. Here, adherence is defined as taking at least 80% of the prescribed doses, for all therapies other than lomustine. For lomustine, adherence is defined as receiving all prescribed infusions. |
| Feasibility of remote systemic therapy assessments | Up to 3 years | Will be assessed through completion of visits as scheduled, where laboratory and imaging assessed for the visits are scheduled and completed prior to telehealth visits. Feasibility will be defined as having necessary pre-visit testing completed and delivered for clinician review prior to the visit as well as completion of the visit at the intended scheduled time for 60% of the visits. |
| Progression free survival (PFS) for each therapeutic treatment diagnosed and recurrent glioma | At 6 months | Will be assessed for each treatment evaluated. PFS is defined as the time from enrollment to disease progression or death, whichever occurs first. |
| Objective response rate | Up to 3 years | Objective response rate for each therapeutic for newly diagnosed and recurrent glioma will be assessed. |
| Incidence of adverse events | Up to 3 years | Will be assessed by type along with grade and perceived attribution to study agent based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
| Safety of the overall platform | Up to 3 years | Will be assessed by acute care utilization days (defined as emergency department evaluations and inpatient days) for participants on the platform compared to historical clinical data. |
| Overall survival (OS) from initiation of study treatment (Subprotocol 1) | Up to 3 years | Defined as the time from initiation of study treatment and survival time from initial diagnosis. |
| Objective response rate (ORR) (Subprotocol 1) | Up to 3 years | Defined as the time from initiation of study treatment and survival time from initial diagnosis. Will be assessed per Response Assessment in Neuro-Oncology (RANO) Criteria 2.0 |
| Incidence of adverse events (Subprotocol 1) | Up to 3 years | Will be assessed by type along with grade and perceived attribution to study agent based on NCI CTCAE version 5. |
Countries
United States
Contacts
CONTACTClinical Trials Referral Office
CONTACTCancer Center Clinical Trials
PRINCIPAL_INVESTIGATORUgur T. Sener, MD
Mayo Clinic in Rochester
Outcome results
None listed