A Digital Treatment Platform for the Delivery of Home-Based Sequential Therapy in Patients With Glioma, GHoST Trial

MC240703 Neuro-Oncology Anywhere: Glioma Home-Based Sequential Therapy (GHoST) Protocol

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.

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.

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