Clinical trial NCT03861598: Carvedilol With Chemotherapy in Second Line Glioblastoma and Response of Circulating Tumor Cells
Official title: A Feasibility Study: Evaluating Carvedilol With Chemotherapy in Second Line Glioblastoma Multiforme and Response of Peripheral Glioma Circulating Tumor Cells
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Glioblastoma Multiforme
Glioblastoma
Lead sponsor: West Virginia University
Sponsor class: OTHER
Collaborators: name: West Virginia Clinical and Translational Science Institute
First posted: 2019-03-04
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Subjects will receive standard chemotherapy and Tumor Treated Fields (TTFields) and will also receive Carvedilol for 4 cycles of treatment. Carvedilol will start at 6.25 mg orally twice a day and be increased to 12.5 mg orally twice daily after 1 to 2 weeks if tolerated. Peripheral glioma circulating tumor cells (CTC) and brain MRI with and without contrast will be obtained at baseline, 2 cycles, and 4 cycles to determine the efficacy and direction of change of the CTC using a new assay tool. Preliminary assessment of the tolerability of Carvedilol with standard chemotherapy will also be evaluated.

Detailed description: This will be a feasibility study to assess the use of a new PCR assay with response to standard chemotherapy treatment in the second line setting in glioblastoma multiforme (GBM). The change in direction with the combination of carvedilol with standard of chemotherapy based upon brain MRI results will be assessed and associating that with also the change in the quantity of tumor cells with a new invented assay device. Six subjects will be enrolled in the study who have recurrent GBM and will be receiving second line treatment.

The subjects will receive standard therapy per the discretion of the treating oncologist. Carvedilol will start at 6.25 mg orally twice daily for 1-2 weeks to confirm tolerance. The subjects will then receive carvedilol at 12.5 mg orally twice daily as the maximum dose and take it continuously for 4 cycles of therapy. At the completion of 4 cycles, patients will stop taking carvedilol. If the patients were on previous anti-hypertensive medications, they will be instructed to restart those medications if stopped on this trial for carvedilol.

Peripheral blood samples will be collected at baseline before initiation of treatment, on first day of every cycle for four cycles and after the last cycle is completed to obtain peripheral glioma circulating tumor levels. Subjects will be re-evaluated for response every 2 cycles of therapy with brain MRI with and without contrast.

Eligibility criteria: Inclusion Criteria:

* Grade IV Glioblastoma, receiving chemotherapy with or without TTfields.
* Progressive or recurrent disease requiring second line treatment
* evidence of progression of disease by brain MRI and are planned to receive chemotherapy

Exclusion Criteria:

* Current use of another beta blocker that cannot be switched to carvedilol at the onset of the trial.
* Systolic blood pressure \<90 mmHg and/or heart rate \<60 bpm without hypertensive medications
* Allergy to beta blockers
* Severe or uncontrolled asthma or COPD (chronic obstructive pulmonary disease)

Primary outcomes:
measure: Identify the correlation between our new RT-qPCR assay for circulating tumor cells and the change in responses in patients on treatment to MRI results.
timeFrame: Baseline, end of cycle 2, end of cycle 4, approximately 6 months depending on treatment plan
Secondary outcomes:
measure: Evaluate response with the addition of carvedilol to standard chemotherapy in the second line treatment in glioblastoma multiforme
timeFrame: Baseline, end of cycle 2, end of cycle 4, approximately 6 months depending on treatment plan
measure: Evaluate incidents of adverse events during the time subjects are taking carvedilol with chemotherapy
timeFrame: From Baseline to 30 days after stopping carvedilol.
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: WVU Cancer Institute - Mary Babb Randolph Cancer Center
state: West Virginia
Study officials:
affiliation: West Virginia University
name: Joanna Kolodney, MD
role: PRINCIPAL_INVESTIGATOR
References: