A Trial for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy

NCT03608020 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: BMX-MBM-0011R44CA228694-01
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

This protocol is for a lead-in safety study of 5 patients followed by a randomized Phase 2 clinical trial of BMX-001, a new class of pharmaceutical, in 64 patients with multiple brain metastases (MBM) undergoing whole brain radiation therapy (WBRT). Preliminary studies have demonstrated that BMX-001 provides protection of normal tissues from radiation-induced injury and augments tumor growth inhibition.

Conditions

Multiple Brain Metastases

Outcome Measures

Primary Outcomes (2)

• Assess safety and tolerability of WBRT + BMX-001 through proportion of patients who experience grade 4 or 5 study drug related adverse events.

  AEs will be assessed according to the CTCAE version 5.0. If CTCAE grading does not exist for an AE, the severity of the AE will be graded as mild (1), moderate (2), severe (3), life-threatening (4), or fatal (5). Initially 5 patients will be accrued and treated with WBRT + BMX-001 as a lead-in safety phase. Enrollment to the randomized phase of the study will not proceed if patients in the safety lead-in phase experience the following: * Two or more patients are unable to complete radiation therapy (RT) due to toxicity related to BMX-001 (alone or in combination with RT. * Two or more patients experience delay in starting RT due to toxicity related to BMX-001 (alone or in combination with RT). If any patient experiences a grade 4 or 5 BMX-001-related adverse event within Arm A (WBRT + BMX-001), accrual will be suspended and the experience of the patient will be carefully reviewed by the clinical team and the study's DSMB.

  1 year

• Compare neurocognition in WBRT + BMX-001 vs. WBRT alone using cumulative score of HVLT-R, TMT A&B and COWA over time.

  Subjects will complete three standardized tests (Hopkins Verbal Learning Test - Revised, Trail Making Test A\&B, and Controlled Oral Word Association test) at baseline, 1 month after completion of WBRT and every 3 months after completion of WBRT. The cumulative score of these three tests will be used to assess change.

  1 Year

Secondary Outcomes (4)

• Compare survival in WBRT + BMX-001 vs WBRT alone

  1 Year

• Compare local recurrence rate in WBRT + BMX-001 vs WBRT alone

  1 Year

• Compare distant brain failure rate in WBRT + BMX-001 vs WBRT alone

  1 Year

• Compare rate of neurologic death in WBRT + BMX-001 vs WBRT alone

  1 Year

Other Outcomes (2)

• Compare rate of radionecrosis in WBRT + BMX-001 vs WBRT alone

  1 Year

• Compare QoL in WBRT + BMX-001 vs WBRT alone

  1 Year

Study Arms (2)

WBRT + BMX-001

ACTIVE COMPARATOR

Whole brain radiation therapy in combination with BMX-001 (subcutaneous injection of 28 mg loading dose, followed by subsequent 14 mg twice per week for 2 weeks).

Drug: BMX-001; Radiation: Whole Brain Radiation Therapy

Whole Brain Radiation Therapy

NO INTERVENTION

Whole brain radiation therapy per standard of care.

Interventions

BMX-001 DRUG

Manganese butoxyethyl pyridyl porphyrin

Also known as: Whole Brain Radiation Therapy

WBRT + BMX-001

Whole Brain Radiation Therapy RADIATION

Whole Brain Radiation Therapy per standard of care.

WBRT + BMX-001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically confirmed diagnosis of a non-small cell lung cancer, breast cancer, melanoma or renal cell cancer primary
• Subjects must have \>5 contrast-enhancing lesions, never previously treated with SRS and/or surgical resection, on a contrast-enhanced T1-weighted brain MRI performed within two weeks of enrollment, with at least one lesion \>0.5cm in greatest dimension
• Physical examination by a radiation oncologist or medical oncologist within 14 days of the start of WBRT
• Plan to be treated with WBRT to a dose of 30 Gy in 10 fractions
• Age \* 18 years
• Karnofsky Performance Status (KPS) ≥ 70
• Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/\*l, platelets ≥ 125,000 cells/\*l
• Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of normal
• Signed informed consent approved by the Institutional Review Board
• If sexually active, patients must agree to use appropriate contraceptive measures for the duration of the study and for 6 months afterwards as stated in the informed consent
• Able to provide study specific informed consent
• Willing to follow study procedures, complete QOL questionnaires and neurocognitive testing as described in the protocol
• Negative serum pregnancy test for women of child bearing potential within 48 hours of first dose of BMX

You may not qualify if:

• Active infection requiring IV antibiotics 7 days before enrollment
• Hypertension requiring 3 or more anti-hypertensive medications to control
• Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure
• History of syncope within the last 6 months
• Subjects receiving prohibited medications listed in Section 6.4.2 of this protocol are not eligible. Subjects who can safely stop taking a prohibited medication at least 7 days prior to the first dose of BMX may participate at the discretion of the treating physician.
• Women who are breast feeding
• Known hypersensitivity to compounds of similar chemical composition to BMX-001
• Prior surgical resection for brain metastases and/or stereotactic radiosurgery for up to 5 brain metastases in total are permitted if performed at least 1 month prior to planned WBRT under this protocol.
• Prior whole brain radiation therapy
• Patients with diffuse leptomeningeal disease (carcinomatous meningitis)
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>480 milliseconds (ms) (CTCAE grade 1)
• A history of additional risk factors for TdP (e.g., congestive heart failure, hypokalemia, known family history of Long QT Syndrome)

Sponsors & Collaborators

• BioMimetix JV, LLC: lead
• Duke Cancer Institute: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (4)

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Study Officials

• John Kirkpatrick, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2018
• First Posted: July 31, 2018
• Study Start: October 4, 2018
• Primary Completion: December 31, 2023
• Study Completion: April 15, 2024
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)