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

Primary Purpose

Multiple Brain Metastases

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BMX-001
Whole Brain Radiation Therapy
Sponsored by
BioMimetix JV, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Brain Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • 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)

Sites / Locations

  • University of KentuckyRecruiting
  • Henry Ford HospitalRecruiting
  • Duke Cancer InstituteRecruiting
  • University of WashingtonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

WBRT + BMX-001

Whole Brain Radiation Therapy

Arm Description

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).

Whole brain radiation therapy per standard of care.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Compare survival in WBRT + BMX-001 vs WBRT alone
Survival
Compare local recurrence rate in WBRT + BMX-001 vs WBRT alone
Median time to local brain failure or progression
Compare distant brain failure rate in WBRT + BMX-001 vs WBRT alone
Median time to distant brain failure
Compare rate of neurologic death in WBRT + BMX-001 vs WBRT alone
Proportion of patients who are dead within 1 year of initiation of WBRT due to neurologic disease and/or disseminated leptomeningeal carcinomatosis.

Full Information

First Posted
June 14, 2018
Last Updated
February 15, 2023
Sponsor
BioMimetix JV, LLC
Collaborators
Duke Cancer Institute, National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03608020
Brief Title
A Trial for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy
Official Title
A Safety Lead-In/Randomized Phase 2 Study of BMX-001 as a Therapeutic Agent for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 4, 2018 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMimetix JV, LLC
Collaborators
Duke Cancer Institute, National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
This protocol is for a Phase 1 safety lead-in clinical trial of BMX-001 in combination with WBRT in 5 patients with MBM. Demonstrating safety of the selected MTD of BMX-001 in patients with MBM undergoing standard protocol WBRT will be the "go/no-go" criteria for proceeding to Phase 2. Phase 2 is a randomized open-label Phase 2 clinical trial of 64 patients with MBM, half receiving BMX-001 in combination with WBRT and half receiving WBRT alone. Subjects are treated with BMX-001 for a total of 19 days, during which time they receive radiation therapy. Following completion of radiation therapy, subjects will be followed for an additional one year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Brain Metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
69 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
WBRT + BMX-001
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Whole Brain Radiation Therapy
Arm Type
No Intervention
Arm Description
Whole brain radiation therapy per standard of care.
Intervention Type
Drug
Intervention Name(s)
BMX-001
Other Intervention Name(s)
Whole Brain Radiation Therapy
Intervention Description
Manganese butoxyethyl pyridyl porphyrin
Intervention Type
Radiation
Intervention Name(s)
Whole Brain Radiation Therapy
Intervention Description
Whole Brain Radiation Therapy per standard of care.
Primary Outcome Measure Information:
Title
Assess safety and tolerability of WBRT + BMX-001 through proportion of patients who experience grade 4 or 5 study drug related adverse events.
Description
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.
Time Frame
1 year
Title
Compare neurocognition in WBRT + BMX-001 vs. WBRT alone using cumulative score of HVLT-R, TMT A&B and COWA over time.
Description
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.
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Compare survival in WBRT + BMX-001 vs WBRT alone
Description
Survival
Time Frame
1 Year
Title
Compare local recurrence rate in WBRT + BMX-001 vs WBRT alone
Description
Median time to local brain failure or progression
Time Frame
1 Year
Title
Compare distant brain failure rate in WBRT + BMX-001 vs WBRT alone
Description
Median time to distant brain failure
Time Frame
1 Year
Title
Compare rate of neurologic death in WBRT + BMX-001 vs WBRT alone
Description
Proportion of patients who are dead within 1 year of initiation of WBRT due to neurologic disease and/or disseminated leptomeningeal carcinomatosis.
Time Frame
1 Year
Other Pre-specified Outcome Measures:
Title
Compare rate of radionecrosis in WBRT + BMX-001 vs WBRT alone
Description
Proportion of patients with enlarged and/or symptomatic brain lesions with no viable tumor on biopsy
Time Frame
1 Year
Title
Compare QoL in WBRT + BMX-001 vs WBRT alone
Description
Mean change from baseline at each follow-up assessment
Time Frame
1 Year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sara Penchev
Phone
303-862-7268
Email
contact@bmxpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Kirkpatrick, MD
Organizational Affiliation
Duke Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40506
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Judy Guinn
Phone
859-323-2368
Email
Judy.Guinn@uky.edu
First Name & Middle Initial & Last Name & Degree
John Villano, MD
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meghan Gauronskas
Phone
313-916-8827
Email
mgauron1@hfhs.org
First Name & Middle Initial & Last Name & Degree
Tobias Walbert, MD
Facility Name
Duke Cancer Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Franklin, RN
Email
heather.mccullough@duke.edu
First Name & Middle Initial & Last Name & Degree
John Kirkpatrick, MD
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erica Peters
Phone
206-598-7188
Email
etucker@uw.edu
First Name & Middle Initial & Last Name & Degree
Lia Halasz, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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