Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
BMX-MBM-001
- SECONDARY ID:
1R44CA228694-01
- NCT ID:
NCT03608020
Conditions
- Multiple Brain Metastases
Interventions
Drug | Synonyms | Arms |
---|
BMX-001 | Whole Brain Radiation Therapy | WBRT + BMX-001 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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). | |
Whole Brain Radiation Therapy | No Intervention | Whole brain radiation therapy per standard of care. | |
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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Assess safety and tolerability of WBRT + BMX-001 through proportion of patients who experience grade 4 or 5 study drug related adverse events. |
Time Frame: | 1 year |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Compare survival in WBRT + BMX-001 vs WBRT alone |
Time Frame: | 1 Year |
Safety Issue: | |
Description: | Survival |
Measure: | Compare local recurrence rate in WBRT + BMX-001 vs WBRT alone |
Time Frame: | 1 Year |
Safety Issue: | |
Description: | Median time to local brain failure or progression |
Measure: | Compare distant brain failure rate in WBRT + BMX-001 vs WBRT alone |
Time Frame: | 1 Year |
Safety Issue: | |
Description: | Median time to distant brain failure |
Measure: | Compare rate of neurologic death in WBRT + BMX-001 vs WBRT alone |
Time Frame: | 1 Year |
Safety Issue: | |
Description: | Proportion of patients who are dead within 1 year of initiation of WBRT due to neurologic disease and/or disseminated leptomeningeal carcinomatosis. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | BioMimetix JV, LLC |
Last Updated
February 5, 2021