Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03608020
Recruitment Status : Recruiting
First Posted : July 31, 2018
Last Update Posted : September 9, 2019
Sponsor:
Collaborators:
Duke Cancer Institute
National Cancer Institute (NCI)
Information provided by (Responsible Party):
BioMimetix JV, LLC

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.

Condition or disease Intervention/treatment Phase
Multiple Brain Metastases Drug: BMX-001 Radiation: Whole Brain Radiation Therapy Phase 1 Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 69 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 4, 2018
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : September 30, 2022

Arm Intervention/treatment
Active Comparator: WBRT + BMX-001
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
Manganese butoxyethyl pyridyl porphyrin
Other Name: Whole Brain Radiation Therapy

Radiation: Whole Brain Radiation Therapy
Whole Brain Radiation Therapy per standard of care.

No Intervention: Whole Brain Radiation Therapy
Whole brain radiation therapy per standard of care.



Primary Outcome Measures :
  1. 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 ]

    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.


  2. Compare neurocognition in WBRT + BMX-001 vs. WBRT alone using cumulative score of HVLT-R, TMT A&B and COWA over time. [ Time Frame: 1 Year ]
    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 :
  1. Compare survival in WBRT + BMX-001 vs WBRT alone [ Time Frame: 1 Year ]
    Survival

  2. Compare local recurrence rate in WBRT + BMX-001 vs WBRT alone [ Time Frame: 1 Year ]
    Median time to local brain failure or progression

  3. Compare distant brain failure rate in WBRT + BMX-001 vs WBRT alone [ Time Frame: 1 Year ]
    Median time to distant brain failure

  4. Compare rate of neurologic death in WBRT + BMX-001 vs WBRT alone [ Time Frame: 1 Year ]
    Proportion of patients who are dead within 1 year of initiation of WBRT due to neurologic disease and/or disseminated leptomeningeal carcinomatosis.


Other Outcome Measures:
  1. Compare rate of radionecrosis in WBRT + BMX-001 vs WBRT alone [ Time Frame: 1 Year ]
    Proportion of patients with enlarged and/or symptomatic brain lesions with no viable tumor on biopsy

  2. Compare QoL in WBRT + BMX-001 vs WBRT alone [ Time Frame: 1 Year ]
    Mean change from baseline at each follow-up assessment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 >10 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03608020


Contacts
Layout table for location contacts
Contact: Sara Penchev 720-613-4872 contact@bmxpharma.com

Locations
Layout table for location information
United States, North Carolina
Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Heather Franklin, RN       heather.mccullough@duke.edu   
Principal Investigator: John Kirkpatrick, MD         
Sponsors and Collaborators
BioMimetix JV, LLC
Duke Cancer Institute
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: John Kirkpatrick, MD Duke Cancer Institute

Layout table for additonal information
Responsible Party: BioMimetix JV, LLC
ClinicalTrials.gov Identifier: NCT03608020     History of Changes
Other Study ID Numbers: BMX-MBM-001
1R44CA228694-01 ( U.S. NIH Grant/Contract )
First Posted: July 31, 2018    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases