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Manganese

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.

BMX-001

Whole Brain Radiation Therapy per standard of care.

Whole Brain Radiation Therapy

John Kirkpatrick, MD

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.

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.

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

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

Proportion of patients with enlarged and/or symptomatic brain lesions with no viable tumor on biopsy

Mean change from baseline at each follow-up assessment

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.

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.

Median time to local brain failure or progression

Proportion of patients who are dead within 1 year of initiation of WBRT due to neurologic disease and/or disseminated leptomeningeal carcinomatosis.

Duke Cancer Institute

National Cancer Institute (NCI)

BioMimetix JV, LLC

Neoplasms, Second Primary

Antineoplastic Agents

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Group A: multiple brain metastases: no less than 3 lesions in the brain Group B: Large Brain Metastases: the volume of lesion is no smaller than 6cc or the maximum diameter of the lesion is no shorter than 3cm Group C:Meningeal Metastases

The regular fraction modes were as follows: a. lesions≥3 cm：52Gy/4Gy/13f or 52.5Gy/3.5Gy/15f; b. lesions\<2cm：36Gy/12Gy/3f or 24Gy/24Gy/1f; for lesions located in function areas, it would be adjusted to 40Gy/8Gy/5f; c. lesions 2-3cm：40-48Gy/8-10Gy/6-4f; d. lesions located in brainstem：50-60Gy/2.5-3Gy/20f.

Fractionated Stereotactic Radiotherapy

concomitant TMZ: 75mg/m2 adjuvant TMZ: 150mg/m2\*5d, q28d, 6cycles

Jianping Xiao

This clinical trial was designed to investigate the efficiency and toxicity of fractionated stereotactic radiotherapy(FSRT) combined with Temozolomide(TMZ) for refractory brain metastases.

This is a single-arm, single center, phase II trial to investigate the feasibility and toxicity of FSRT plus TMZ for refractory brain metastases, which are defined as A: multiple brain metastases(≥3 lesions); B: large brain metastases(with one lesion's volume is no smaller than 6cc or the longest diameter is no shorter than 3cm); C: meningeal metastases.

Stereotactic Radiotherapy Plus Temozolomide for Refractory Brain Metastases

Fractionated Stereotactic Radiotherapy Combined With Temozolomide for Refractory Brain Metastases: A Single-arm, Single-center Phase II Trial

defined as no progress of the treated lesions and no distant progress in the brain

Using RTOG9508 criteria, Tumor control is defined as CR+PR+SD

assessed by CTCAE criteria, v4.0 and RTOG criteria of the central nervous system

collect the data of causes of death and analyze

Cancer Foundation, China

Chinese Academy of Medical Sciences

Group A: multiple brain metastases: no less than 3 lesions in the brain Group B: Large Brain Metastases: the volume of lesion is no smaller than 6cc or the maximum diameter of the lesion is no shorter than 3cm Group C:Meningeal Metastases.

Intervention：tomotherapy

Tomotherapy: The regular fraction modes were as follows: a. lesions≥3 cm:52Gy/4Gy/13f or 52.5Gy/3.5Gy/15f; b. lesions\<2cm:36Gy/12Gy/3f or 24Gy/24Gy/1f; for lesions located in function areas, it would be adjusted to 40Gy/8Gy/5f; c. lesions 2-3cm: 40-48Gy/8-10Gy/6-4f; d. lesions located in brainstem:50-60Gy/2.5-3Gy/20f; 3. multiple lesions with large lesion: whole brain radiation (WBRT) with 40Gy/2Gy/20f and concurrent boost of 60Gy/3Gy/20f of the lesions.

TMZ is used if necessary: concomitant TMZ: 75mg/m2 adjuvant TMZ: 150mg/ m2\*5d, q28d, up to 6cycles.

tomotherapy

This clinical trial was designed to investigate the efficiency and toxicity of tomotherapy for refractory brain metastases.

This is a single-arm, single center, phase II trial to investigate the feasibility and toxicity of tomotherapy for refractory brain metastases, which are defined as A: multiple brain metastases(≥3 lesions); B: large brain metastases(with one lesion's volume is no smaller than 6cc or the longest diameter is no shorter than 3cm); C: meningeal metastases.

Tomotherapy for Refractory Brain Metastases

Tomotherapy for Refractory Brain Metastases: a Single Arm, Single Center Phase II Trial

the baseline characteristics and treatment plan can be shared with other researchers when the research paper has been published. The IPD will be sent by email if applied.

patients with multiple brain metastases (no less than 3 lesions) ,who have not recived whole brain radiotheray (WBRT).

Whole brain radiation (WBRT) with 38-40Gy in 20 fractions and concurrent boost of 60-70Gy of the lesions. TMZ is used if necessary: concomitant TMZ: 75mg/m2 adjuvant TMZ: 150mg/ m2\*5d, q28d, up to 6cycles.

This clinical trial was designed to investigate the efficiency and toxicity of tomotherapy as primary radiotherapy for multiple brain metastases.

This is a single-arm, single center, phase II trial to investigate the feasibility and toxicity of tomotherapy as primary radiotherapy for multiple brain metastases(≥3 lesions).

Tomotherapy as Primary Radiotherapy for Multipule Brain Metastases

Tomotherapy as Primary Radiotherapy for Multipule Brain Metastases:A Single Arm, Single Center,Phase II Trial

Using RTOG9508 criteria, tumor control is defined as CR+PR+SD

the time from radiation to any progression

the time from radiation to the treated brain metastases recurrence

the time from radiation to local recurrence and/or new brain metastases

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Selected 224 patients with multiple brain metastases from NSCLC, they will be randomized to WBRT or Erotinib concurrent WBRT. It was enough to compare the efficacy of Erotinib concurrent WBRT vs. WBRT

Erlotinib

WBRT

1. Verify the effect of Erlotinib concurrent whole-brain radiation therapy as ﬁrst-line treatment for patients with multiple brain metastases from non-small-cell lung cancer to compare with WBRT alone.
2. Verify pre-built EGFR mutation prediction model for NSCLC brain metastases

All patients will be randomized to receive WBRT or Erlotinib concurrent WBRT. Erlotinib concurrent WBRT, patients were given a loading dose of erlotinib 150mg per day for 6 days, after which all patients received erlotinib 150mg per day concurrently with WBRT. Dose reduction was allowed for intolerable adverse effects (grade ≥3) such as rash or diarrhea in 50 mg increments down from 150mg to 100 mg and then to 50 mg if needed. Radiation therapy was delivered in 2.0 Gy fractions once per day 5 days per week to a total dose of 40Gy (20 fractions). Radiation was delivered as opposed lateral 8-MV beams with a Sweden precise linear accelerator.

Phase Ⅲ Trial of WBRT Versus Erlotinib Concurrent Whole-brain Radiation Therapy as ﬁrst-line Treatment for Patients With Multiple Brain Metastases From Non-small-cell Lung Cancer(ENTER): a Multicentre, Open-label, Randomised Study

1. Focal EGFR 1 certification pre built NSCLC mutation prediction model of brain metastasis.
2. Blood sample was collected for patients with Erotinib biomarker research.

A) assess the local control of brain metastases status (including: the proportion of salvage therapy, the proportion of radiation necrosis lesions)

B) evaluation of intracranial metastasis status (at the site of the primary tumor than the emergence of new brain metastases)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy	NCT03608020	Multiple Brain ...	BMX-001 Whole Brain Rad...	18 Years -	BioMimetix JV, LLC
Stereotactic Radiotherapy Plus Temozolomide for Refractory Brain Metastases	NCT02654106	Brain Metastase...	Fractionated St... Temozolomide	18 Years - 75 Years	ChineseAMS
Tomotherapy for Refractory Brain Metastases	NCT03027544	Brain Metastase...	tomotherapy	18 Years - 75 Years	ChineseAMS
Tomotherapy as Primary Radiotherapy for Multipule Brain Metastases	NCT04178330	Brain Metastase...	tomotherapy	18 Years - 75 Years	ChineseAMS
Tomotherapy as Primary Radiotherapy for Multipule Brain Metastases	NCT04178330	Brain Metastase...	tomotherapy	18 Years - 75 Years	ChineseAMS
Stereotactic Radiotherapy Plus Temozolomide for Refractory Brain Metastases	NCT02654106	Brain Metastase...	Fractionated St... Temozolomide	18 Years - 75 Years	ChineseAMS
Phase Ⅲ Trial of WBRT Versus Erlotinib Concurrent Whole-brain Radiation Therapy as ﬁrst-line Treatment for Patients With Multiple Brain Metastases From Non-small-cell Lung Cancer(ENTER): a Multicentre, Open-label, Randomised Study	NCT01887795	Multiple Brain ... Non-small-cell ...	Erlotinib WBRT	18 Years -	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Phase Ⅲ Trial of WBRT Versus Erlotinib Concurrent Whole-brain Radiation Therapy as ﬁrst-line Treatment for Patients With Multiple Brain Metastases From Non-small-cell Lung Cancer(ENTER): a Multicentre, Open-label, Randomised Study	NCT01887795	Multiple Brain ... Non-small-cell ...	Erlotinib WBRT	18 Years -	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
A Trial for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy	NCT03608020	Multiple Brain ...	BMX-001 Whole Brain Rad...	18 Years -	BioMimetix JV, LLC
Tomotherapy for Refractory Brain Metastases	NCT03027544	Brain Metastase...	tomotherapy	18 Years - 75 Years	ChineseAMS

Spots Global Cancer Trial Database for multiple brain metastases