- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04771897
A Study of BXQ-350 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) or Diffuse Midline Glioma (DMG) (KONQUER)
A Phase 1 Open Label, Multi-Center Study to Evaluate the Safety and Tolerability of BXQ-350 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) and Diffuse Midline Glioma (DMG)
Study Overview
Status
Detailed Description
BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a cell membrane phospholipid (clinical formulation BXQ-350). Given via intravenous IV, data indicate that the agent exhibits the propensity to enter the body and brain, target cells in the tumor mass, and induce cell death. DIPG and DMG present a treatment dilemma due to resistance to standard therapy (radiotherapy) and aggressive clinical course. The use of BXQ-350 provides a novel approach to the treatment of cancer through interaction with the cancer cell membrane. This drug appears to be well tolerated in previous clinical trials, and in combination with the standard of care radiation therapy, may help improve overall survival in these patients.
The study is divided into 2 parts:
Part 1: Dose Escalation and Safety - Sequential cohorts of patients 1-30 years of age with newly diagnosed DIPG or DMG will be treated with escalating doses of BXQ-350 until the MTD is established, or in the absence of a Maximum Administered Dose, the highest planned dose level is reached.
Part 2: BXQ-350 Tumor and Plasma Concentrations - Patients undergoing neurosurgical biopsy prior to receiving radiation therapy will be enrolled and receive BXQ-350 at the MTD determined in Part 1, or at the highest planned dose level, and radiation therapy. Excised tumor tissue will be evaluated for SapC levels and pharmacodynamic effects.
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.)
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Bexion Pharmaceuticals, Inc.
- Phone Number: 1-859-446-7386
- Email: clinicaltrialinfo@bexionpharma.com
Study Locations
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Recruiting
- Children's Hospital Colorado
-
Principal Investigator:
- Kathleen Dorris, MD
-
Contact:
- Kathleen Dorris, MD
- Phone Number: 720-777-5771
- Email: ETPResearch@childrenscolorado.org
-
-
Ohio
-
Cincinnati, Ohio, United States, 45226
- Recruiting
- Cincinnati Children's Hospital Medical Center
-
Principal Investigator:
- Trent Hummel, MD
-
Contact:
- Clinical Trial Office
- Phone Number: 513-636-2799
- Email: cancer@cchmc.org
-
Columbus, Ohio, United States, 43205
- Recruiting
- Nationwide Children's
-
Contact:
- Melinda Triplet, RN
- Phone Number: 614-722-6039
- Email: Melinda.Triplet@nationwidechildrens.org
-
Principal Investigator:
- Maryam Fouladi, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Each subject must meet the following criteria:
- Provide signed, written informed consent prior to the initiation of any study-specific procedures (consent from guardians for minor children and patient assent according to institution and Institutional Review Board (IRB) standards)
- Age ≥ 1 year of age and ≤ 30 years of age at the time of study entry
Have radiographically suspected or histologically confirmed newly diagnosed DIPG or DMG with the following defining disease characteristics/features:
Part 1 and Part 2:
- DIPG: radiographic imaging showing a diffuse expansion of the brainstem/pons by a tumor that is poorly defined but abnormally bright in signal on T2-weighted images and abnormally dark on T1-weighted images; contrast enhancement, when present, is typically mild; there may be some indication of necrosis, and the basilar artery is commonly engulfed by tumor.
- DMG: the same imaging characteristics as noted above for DIPG are present, but the lesion can extend superiorly up into the midbrain and thalami, and/or inferiorly to the medulla.
- In cases of disease that is not classic for DIPG or DMG, biopsy may be necessary in order to obtain histological confirmation of eligibility.
- Part 2: newly-diagnosed DIPG or DMG planning to undergo biopsy at the recommendation of the treating physician; to be considered evaluable for PK tissue concentration analysis, tumor samples must have at least 50% viable tumor cells with <30% necrosis or hemorrhage as determined by the study neuropathologist
- If receiving glucocorticoid therapy: dexamethasone allowed with maximum allowable dose 16mg/day
- Have measurable or non-measurable disease per RANO criteria
Have Lansky (age 1 - 15) / Karnofsky (age ≥ 16) Performance Score of ≥ 50% or Eastern Cooperative Oncology Group (ECOG) Performance Status (age ≥ 18) of 0 - 2
- Subjects unable to walk because of paralysis, but who can sit without assistance/restraint and control a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Have acceptable liver function defined as:
- Total serum bilirubin ≤ 1.5 x upper limit of normal for the study site (ULN) (in subjects with known Gilbert Syndrome, total bilirubin ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN)
- Aspartate Transaminase (AST), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alanine Transaminase (ALT), Serum Glutamic-Pyruvic Transamine (SGPT) ≤ 3 x ULN (if liver metastases are present, then ≤ 5 x ULN is allowed)
- Serum albumin ≥ 3 grams/deciliter (g/dL)
Have acceptable renal function defined as:
Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70 milliliters (mL)/min/1.73 meters squared (m2) or a serum creatinine based on age/gender as follows: 1 to < 2 years: 0.6 (male); 0.6 (female) 2 to < 6 years: 0.8 (male); 0.8 (female) 6 to < 10 years: 1 (male); 1 (female) 10 to < 13 years: 1.2 (male); 1.2 (female) 13 to < 16 years: 1.5 (male); 1.4 (female)
16 years: 1.7 (male);1.4 (female)
- Threshold creatinine values derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (Schwartz 2009)
Have acceptable bone marrow function defined as:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/ cubic millimeter (mm3)
- Platelet count ≥ 100,000 cells/mm3 (unsupported, no transfusion within 7 days of enrollment)
- Hemoglobin > 9.0 g/dL (unsupported, no transfusion within 7 days of enrollment)
Have acceptable coagulation parameters (anti-coagulation allowed) defined as:
- International normalized ratio (INR) ≤ 2 x ULN unless on anticoagulation or prothrombin time (PT) within normal limits
- Activated partial thromboplastin time (aPTT) within normal limits
- Have a negative serum pregnancy test result at screening (for females of child bearing potential (FCBP); not applicable to subjects who are unable to become pregnant, including those with tubal ligation, bilateral oophorectomy and/or hysterectomy, post-menopausal is defined as > 12 months since last menstrual cycle)
- FCBP and male subjects whose sexual partner(s) are FCBP must agree to abstain from heterosexual activity or use a double barrier method of contraception (e.g., condom and occlusive cap with spermicide) or highly effective contraception (intrauterine device or system, established hormonal contraceptive methods on a stable dose from the time of the last menstrual cycle, or vasectomized partner with confirmed azoospermia) from the time of study entry to 1 month after the last day of treatment
Exclusion Criteria:
Subjects must not meet any of the following criteria:
- Have a concurrent or secondary malignancy
- Have a low-grade glioma (Grade II or less)
- Have received prior treatment with radiation, chemotherapy, anti-neoplastic, or investigational agents
- Have had major surgery other than a minor outpatient procedure within 28 days prior to dose assignment or have not recovered from major side effects of the surgery if more than 4 weeks have elapsed since surgery
- Have poorly controlled hypertension despite the use of antihypertensive agents defined as blood pressure ≥95th percentile for age and weight or >160/90 on at least 2 repeated determinations on separate days within 2 weeks (14 days) prior to initiation of screening
Have a history of cardiac dysfunction including:
- myocardial infarction within 6 months prior to initiation of screening
- history of documented congestive heart failure (New York Heart Association functional classification III-IV) within 6 months prior to initiation of screening
- active cardiomyopathy
- electrocardiogram (ECG) with QTc >470 msec at screening
- echocardiogram with ejection fraction <50% or a decrease in the left ventricular shortening fraction to <27%
- Have a known history of Human Immunodeficiency Virus (HIV) seropositivity
- Have active (acute or chronic) or uncontrolled severe infections
- Have active poor wound healing (delayed healing, wound infection or fistula)
- Have evidence of active clinically significant bleed (e.g., gastrointestinal bleed, hemoptysis, or gross hematuria) at screening
- Are pregnant or nursing, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test
- Have a known sensitivity to any component of BXQ-350
- Have other concurrent severe and/or uncontrolled medical condition that would, in the Principal Investigator's judgment contraindicate the subject's participation in the clinical study or obscure assessment of toxicity
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1 Dose Escalation: Safety and Tolerance
Sequential cohorts of patients with newly diagnosed DIPG or DMG will be treated with escalating doses of BXQ-350 until the maximum tolerated dose (MTD) is established, or in the absence of a maximum administered dose (MAD), the highest planned dose level is reached and radiation therapy.
|
BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a phospholipid located on cell membranes (clinical formulation BXQ-350).
During Part 1, BXQ-350 will be administered by intravenous (IV) infusion over twelve months.
Other Names:
|
Experimental: Part 2 BXQ-350 Tumor and Plasma Concentrations
Newly diagnosed DIPG or DMG patients undergoing neurosurgical biopsy prior to receiving radiation therapy will receive BXQ-350 at the MTD established in Part 1, or the highest planned dose level, and radiation therapy.
Excised tumor tissue and plasma samples will be evaluated for SapC levels and pharmacodynamic effects.
|
BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a phospholipid located on cell membranes (clinical formulation BXQ-350).
During Part 2, BXQ-350 will be administered by intravenous (IV) infusion over twelve months.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0
Time Frame: 12 months
|
To determine the safety of BXQ-350 in children with newly diagnosed DIPG or DMG, as evidenced by the incidence of treatment emergent adverse events assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
|
12 months
|
Part 1 - Maximum Tolerated Dose
Time Frame: 12 months
|
To determine the maximum tolerated dose (MTD) of BXQ-350, when given with radiation therapy, according to the investigational product (IP) related dose limiting toxicities (DLTs) in children with newly diagnosed DIPG or DMG.
|
12 months
|
Part 2 - BXQ-350 Concentration in Tumor Samples
Time Frame: 12 months
|
To determine the concentration of BXQ-350 in tumor samples as evidenced by laboratory analysis of excised tumor tissue for SapC levels (a component of BXQ-350).
|
12 months
|
Part 2 - BXQ-350 Concentration in Plasma Samples
Time Frame: 12 months
|
To determine the concentration of BXQ-350 in plasma samples as evidenced by laboratory analysis of plasma samples for SapC levels (a component of BXQ-350).
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: 12 months
|
To determine the ORR of BXQ-350 when given with radiation therapy in children with newly diagnosed DIPG or DMG.
ORR is defined as the percentage of participants with evidence of a complete or partial response as per the Response Assessment in Neuro-Oncology (RANO) criteria.
|
12 months
|
Overall Survival (OS)
Time Frame: 12 months
|
To evaluate OS in children with newly diagnosed DIPG or DMG receiving BXQ-350 with radiation therapy.
OS is defined as the time from initiation of therapy to death from any cause.
Participants still alive will be censored at the date of the last contact.
|
12 months
|
Quality of Life (QoL)
Time Frame: 12 months
|
To evaluate QoL in children with newly diagnosed DIPG or DMG receiving BXQ-350 with radiation therapy.
QoL will be measured utilizing the Patient-Reported Outcomes Measurement Information System (PROMIS) in participants 5 years of age or older.
PROMIS measures use a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation.
A higher score equals more of the concept being measured (i.e. more fatigue, more physical function, etc.).
This could be a desirable or undesirable outcome, depending on the concept being measured.
|
12 months
|
Concentration of drug at steady state (Css)
Time Frame: 12 months
|
To assess exposure to BXQ-350 in children with newly diagnosed DIPG or DMG receiving BXQ-350 with radiation therapy.
Exposure will be measured utilizing pharmacokinetic parameter of concentration of drug at steady state (Css).
|
12 months
|
Exposure to BXQ-350 - area under the curve (AUC)
Time Frame: 12 months
|
To assess exposure to BXQ-350 in children with newly diagnosed DIPG or DMG receiving BXQ-350 with radiation therapy.
Exposure will be measured utilizing pharmacokinetic parameter of area under the curve (AUC).
|
12 months
|
Exposure to BXQ-350 - clearance (CL)
Time Frame: 12 months
|
To assess exposure to BXQ-350 in children with newly diagnosed DIPG or DMG receiving BXQ-350 with radiation therapy.
Exposure will be measured utilizing pharmacokinetic parameter of clearance (CL).
|
12 months
|
Exposure to BXQ-350 - volume of distribution (Vd)
Time Frame: 12 months
|
To assess exposure to BXQ-350 in children with newly diagnosed DIPG or DMG receiving BXQ-350 with radiation therapy.
Exposure will be measured utilizing pharmacokinetic parameter of volume of distribution (Vd).
|
12 months
|
Exposure to BXQ-350 - half-life (t½)
Time Frame: 12 months
|
To assess exposure to BXQ-350 in children with newly diagnosed DIPG or DMG receiving BXQ-350 with radiation therapy.
Exposure will be measured utilizing pharmacokinetic parameter of volume of half-life (t½).
|
12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Brain Neoplasms
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Brain Stem Neoplasms
- Infratentorial Neoplasms
- Glioma
- Diffuse Intrinsic Pontine Glioma
Other Study ID Numbers
- BXQ-350.AD
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diffuse Intrinsic Pontine Glioma
-
National Cancer Institute (NCI)RecruitingRecurrent Malignant Glioma | Recurrent Medulloblastoma | Refractory Malignant Glioma | Refractory Medulloblastoma | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Primary Central Nervous System Neoplasm | Refractory Primary Central Nervous System Neoplasm | Refractory Diffuse Intrinsic Pontine...United States, Canada
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Solving Kids' CancerCompletedDiffuse Intrinsic Pontine Glioma (DIPG)United States
-
University of California, San FranciscoTranslational Genomics Research InstituteCompletedDiffuse Intrinsic Pontine Glioma (DIPG)United States
-
University of California, San FranciscoNational Institute of Neurological Disorders and Stroke (NINDS); The Chad-Tough... and other collaboratorsRecruitingDiffuse Intrinsic Pontine Glioma | Diffuse Midline Glioma, H3 K27M-Mutant | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Diffuse Midline Glioma, H3 K27M-Mutant | Recurrent WHO Grade III Glioma | WHO Grade III GliomaUnited States, Israel, Australia, Netherlands, Switzerland, New Zealand
-
Burzynski Research InstituteSuspendedDiffuse, Intrinsic Pontine GliomaUnited States
-
University of FloridaAccelerate Brain Cancer Cure; Lyla Nsouli FoundationActive, not recruitingBrain Stem Glioma | Diffuse Intrinsic Pontine Glioma (DIPG)United States
-
Shenzhen Geno-Immune Medical InstituteShenzhen Children's Hospital; Shenzhen Hospital of Southern Medical UniversityUnknownDiffuse Intrinsic Pontine Glioma or GlioblastomaChina
-
Hadassah Medical OrganizationCompletedPediatric Malignant Brain Tumor -Diffuse Intrinsic Pontine GliomaIsrael
-
Pediatric Brain Tumor ConsortiumNational Cancer Institute (NCI)CompletedMalignant Glioma | Recurrent Childhood Ependymoma | Recurrent Medulloblastoma | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Atypical Teratoid/Rhabdoid Tumor | Refractory Diffuse Intrinsic Pontine Glioma | CNS Embryonal Tumor, Not Otherwise SpecifiedUnited States
-
Cheng-Chia (Fred) WuFocused Ultrasound FoundationActive, not recruitingDiffuse Intrinsic Pontine Glioma | Diffuse Midline Glioma, H3 K27M-Mutant | Diffuse Pontine and Thalamic GliomasUnited States
Clinical Trials on BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance
-
Domain Therapeutics SARecruitingSolid Tumor, AdultFrance, Belgium
-
Hinova Pharmaceuticals Inc.RecruitingMetastatic Castration-resistant Prostate CancerChina
-
Jiangsu Hansoh Pharmaceutical Co., Ltd.RecruitingCML, Chronic Phase | CML, Accelerated PhaseChina
-
Janssen Research & Development, LLCTerminatedLymphoma, Follicular | Lymphoma, Large B-Cell, Diffuse | Lymphoma, Mantle-Cell | Precursor Cell Lymphoblastic Leukemia-Lymphoma | Leukemia, Lymphocytic, Chronic, B-CellUnited States, France, Spain, Belgium, Israel
-
Kazia Therapeutics LimitedCompletedOvarian Neoplasms | Fallopian Tube Neoplasms | Peritoneal NeoplasmsUnited States, Australia
-
Tyra Biosciences, IncRecruitingSolid Tumor | Intrahepatic Cholangiocarcinoma | Metastatic Cholangiocarcinoma | Locally Advanced CholangiocarcinomaUnited States
-
AstraZenecaCompletedAsthma (Part 1) | COPD (Part 2)United Kingdom
-
Trevena Inc.TerminatedMigrainesUnited Kingdom
-
1ST Biotherapeutics, Inc.Merck Sharp & Dohme LLCRecruitingAdvanced Solid TumorUnited States
-
Harry T Whelan, MDCompletedNeurofibromatosesUnited States