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Diffuse Intrinsic Pontine GliomaPhase 1KONQUERNCT04771897

A Study of BXQ-350 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) or Diffuse Midline Glioma (DMG)

A Phase 1 study testing BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance and BXQ-350 - Part 2 BXQ-350 Tumor and Plasma Concentrations in people with Diffuse Intrinsic Pontine Glioma and Diffuse Midline Glioma, H3 K27M-Mutant, run by Bexion Pharmaceuticals, Inc. at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will evaluate the safety of BXQ-350 and determine the maximum tolerated dose (MTD) in children with newly diagnosed DIPG or DMG. All patients will receive BXQ-350 by intravenous (IV) infusion and radiation therapy. Read more about this study

Who is it for?
Ages 1 year to 30 years
What is being tested?
BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance and BXQ-350 - Part 2 BXQ-350 Tumor and Plasma Concentrations
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesUnited States
Study dates
24 May 2021to 4 Oct 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 30Show fewer
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45226

  • Nationwide Children's

    Columbus, Ohio, 43205

Other trials in United States

About this study

Official title: 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)

This study will evaluate the safety of BXQ-350 and determine the maximum tolerated dose (MTD) in children with newly diagnosed DIPG or DMG. All patients will receive BXQ-350 by intravenous (IV) infusion and radiation therapy. The study is divided into two parts: Part 1 will enroll patients at increasing dose levels of BXQ-350 in order to determine the MTD. Part 2 will enroll patients requiring a biopsy in order to assess BXQ-350 concentrations in the biopsied tumor.

Read the 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.)

Being tested
BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance, BXQ-350 - Part 2 BXQ-350 Tumor and Plasma Concentrations
Keywords
DIPG, DMG, brain tumor, glioma
Medical subject headings
Diffuse Intrinsic Pontine Glioma, Brain Neoplasms, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BXQ-350 - Part 1 Dose Escalation: Safety and ToleranceDrug

    Also called SapC-DOPS

    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.

  • BXQ-350 - Part 2 BXQ-350 Tumor and Plasma ConcentrationsDrug

    Also called SapC-DOPS

    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.

Study groups in NCT04771897
Study groupRoleWhat they receive
Part 1 Dose Escalation: Safety and ToleranceExperimentalSequential 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.
Receives: Drug: BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance
Part 2 BXQ-350 Tumor and Plasma ConcentrationsExperimentalNewly 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.
Receives: Drug: BXQ-350 - Part 2 BXQ-350 Tumor and Plasma Concentrations

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0

    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.

    Measured: 12 months

  2. Part 1 - Maximum Tolerated Dose

    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.

    Measured: 12 months

  3. Part 2 - BXQ-350 Concentration in Tumor Samples

    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).

    Measured: 12 months

  4. Part 2 - BXQ-350 Concentration in Plasma Samples

    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).

    Measured: 12 months

Secondary outcomes (8)

  1. Objective Response Rate (ORR)

    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.

    Measured: 12 months

  2. Overall Survival (OS)

    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.

    Measured: 12 months

  3. Quality of Life (QoL)

    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.

    Measured: 12 months

  4. Concentration of drug at steady state (Css)

    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).

    Measured: 12 months

  5. Exposure to BXQ-350 - area under the curve (AUC)

    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).

    Measured: 12 months

  6. Exposure to BXQ-350 - clearance (CL)

    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).

    Measured: 12 months

  7. Exposure to BXQ-350 - volume of distribution (Vd)

    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).

    Measured: 12 months

  8. Exposure to BXQ-350 - half-life (t½)

    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).

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2021
  2. Study start24 May 2021
  3. Primary completion4 Oct 2024
  4. Study completion4 Oct 2024

Why it stopped: Bexion Pharmaceuticals has decided to close the BXQ-350.AD study to enrollment prior to the anticipated enrollment goal. Justification for this decision is due to slow enrollment and the competitive landscape of the indication.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04771897
Sponsor's protocol ID
BXQ-350.AD
Acronym
KONQUER
Status last verified
Dec 2024
First submitted
17 Feb 2021
Last updated
20 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance and BXQ-350 - Part 2 BXQ-350 Tumor and Plasma Concentrations in people with Diffuse Intrinsic Pontine Glioma and Diffuse Midline Glioma, H3 K27M-Mutant, run by Bexion Pharmaceuticals, Inc. at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Bexion Pharmaceuticals has decided to close the BXQ-350.AD study to enrollment prior to the anticipated enrollment goal. Justification for this decision is due to slow enrollment and the competitive landscape of the indication.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0 (time frame: 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04771897.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.

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