A Study of BXQ-350 in Children and Young Adults With Relapsed Solid Tumors

NCT03967093 | Terminated Phase 1 FDA Drug

• 1 other identifier: BXQ-350.AB
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate the safety of BXQ-350 and determine the maximum tolerated dose (MTD) in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors. All patients will receive BXQ-350 by intravenous (IV) infusion. 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 use the MTD to further assess the safety of BXQ-350 as well as preliminary anti-tumor activity.

Conditions

Neoplasms

Keywords

solid tumor; brain tumor; DIPG; ependymoma

Outcome Measures

Primary Outcomes (5)

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

  To determine the safety of BXQ-350 in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors, 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.

  6 months

• Part 1 - Maximum Tolerated Dose

  To determine the maximum tolerated dose (MTD) of BXQ-350, when given as a single agent at escalating doses, according to the investigational product (IP) related dose limiting toxicities (DLTs) in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors

  6 months

• Part 2 - RECIST

  To assess the preliminary antitumor activity of BXQ-350, given as a single agent at the MTD, or highest planned dose level (DL), 3.2 mg/kg, in the absence of a Maximum Administered Dose (MAD). Antitumor activity is defined as maximal radiological response during treatment using: • Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria for relapsed solid tumors

  6 months

• Part 2 - RANO

  To assess the preliminary antitumor activity of BXQ-350, given as a single agent at the MTD, or highest planned dose level (DL), 3.2 mg/kg, in the absence of a Maximum Administered Dose (MAD). Antitumor activity is defined as maximal radiological response during treatment using: • Radiographic Response Criteria (RRC) for recurrent malignant brain tumors

  6 months

• Part 2 - INRC

  To assess the preliminary antitumor activity of BXQ-350, given as a single agent at the MTD, or highest planned dose level (DL), 3.2 mg/kg, in the absence of a Maximum Administered Dose (MAD). Antitumor activity is defined as maximal radiological response during treatment using: • International Neuroblastoma Response Criteria (INRC) for recurrent neuroblastomas

  6 months

Secondary Outcomes (3)

• Progression-Free Survival (PFS-6)

  6 months

• Time to Response

  6 months

• Duration of Response

  6 months

Study Arms (5)

Part 1 Dose Escalation: Safety and Tolerance

EXPERIMENTAL

Sequential cohorts of patients with relapsed solid tumors, including malignant brain tumors, 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 (3.2 mg/kg) is reached.

Drug: BXQ-350

Part 2: Ependymoma Patients

EXPERIMENTAL

Cohort of patients with recurrent ependymoma will be enrolled and administered BXQ-350 at the MTD determined in Part 1 or at 3.2 mg/kg if the MAD is not reached.

Drug: BXQ-350

Part 2: Brain Tumor Patients

EXPERIMENTAL

Cohort of patients with recurrent malignant brain tumors will be enrolled and administered BXQ-350 at the MTD determined in Part 1 or at 3.2 mg/kg if the MAD is not reached.

Drug: BXQ-350

Part 2: DIPG Patients

EXPERIMENTAL

Cohort of patients with recurrent diffuse intrinsic pontine glioma (DIPG) will be enrolled and administered BXQ-350 at the MTD determined in Part 1 or at 3.2 mg/kg if the MAD is not reached.

Drug: BXQ-350

Part 2: Other Solid Tumor Patients

EXPERIMENTAL

Cohort of patients with relapsed non-central nervous system (CNS) solid tumors will be enrolled and administered BXQ-350 at the MTD determined in Part 1 or at 3.2 mg/kg if the MAD is not reached.

Drug: BXQ-350

Interventions

BXQ-350 DRUG

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). BXQ-350 is administered by intravenous (IV) infusion over a minimum of six 28-day cycles.

Also known as: SapC-DOPS

Part 1 Dose Escalation: Safety and Tolerance; Part 2: Brain Tumor Patients; Part 2: DIPG Patients; Part 2: Ependymoma Patients; Part 2: Other Solid Tumor Patients

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• Are male or female aged ≥ 1 to 30 years
• Have histologically or cytologically confirmed relapsed solid tumor cancer, including recurrent malignant brain tumors, for which there is no further standard therapy or when standard therapy is contraindicated • Recurrent malignant brain tumors: must have shown unequivocal evidence for recurrence or progression by MRI scan or must have histologically proven tumor recurrence • Recurrent malignant brain tumors: must have previously received standard of care treatment at initial diagnosis (radiation and/or chemotherapy)
• Recurrent malignant brain tumors receiving glucocorticoid therapy: must be on stable or decreasing equivalent daily dose of glucocorticoids for 2 weeks (14 days) prior to dose assignment
• Recurrent embryonal tumors or atypical teratoid rhabdoid tumors (AT/RT): must have previously received standard of care therapy including either chemotherapy and radiation therapy or high dose chemotherapy with autologous hematopoietic stem cell support
• Grade II or III recurrent ependymoma, including RELA fusion-positive ependymoma: must have previously received radiation therapy
• Have measurable or non-measurable disease per RECIST v1.1 for relapsed solid tumors, RRC for recurrent malignant brain tumors, and INRC for recurrent neuroblastomas
• Have Lansky (age 1 - 15) / Karnofsky (age ≥ 16) Performance Score of \>50 or Eastern Cooperative Oncology Group Performance Status (ECOG PS) (age ≥ 18) of 0 - 2
• Have acceptable liver function defined as:
• Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN) for the study site (in subjects with known Gilbert Syndrome, total bilirubin ≤ 3 × ULN, with direct bilirubin ≤ 1.5 × ULN)
• Aspartate Transaminase (AST), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alanine Transaminase (ALT), Serum Glutamic-Pyruvic Transamine (SGPT) ≤ 3 × ULN (if liver metastases are present, then ≤ 5 × ULN is allowed)
• Serum albumin ≥ 3 g/dL
• Have acceptable renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70 mL/min/1.73m² or a maximum serum creatinine (mg/dL)\* based on age/gender as follows:

You may not qualify if:

• \- Subjects must not meet any of the following criteria:
• Have a concurrent or second malignancy
• Have lymphoma
• Have Grade I ependymoma
• Relapsed solid tumors: have symptomatic brain metastases or leptomeningeal disease
• Relapsed solid tumors: have received
• anticancer therapies within 2 weeks prior to dose assignment (including radiation therapy, cytotoxic agents, targeted agents or endocrine therapy)
• myelosuppressive agents within 3 weeks prior to dose assignment
• monoclonal antibodies within 4 weeks prior to dose assignment
• growth factors within 2 weeks of dose assignment
• other immunotherapy (tumor vaccine, cytokines) within 4 weeks of dose assignment
• Recurrent malignant brain tumors: have received
• anticancer therapies including: radiation therapy to current site of disease within 3 weeks dose assignment; targeted agent therapy within 2 weeks of dose assignment; nitrosoureas within 6 weeks of dose assignment; procarbazine within 3 weeks of dose assignment; other cytotoxic agents withing 4 weeks of dose assignment
• myelosuppressive agents within 4 weeks prior to dose assignment
• monoclonal antibodies within 4 weeks prior to dose assignment

Sponsors & Collaborators

• Bexion Pharmaceuticals, Inc.: lead
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (2)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45226, United States

Location

Nationwide Children's

Columbus, Ohio, 43205, United States

Location

MeSH Terms

Conditions

Neoplasms; Brain Neoplasms; Ependymoma

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 dose escalation - sequential cohorts of patients 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, the highest planned dose level. Part 2 - patients will be enrolled and administered BXQ-350 at the Part 1 MTD or at the highest planned dose level

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 30, 2019
• Study Start: April 15, 2019
• Primary Completion: January 3, 2020
• Study Completion: January 17, 2020
• Last Updated: July 22, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)