Phase 1 Study of BXQ-350 in Adult Patients With Advanced Solid Tumors

NCT02859857 | Completed Phase 1 DMC

• 1 other identifier: BXQ-350.AA
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 4

Brief Summary

The objective of this study is to characterize the safety profile and determine the maximum tolerate 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 patients with advanced solid tumors. Secondarily to assess the preliminary antitumor activity of BXQ-350 in solid tumors and recurrent high grade gliomas.

Conditions

Neoplasms

Keywords

Glioblastoma Multiforme; Solid Tumors; Ependymoma

Outcome Measures

Primary Outcomes (4)

• Part 1-MTD

  · To determine the maximum tolerate 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 patients with advanced solid tumors

  12 months

• Part 2-RECIST

  ·To assess preliminary antitumor activity, defined as maximal radiological response during treatment using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v1.1) criteria for solid tumors.

  12 months

• Part 2-RANO

  To assess preliminary antitumor activity, defined as maximal radiological response during treatment Revised Assessment in Neuro-Oncology (RANO) criteria for recurrent high grade glioma (HGG), of BXQ-350 given as a single agent at the MTD, or highest planned dose level (DL), in the absence of a Maximum Administered Dose (MAD).

  12 months

• Part 3 - RECIST

  To assess preliminary antitumor activity, defined as maximal radiological response during treatment using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v1.1) criteria for solid tumors

  12 months

Secondary Outcomes (7)

• Part 2- Area under Curve (AUC)

  12 months

• Part 2-Cmax

  12 months

• Part 2-half life

  12 months

• Part 2-CL

  12 months

• Part 2-Progression-free survival (PFS-6)

  12 months

Study Arms (6)

Rising dose; safety and tolerance

EXPERIMENTAL

Sequential cohorts of patients with advanced solid tumors and recurrent high-grade gliomas will be be treated with escalating doses of BXQ-350 until the MTD is established, or in the absence of a MAD, the highest planned DL is reached.

Drug: BXQ-350

Solid tumor patients

EXPERIMENTAL

Cohort of patients with advanced solid tumors administered BXQ-350 at the MTD determined in Part 1 or at the highest planned DL if the MAD is not reached.

Drug: BXQ-350

Glioblastoma Multiforme patients

EXPERIMENTAL

Cohort of patients with recurrent high-grade gliomas administered BXQ-350 at the MTD determined in Part 1 or at the highest planned DL if the MAD is not reached.

Drug: BXQ-350

Gastrointestinal tumor patients

EXPERIMENTAL

Cohort of patients with Gastrointestinal tumors as defined in the protocol and administered BXQ-350 at the 2.4 mg/kg dose level.

Drug: BXQ-350

Ependymoma tumor patients

EXPERIMENTAL

Cohort of patients with ependymoma administered BXQ-350 at the 2.4 mg/kg dose level.

Drug: BXQ-350

Solid tumor patients other than HGG

EXPERIMENTAL

Cohort of patients with advanced solid tumors other than HGG administered BXQ-350 at the 2.4 mg/kg dose level.

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. When both the components are assembled together stable SapC-DOPS nanovesicles are formed(clinical formulation BXQ-350).

Also known as: SapC-DOPS

Ependymoma tumor patients; Gastrointestinal tumor patients; Glioblastoma Multiforme patients; Rising dose; safety and tolerance; Solid tumor patients; Solid tumor patients other than HGG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each patient must meet the following criteria:
• Provide signed, written informed consent prior to the initiation of any study-specific procedures
• Have histologically or cytologically confirmed diagnosis of advanced solid tumor cancer (excluding lymphomas) for which there is no further standard therapy or when standard therapy is contraindicated. Patients with HGG must have shown unequivocal evidence for recurrence or progression by MRI scan or must have histologically proven tumor recurrence.
• Patients with HGG: Have previously received radiotherapy and temozolomide
• For patients with HGG and receiving glucocorticoid therapy, must be on stable or decreasing equivalent daily dose of glucocorticoids for 2 weeks (14 days) prior to dose assignment
• Have measurable or non-measurable disease per RECIST 1.1 criteria for solid tumors and RANO criteria for HGG
• Are males or females aged ≥ 18 years
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 - 2
• Have acceptable liver function defined as:
• Total serum bilirubin ≤ 1.5 × upper limit of normal for the study site (ULN) (in patients 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:
• Serum creatinine ≤ 1.5 × ULN, OR calculated creatinine clearance ≥ 45 mL/min for patients with creatinine levels above 1.5 mg/dL
• Have acceptable bone marrow function defined as:

You may not qualify if:

• Patients must not meet any of the following criteria:
• Have a concurrent malignancy or have had another malignancy within 1 year prior to initiation of screening (with the exception of adequately treated basal or squamous cell carcinoma, melanoma in situ, early-stage prostate cancer (T1a-cN0M0), ductal carcinoma in situ of the breast or cervical carcinoma in situ)
• Patients with solid tumors: Have received anticancer therapies, including radiation therapy, cytotoxic agents, targeted agents or endocrine therapy within 2 weeks prior to dose assignment
• Patients with HGG: Have received anticancer therapies including: radiation therapy to current site of disease within 12 weeks of 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, or other cytotoxic agents within 4 weeks of dose assignment
• Have not recovered from toxicity of prior therapy defined as a return to \< grade 1 at the time of dose assignment, graded according to CTCAE v4.03 (excluding alopecia, neuropathy, and lymphopenia)
• Have received prior treatment with any investigational drug within 4 weeks prior to dose assignment
• Have had major surgery other than a minor outpatient procedure within 4 weeks 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 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
• ECG with correctd QT interval (QTc) \>450 msec in males or \>470 msec in females at screening
• Have a known history of HIV seropositivity
• Are pregnant or nursing (lactating), 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 symptomatic brain metastases or leptomeningeal disease

Sponsors & Collaborators

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

Study Sites (4)

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

University of Cincinnati Barrett Center

Cincinnati, Ohio, 45219, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Neoplasms; Glioblastoma; Ependymoma

Condition Hierarchy (Ancestors)

Astrocytoma; 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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2016
• First Posted: August 9, 2016
• Study Start: September 1, 2016
• Primary Completion: June 17, 2019
• Study Completion: June 15, 2020
• Last Updated: July 22, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)