BXQ-350 in Newly Diagnosed Metastatic Colorectal Carcinoma

NCT05322590 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BXQ-350.AG
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 12

Brief Summary

The study will assess the safety and efficacy of BXQ-350 plus modified FOLFOX7 (mFOLFOX7) and bevacizumab in participants who have newly diagnosed metastatic adenocarcinoma of the colon/rectum. The study will also evaluate if the administration of BXQ-350 with mFOLFOX7 and bevacizumab may diminish oxaliplatin induced sensory neurotoxicity, enabling participants to receive the total and planned doses of mFOLFOX7. All participants will receive BXQ-350 by intravenous (IV) infusion along with standard of care doses of mFOLFOX and bevacizumab. The study is divided into two stages: Stage 1 will be open label and will enroll participants at increasing dose levels of BXQ-350 in order to determine the Stage 2 dose. Stage 2 will be blinded; participants will receive BXQ-350 at the established Stage 1 dose or placebo.

Conditions

Metastatic Colorectal Carcinoma; Neuropathy

Outcome Measures

Primary Outcomes (3)

• Recommended Phase 2 Dose

  To determine the recommended phase 2 dose of BXQ-350, when given with mFOLFOX7 and bevacizumab, according to the investigational product (IP) related dose limiting toxicities (DLTs).

  6 months

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

  To determine the safety of BXQ-350 when given with mFOLFOX7 and bevacizumab, 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

• Objective Response Rate (ORR)

  To determine the ORR of BXQ-350 when given with mFOLFOX7 and bevacizumab. ORR is defined as the percentage of participants with evidence of a complete or partial response as per the Response Evaluation Criteria in Solid Tumors (RECIST).

  6 months

Secondary Outcomes (8)

• Peak Plasma Concentration (Cmax)

  6 months

• Overall Survival (OS)

  6 months

• Progression Free Survival (PFS)

  6 months

• Duration of Response (DoR)

  6 months

• Disease Control Rate (DCR)

  6 months

Study Arms (2)

BXQ-350

EXPERIMENTAL

BXQ-350 will be administered by IV infusion

Drug: BXQ-350

Placebo

PLACEBO COMPARATOR

Placebo (0.9% normal saline) will be administered by IV infusion (Stage 2 only)

Other: Placebo

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 will be administered by intravenous (IV) infusion over six months and continued for an additional 20 months for participants who remain eligible.

Also known as: SapC-DOPS

BXQ-350

Placebo OTHER

Placebo will be 0.9% normal saline of matching volume to BXQ-350 administered by intravenous (IV) infusion over six months and continued for an additional 20 months for participants who remain eligible (Stage 2 only)

Placebo

Eligibility Criteria

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

You may qualify if:

• Participants who meet the following criteria will be considered eligible to participate in the clinical study:
• Age ≥ 18 years of age at the time of signing the informed consent.
• Participants have newly diagnosed Stage IV metastatic adenocarcinoma of the colon / rectum.
• Have measurable disease at baseline based on RECIST 1.1 as determined by the local site Investigator / radiology assessment.
• Have a life expectancy \> 3 months.
• Have ECOG Performance Status of 0 or 1.
• Participants 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 (ULN) for the study site; in participants 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 transaminase (SGPT) ≤ 3 x ULN (if liver metastases are present, then ≤ 5 x ULN is allowed).
• Serum albumin ≥ 3 g/ dL.
• Have acceptable renal function defined as:
• Creatinine clearance ≥ 50 mL/minute calculated using the Cockcroft-Gault formula (Cockcroft 1976): CCr = {((140 - age) x weight kg) / (72 x SCr)} x 0.85 (if female).
• Urine dipstick protein \< 1 + (30 - 70 mg/dL), urine protein/creatinine ratio of \< 1, OR 24 hour urine protein \< 1g/24 hours.
• Have acceptable bone marrow function defined as:

You may not qualify if:

• Participants must not meet any of the following criteria:
• Have locally confirmed DNA-mismatch repair deficient or microsatellite instability (MSI) status - high Stage IV colorectal cancer.
• Participants with brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases and are off steroids for at least 7 days.
• Have a concurrent malignancy or have had another malignancy within the past 5 years prior to screening that is expected to alter life expectancy or may interfere with disease assessment.
• Have Type 1 or 2 diabetes mellitus.
• Have Reversible Posterior Leukoencephalopathy.
• Have a history of or evidence of active gastrointestinal perforation or gastrointestinal fistula.
• Have a family history of a genetic / familial neuropathy.
• Have pre-existing clinical neuropathy ≥ Grade 2 per CTCAE v5.0 from any cause.
• Have had major surgery other than a minor outpatient procedure within 28 days prior to randomization 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 \> 150/90 mmHg on at least 2 repeated determinations on separate days during screening period.
• 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.

Sponsors & Collaborators

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

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

UC Irvine Health

Orange, California, 92868, United States

Location

Pacific Hematology Oncology Associates

San Francisco, California, 94115, United States

Location

Sylvester Comprehensive Cancer Center, University of Miami Hospitals and Clinics

Miami, Florida, 33136, United States

Location

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

St. Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

University of Louisville, James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Chief Scientific Officer

  Bexion Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Stage 1 (open label)/Stage 2 (Randomized, Placebo controlled, Double Blind)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Enrollment will proceed in 2 stages. In the Stage 1 (open label) safety run-in phase, participants are enrolled and treated in cohorts of 3 in order to reach a maximum tolerated dose (MTD) or recommended Phase 2 Dose (RP2D). After the MTD/RP2D is established, a cohort expansion of up to 30 participants will be conducted at the RP2D. Stage 1 enrollment was completed in November 2024. In Stage 2, eligible participants will be randomized in a 1:1 ratio to receive either BXQ-350 at the RP2D or placebo (0.9% normal saline) intravenously (IV) administered in combination with mFOLFOX7 and bevacizumab.

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: April 12, 2022
• Study Start: January 9, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2029
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

US (12)