BXQ-350 in Newly Diagnosed Metastatic Colorectal Carcinoma

NCT ID: NCT05322590

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

195 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-09

Study Completion Date

2029-04-30

Brief Summary

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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.

Detailed Description

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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).Due to the presumed mechanism of action of BXQ-350, Bexion anticipates that it may have an impact on ceramides, sphingosine-1-phosphate (S1P), and inflammatory cytokine levels. In addition, pre-clinical results demonstrated that BXQ-350 induced neurite generation and protection in vitro in the PC-12 and NS20Y cell lines and significantly decreased oxaliplatin-induced cold allodynia in a model of CIPN. Thus BXQ-350 may represent a new approach to deliver a neuropathy benefit.

The unique combination of BXQ-350 along with its proven safety profile, potential efficacy, and possible neuropathy benefit makes BXQ-350 a worthwhile candidate to use in combination with standard of care treatment for mCRC to not only enhance the standard treatment of mCRC, but also to evaluate its ability to alleviate side effects related to oxaliplatin-induced sensory neurotoxicity.

Conditions

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Metastatic Colorectal Carcinoma Neuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Stage 1 (open label)/Stage 2 (Randomized, Placebo controlled, Double Blind)

Study Groups

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BXQ-350

BXQ-350 will be administered by IV infusion

Group Type EXPERIMENTAL

BXQ-350

Intervention Type 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.

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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)

Interventions

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BXQ-350

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.

Intervention Type DRUG

Placebo

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)

Intervention Type OTHER

Other Intervention Names

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SapC-DOPS

Eligibility Criteria

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Inclusion Criteria

Participants who meet the following criteria will be considered eligible to participate in the clinical study:

1. Age ≥ 18 years of age at the time of signing the informed consent.
2. Participants have newly diagnosed Stage IV metastatic adenocarcinoma of the colon / rectum.
3. Have measurable disease at baseline based on RECIST 1.1 as determined by the local site Investigator / radiology assessment.
4. Have a life expectancy \> 3 months.
5. 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.
6. 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.
7. 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.
8. Have acceptable bone marrow function defined as:

* Absolute neutrophil count ≥ 1,500 cells / 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).
9. Have acceptable coagulation parameters (anti-coagulation allowed) defined as:

* International normalized ratio ≤ 2 x ULN unless on anticoagulation or prothrombin time within normal limits.
* Activated partial thromboplastin time within normal limits.
10. Have a negative serum pregnancy test result at screening (females of childbearing potential \[FCBP\] only). Not applicable to participants who are surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or who are post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
11. Contraceptive use by men and women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. FCBP whose partner(s) are non-sterilized males and non-sterilized male participants whose sexual partner(s) are FCBP must abstain from heterosexual activity or agree to use an acceptable method of contraception according to the following guidelines:

* The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the entire period of risk associated with study interventions and the preferred and usual lifestyle of the participant. Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods), the rhythm method, and withdrawal are not acceptable methods of contraception.
* Non-sterilized Male Participants:

* Must use an acceptable method of contraception such as male condom plus spermicide during the entire period of risk associated with study interventions which includes the total duration of the study and the drug washout period (6 months after the last dose of study intervention) and refrain from sperm donation or banking throughout this period.
* Vasectomized males are considered fertile and should still use a male condom plus spermicide as indicated above.
* Even if the female partner is pregnant, male participants should still use a condom plus spermicide, as indicated above..
* Female partners (of childbearing potential) of male participants must also use a highly effective method of contraception during the entire period of risk associated with study interventions as described above.
* FCBP

* Must use a highly effective method of contraception and avoid breastfeeding during the entire period of risk associated with study interventions which includes the total duration of the study and the drug washout period (9 months after the last dose of study intervention) and refrain from egg donation or banking throughout this period.
* Non-sterilized male partners must also use a male condom plus spermicide during the entire period of risk associated with study interventions as described above.
* A highly effective method of contraception is defined as one that results in a low failure rate (less than 1% per year) when used consistently and correctly. Note that some contraception methods are not considered highly effective. The participants chosen method(s) must be confirmed as highly effective prior to study entry.
12. Participant is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

Participants must not meet any of the following criteria:

1. Have locally confirmed DNA-mismatch repair deficient or microsatellite instability (MSI) status - high Stage IV colorectal cancer.
2. 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.
3. 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.
4. Have Type 1 or 2 diabetes mellitus.
5. Have Reversible Posterior Leukoencephalopathy.
6. Have a history of or evidence of active gastrointestinal perforation or gastrointestinal fistula.
7. Have a family history of a genetic / familial neuropathy.
8. Have pre-existing clinical neuropathy ≥ Grade 2 per CTCAE v5.0 from any cause.
9. 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.
10. 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.
11. 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 with QTc \> 470 milliseconds at screening.
12. Have uncontrolled severe infections (acute or chronic) including HIV, Hepatitis B or C
13. Have active poor wound healing (delayed healing, wound infection or fistula).
14. Have evidence of active, clinically significant bleeding (e.g., gastrointestinal bleeding, hemoptysis, or gross hematuria) at screening. No bleeding diathesis, hemorrhage, or arterial/ venous thrombotic events within 6 months prior to initiation of screening, including transient ischemic attack, cerebrovascular accident, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction. Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) or any other arterial thrombotic event are also ineligible.
15. Are breast feeding or pregnant, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test.
16. Have other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment contraindicate the participant's participation in the clinical study or obscure proper assessment of safety and toxicity of the prescribed regimen.
17. Have received prior treatment with any investigational drug within 4 weeks (28 days) prior to randomization.
18. Have received prior treatment with neurotoxic chemotherapy including but not limited to oxaliplatin, cisplatin, a taxane, or a vinca alkaloid.
19. Have received prior treatment with any anti-VEGF agent.
20. Are receiving any agent for the treatment, prevention, or with known/hypothesized efficacy for peripheral neuropathy; including but not limited to gabapentin, pregabalin, venlafaxine, duloxetine, amitriptyline, nortriptyline, or anti-neuropathic pain topical cream.
21. Have a known sensitivity to the components of BXQ-350 (SapC and DOPS).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ICON plc

INDUSTRY

Sponsor Role collaborator

CTI Clinical Trial and Consulting Services

OTHER

Sponsor Role collaborator

Bexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chief Scientific Officer

Role: STUDY_DIRECTOR

Bexion Pharmaceuticals, Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

UC Irvine Health

Orange, California, United States

Site Status

Pacific Hematology Oncology Associates

San Francisco, California, United States

Site Status

Sylvester Comprehensive Cancer Center, University of Miami Hospitals and Clinics

Miami, Florida, United States

Site Status

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

St. Elizabeth Healthcare

Edgewood, Kentucky, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

University of Louisville, James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

University Medical Center New Orleans

New Orleans, Louisiana, United States

Site Status

Stony Brook Cancer Center

Stony Brook, New York, United States

Site Status

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Countries

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United States

Other Identifiers

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BXQ-350.AG

Identifier Type: -

Identifier Source: org_study_id