BMX-001 + Paclitaxel in Adult Patients With Advanced, Recurrent, Metastatic Ovarian or Endometrial Cancer

NCT06620029 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BMX-GyCa-001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This research project addresses the urgent need for novel therapeutic strategies to overcome chemotherapy resistance and mitigate chemotherapy-induced peripheral neuropathy (CIPN) in patients with recurrent ovarian and endometrial cancers, which are among the most lethal gynecologic malignancies worldwide. The study focuses on BMX-001, a redox-active manganese metalloporphyrin compound that uniquely combines the ability to enhance anti-tumor efficacy and protect normal tissues from the toxic effects of chemotherapy, specifically paclitaxel (PTX). PTX, despite being a cornerstone of treatment, is associated with significant dose-limiting neurotoxicity, which severely impacts patients quality of life and limits the use of subsequent therapies. BMX-001 has demonstrated potential in preclinical models to not only augment the anti-tumor effects of PTX but also reduce PTX-induced neuropathy. The research will be conducted through a single-site, Phase 1/2 clinical trial led by the Duke Cancer Institute. The trial aims to determine the recommended Phase 2 dose of BMX-001 when combined with weekly PTX and to evaluate the clinical activity of this combination therapy. Specifically, the trial will assess the safety, tolerability, and potential to double the dose of BMX-001, which is hypothesized to further enhance the efficacy of PTX without increasing toxicity. The study\'s specific aims include establishing the recommended dose for expansion, assessing objective response rates (ORR), and quantifying the reduction in PTX-induced neurotoxicity using validated questionnaires and monofilament testing. The project also incorporates the analysis of circulating tumor DNA (ctDNA) as a biomarker for treatment response, adding a layer of precision to the evaluation of the therapy response impact on tumor burden. The outcomes of this research have the potential to significantly improve treatment protocols for patients with chemo-resistant gynecologic cancers by offering a therapy that enhances tumor control while protecting against debilitating side effects. Successful completion of this trial will lay the groundwork for larger, definitive trials and may extend the benefits of BMX-001 to other solid tumors, ultimately contributing to better survival outcomes and quality of life for a broader patient population.

Conditions

Ovarian Neoplasms; Endometrial Cancer, Endometrial Neoplasm

Keywords

BMX-001 plus Paclitaxel

Outcome Measures

Primary Outcomes (1)

• To determine the Recommended Phase 2 Dose of BMX-001 in combination with paclitaxel in a safety cohort of patients. This would be carried forward as the dose to be used in the expanded cohort portion of the trial.

  The metric used to characterize the primary outcome measure is the determination of the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of BMX-001 when administered in combination with paclitaxel. This will be based on the incidence of Dose- Limiting Toxicities (DLTs) observed in a safety cohort (dose escalation design) of patients over an 8-week period. The RP2D will be identified as the highest dose level at which a predefined acceptable DLT rate is observed, and this dose will be carried forward for use in the expanded cohort portion of the trial. We seek to determine if the current dose used in previous clinical trials dose can be safely doubled by giving two 28 mg doses s.c. that are 4-6 hours apart given on the first day of each week to optimize the opportunity for achieving efficacy.

  8 weeks

Secondary Outcomes (3)

• To evaluate preliminary efficacy based on objective response rate (ORR) using RECIST v 1.1 per investigator assessment on all evaluable subjects enrolled

  1 year

• To evaluate preliminary efficacy based on progression free survival (PFS) using RECIST v 1.1 per investigator assessment on all evaluable subjects enrolled

  1 year

• To describe patient-reported outcomes of health related quality of life (HRQoL) using Functional Assessment of Cancer Therapy/Gynecologic Oncology - Neurotoxicity (FACT/GOG-NTX) Questionnaire and monofilament testing

  1 year

Other Outcomes (4)

• To characterize the Cmax of BMX-001 when delivered in combination with PTX in recurrent ovarian or endometrial cancer in all evaluable subjects enrolled.

  2 weeks

• To characterize the Tmax and half life of BMX-001 when delivered in combination with PTX in recurrent ovarian or endometrial cancer in all evaluable subjects enrolled.

  2 weeks

• To characterize the area under the plasma concentration versus time curve of BMX-001 when delivered in combination with PTX in recurrent ovarian or endometrial cancer in all evaluable subjects enrolled.

  2 weeks

Study Arms (1)

BMX-001 + PTX

EXPERIMENTAL

All patients will be administered BMX-001 + PTX weekly on Days 1, 8, 15, and 22 of each 28 day cycle. BMX-001 is a SC injection while PTX is IV.

Drug: BMX-001; Drug: Paclitaxel (Taxol)

Interventions

BMX-001 DRUG

BMX-001 consists of a porphyrin ring with pyridyl groups attached at each of the four methane bridge carbons. The nitrogen in the pyridyl ring is at the 2 position and has a side chain consisting of six carbons with an ether linkage. A manganese atom is chelated into the porphyrin ring and is the active center of the molecule. This molecule is an enzymatic scavenger of free radical species operating at close to diffusion-limited rates. BMX-001 (7-28 mg) will be given by subcutaneous (s.c.) injection starting on Day 1, Day 8, Day 15, and Day 22 of each 28-day PTX treatment cycle.

BMX-001 + PTX

Paclitaxel (Taxol) DRUG

Paclitaxel will be given via IV infusion at a dose = 80 mg/m2 on Day 1, Day 8, Day 15, and Day 22 of each 28-day treatment cycle and will be sourced from standard commercial sources. Appropriate pretreatment prior to PTX will be given as per institutional standards. PTX management for any adverse event (AE) in any cycle, reasonably attributed to the chemotherapy agent that requires dose interruption should be managed per package insert, and/or institutional guidelines. Dose modification recommendations are provided in protocol to provide general consistency with dosing. Study Treatment dosing BMX-001 should continue even if the PTX is omitted. The subject may continue on PTX if the AE does not prohibit dosing per institutional practice. Grade 3 or higher infusion PTX reactions or recurrent infusion reactions may require permanent discontinuation of PTX. PTX may be continued in select patients using institutional desensitization protocol.

BMX-001 + PTX

Eligibility Criteria

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

You may qualify if:

• Recurrent advanced metastatic ovarian or endometrial cancer that progressed during or following prior SOC therapy
• Aged 18 years or older
• Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 1
• Ability to understand and willingness to give written informed consent
• Measurable disease according to RECIST v1.1 or assessable disease based on presence of malignancy pleural effusion or ascites, or disease that does not meet measurable criteria.
• Negative serum pregnancy test within 48 hours of dosing if indicated.
• Adequate bone marrow function
• Adequate hepatic function
• Adequate renal function as determined by calculated or measured creatinine clearance ≥30 mL/min (using Cockcroft- Gault equation) or serum creatinine \< 1.5 X institutional ULN
• Full recovery from all recent surgery on start date of treatment; at least 1 week must have elapsed from the time of a minor surgery (port placement at any time is acceptable); from the date of treatment at least 21 days must have elapsed from the time of a major surgery. Must have fully recovered from all surgery-related toxicities to Grade 1 or less
• At least 28 days between termination of prior anticancer or hormonal therapy and first administration of BMX-001

You may not qualify if:

• Residual Grade 2 peripheral neuropathy
• Untreated central nervous system (CNS) metastases (surgery and/or radiotherapy), Subjects requiring corticosteroid therapy for the management of CNS metastases may not be on \>10 mg/day prednisone or equivalent. Subjects that have demonstrated signs or symptoms of neurologic instability for 28 days or less prior to enrollment.
• Is being treated with concurrent anticancer therapy or other interventional treatments administered for their underlying cancer
• Subjects who have received prior therapy with weekly PTX in the recurrent setting.
• Clinically significant cardiac disease.
• History of or present CNS disease unrelated to cancer, unless adequately treated with standard medical therapy (eg, uncontrolled seizures)
• Nonhealing wound, ulcer, or bone fracture
• Serious active infection requiring IV antibiotics and/or hospitalization within 7 days of enrollment
• Known severe hypersensitivity to any of the study drugs or excipients, including history of allergic, anaphylactic, or other severe hypersensitivity reactions to fusion proteins, products containing Cremophor EL (eg, cyclosporin for injection concentrate and teniposide for injection concentrate)
• Require regular blood transfusions, platelet transfusions, or granulocyte colony stimulating factor.
• Refusal to use highly effective method of contraception or to practice true abstinence during treatment and for 6 months after the last dose of study drug
• Pregnant or breast feeding;
• Presence of any other condition that may increase the risk associated with enrollment on the study, interfere with data interpretation, or make the patient inappropriate for study enrollment in the opinion of the treating investigator
• Prior treatment with or participation in a study with BMX-001
• A history of additional risk factors for Torsades de Pointes (e.g., congestive heart failure, hypokalemia, known family history of Long QT Syndrome).

Sponsors & Collaborators

• BioMimetix JV, LLC: lead

Study Sites (1)

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• James Crapo, MD

  BioMimetix JV, LLC

  STUDY DIRECTOR

• Angeles Secord

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Penchev

CONTACT

610-308-6640; sara.penchev@bmxpharma.com

Study Design

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

Model Details: Dose finding stage followed by an expansion cohort.

Study Record Dates

• First Submitted: September 18, 2024
• First Posted: October 1, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: October 1, 2024

Record last verified: 2024-09

Locations

US (1)