A Phase 1/2, Open-label Clinical Trial to Evaluate Safety and Efficacy of Combination Paclitaxel and BMX-001, in Adult Patients With Advanced, Recurrent, Metastatic Ovarian or Endometrial Cancer

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.

Description

Eligibility

Age range

18+ years

Sex

Female

Healthy volunteers

No

Interventions

• Drug
  BMX-001

  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.

• Drug
  Paclitaxel (Taxol)

  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.

Location