BMX-001 + Paclitaxel in Adult Patients With Advanced, Recurrent, Metastatic Ovarian or Endometrial Cancer
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorBioMimetix JV, LLC
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
BMX-001
DrugBMX-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.
Paclitaxel (Taxol)
DrugPaclitaxel 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.
Treatment groups
27 Participants
are divided into 1 treatment groupGroup A: BMX-001 + PTXExperimental treatment 2 interventions
Trial outcomes
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.
Time frame
8 weeksSecondary outcomes
1
To evaluate preliminary efficacy based on objective response rate (ORR) using RECIST v 1.1 per investigator assessment on all evaluable subjects enrolled
The metric used to characterize the secondary outcome measure is the Objective Response Rate (ORR), which will be assessed using RECIST v1.1 criteria. This will be measured as the proportion of evaluable subjects who achieve a complete or partial response to the treatment as determined by the investigator. Evaluations will be conducted at baseline, post-treatment at every 8- week interval during the first 48 weeks following treatment initiation (Cycle 1, Day 1), and every 12 weeks thereafter until disease progression or study termination.
Time frame
1 year2
To evaluate preliminary efficacy based on progression free survival (PFS) using RECIST v 1.1 per investigator assessment on all evaluable subjects enrolled
The metric used to characterize the secondary outcome measure is the Progression Free Survival (PFS) which will be assessed using RECIST v1.1 criteria. This will be measured as the proportion of evaluable subjects who achieve a complete or partial response to the treatment as determined by the investigator. Evaluations will be conducted at baseline, post-treatment at every 8- week interval during the first 48 weeks following treatment initiation (Cycle 1, Day 1), and every 12 weeks thereafter until disease progression or study termination.
Time frame
1 year3
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
The metric used to characterize this secondary outcome measure is patient-reported outcomes (PRO) related to health-related quality of life (HRQoL) and overall quality of life (QoL). These outcomes will be assessed using the FACT/GOGNTX Questionnaire and monofilament testing. Measurements will be taken at baseline and then every 28 days until disease progression. The assessments will provide insights into the impact of the treatment on patients\' physical, emotional, and functional well-being, as well as the extent of peripheral neuropathy experienced during the study.
Time frame
1 yearOther outcomes
1
To characterize the Cmax of BMX-001 when delivered in combination with PTX in recurrent ovarian or endometrial cancer in all evaluable subjects enrolled.
The metric used to characterize this outcome measure is Cmax of BMX-001 when administered in combination with paclitaxel (PTX) in patients with recurrent ovarian or endometrial cancer. Pharmcaokinetic samples will be collected on Day 1 and Day 8 at pre-dose, and at 30 minutes, 1 hour, and 2 hours postdose. For Dose Levels 2 and 3 (with two doses of BMX-001 per day), samples will be collected on Day 1 and Day 8 at pre-dose, 30 minutes, 1 hour, and 4-6 hours post-dose, and then at 30 minutes and 1 hour post-second dose.
Time frame
2 weeks2
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.
The metric used to characterize this outcome measure is Tmax and half-life of BMX-001 when administered in combination with paclitaxel (PTX) in patients with recurrent ovarian or endometrial cancer. Pharmacokinetic samples will be collected on Day 1 and Day 8 at pre-dose, and at 30 minutes, 1 hour, and 2 hours postdose. For Dose Levels 2 and 3 (with two doses of BMX-001 per day), samples will be collected on Day 1 and Day 8 at pre-dose, 30 minutes, 1 hour, and 4-6 hours post-dose, and then at 30 minutes and 1 hour post-second dose.
Time frame
2 weeks3
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.
The metric used to characterize this outcome measure is the area under the plasma concentration versus time curve (AUC) of BMX-001 when administered in combination with paclitaxel (PTX) in patients with recurrent ovarian or endometrial cancer. Pharmacokinetics samples will be collected on Day 1 and Day 8 at pre-dose, and at 30 minutes, 1 hour, and 2 hours postdose. For Dose Levels 2 and 3 (with two doses of BMX-001 per day), samples will be collected on Day 1 and Day 8 at pre-dose, 30 minutes, 1 hour, and 4-6 hours post-dose, and then at 30 minutes and 1 hour post-second dose.
Time frame
2 weeks4
To assess correlations between B cell lymphoma/ leukemia 2 (BCL2), Nrf2, TNF- # and NFkB RNA and protein expression and activation, ctDNA, and clinical endpoints (response and progressionfree survival) in all evaluable subjects enrolled
The metric used to characterize this outcome measure is the correlation between molecular biomarkers and clinical outcomes. Specifically, the study will assess the expression and activation levels of B cell lymphoma/leukemia 2 (BCL2), Nrf2, TNF-alpha, and NFkB RNA and proteins, as well as circulating tumor DNA (ctDNA). These molecular data will be correlated with clinical endpoints, including response to treatment (ORR) and progression-free survival (PFS). Samples will be collected at baseline and post-treatment to evaluate these associations in all evaluable subjects. This analysis aims to identify potential biomarkers that could predict treatment efficacy and disease progression.
Time frame
1 yearSponsors and contacts
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Source ClinicalTrials.gov
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