Ovarian NeoplasmsPhase 1/2NCT06620029
BMX-001 + Paclitaxel in Adult Patients With Advanced, Recurrent, Metastatic Ovarian or Endometrial Cancer
A Phase 1/2 study testing BMX-001 and Paclitaxel (Taxol) in people with Ovarian Neoplasms and Endometrial Cancer, Endometrial Neoplasm, run by BioMimetix JV, LLC at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Neoplasms, Endometrial Cancer, Endometrial Neoplasm
- What is being tested?
- BMX-001 and Paclitaxel (Taxol)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2025to 31 Jul 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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)
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- 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.
- For female patients of childbearing potential, the following are exclusion criteria, as applicable:
- 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).
- Severe, active co-morbidity, as defined in protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Duke Cancer Institute
Durham, North Carolina, 27710
Angeles Secord, MD, 919-684-3765, angeles.secord@duke.edu
Angeles Secord, MD
About this study
Official title: 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
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.
Read the detailed description
This clinical trial is a proof-of-concept Phase 1/2 study aimed at establishing the recommended Phase 2 dose (RP2D) of BMX-001 when administered in combination with weekly paclitaxel (PTX) in patients with advanced, metastatic ovarian or endometrial cancer. The rationale for this open-label trial is twofold: (1) response rates to weekly PTX in patients with platinum-resistant ovarian cancer (PROC) are generally low, and when a response is achieved, its duration is often short, necessitating novel therapeutic approaches to improve outcomes; (2) weekly PTX is associated with dose-limiting side effects, particularly chemotherapy-induced peripheral neuropathy (CIPN), which significantly impacts patients quality of life.
The trial includes a dose-finding stage designed to assess the safety and dose-limiting toxicities (DLTs) of the combination treatment. The study will use a Bayesian Optimal Interval (BOIN) design to test the safety of weekly BMX-001 injections in combination with weekly PTX. The goal is to determine if BMX-001 can be safely administered at increasing doses while enhancing both the efficacy of treatment as well as diminishing chemotherapy side effects in patients with recurrent, advanced ovarian and endometrial cancers.
Patients in the dose-escalation phase will receive up to 16 doses over an 8-week period. All participants will receive PTX at a dose of 80 mg/m² on the first day of each weekly cycle. The starting dose of BMX-001 will be 28 mg subcutaneously on the first day of each weekly cycle. Cohorts of three patients will be treated and evaluated for DLTs sequentially. If the starting dose is well-tolerated, subsequent cohorts will escalate to higher doses, with a maximum of 28 mg followed by 28 mg BMX-001 given 4-6 hours apart on the same day each week. Should any patients at Dose Level 1 experience DLTs, the dose will be de-escalated according to the BOIN design to Dose Level -1 (14 mg/week), and if necessary, further to Dose Level -2 (7 mg/week), which is the final de-escalation dose group.
Upon completion of the dose-finding phase, an expansion cohort will be enrolled at the RP2D. The study will enroll up to 27 patients in this trial. The primary outcome measure is to establish the RP2D of BMX-001 in combination with PTX. Secondary outcomes include evaluation of preliminary efficacy based on objective response rate (ORR) using RECIST v 1.1 per investigator assessment endpoints and obtaining a description of patient-reported outcomes of health related quality of life (HRQoL) quality of life (QoL) using FACT/GOG-NTX Questionnaire and monofilament testing.
Other outcome measures to be assessed in all patients include characterization of the pharmacokinetic profile of BMX-001 when delivered in combination with PTX in recurrent ovarian or endometrial cancer and also to assess correlations between B cell lymphoma/leukemia 2 (BCL2), Nrf2, TNF-alpha, and NFkB RNA and protein expression and activation, ctDNA, and clinical responses. This initial single arm trial is limited to 27 subjects based on the funds available in this SBIR. In spite of the small sample size, the study expects to obtain sufficient data to enable design a subsequent randomized trial that would meet registration requirements
- Being tested
- BMX-001, Paclitaxel (Taxol)
- Keywords
- BMX-001 plus Paclitaxel
- Medical subject headings
- Ovarian Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMX-001Drug
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: BMX-001; Drug: Paclitaxel (Taxol) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2024
- Study start1 Apr 2025 (estimated)
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Dose finding stage followed by an expansion cohort.
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioMimetix JV, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Crapo, MD, Study director, BioMimetix JV, LLCAngeles Secord, Principal investigator, Duke Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06620029
- Sponsor's protocol ID
- BMX-GyCa-001
- Status last verified
- Sep 2024
- First submitted
- 18 Sep 2024
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided