BMX-001 + Paclitaxel for Ovarian Cancer

Overseen By Sara Penchev

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: BioMimetix JV, LLC

Must not be taking: Corticosteroids, Anticancer therapy

Disqualifiers: Peripheral neuropathy, CNS metastases, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

27 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must wait at least 28 days after stopping any prior anticancer or hormonal therapy before starting the trial treatment.

What data supports the effectiveness of the drug BMX-001 + Paclitaxel for ovarian cancer?

Paclitaxel has been shown to be effective in patients with ovarian cancer, especially those who have not responded to platinum-based treatments. It is often used in combination with other drugs to improve outcomes in ovarian cancer patients. ^{1 2 3 4 5}

Is the combination of BMX-001 and Paclitaxel safe for humans?

Paclitaxel, a drug used in combination with BMX-001, has been studied for safety in humans. It can cause hypersensitivity reactions, but these are reduced with premedication. The main side effect is neutropenia (a low level of white blood cells), which can increase infection risk. ^{4 5 6 7 8}

What makes the drug BMX-001 + Paclitaxel unique for treating ovarian cancer?

The combination of BMX-001 with Paclitaxel is unique because BMX-001 is a novel component that may enhance the effectiveness of Paclitaxel, which is already a standard treatment for ovarian cancer, especially in cases where other platinum-based therapies have failed. This combination could potentially offer a new approach for patients who have not responded to existing treatments. ^{2 3 4 8 9}

What is the purpose of 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.

Research Team

Angeles A. Secord

Principal Investigator

Duke Cancer Institute

James Crapo, MD

Principal Investigator

BioMimetix JV, LLC

Eligibility Criteria

This trial is for adults with advanced, recurrent, metastatic ovarian or endometrial cancer who have faced issues with chemotherapy resistance and nerve damage from previous treatments. Specific eligibility criteria are not provided but typically include factors like health status and prior treatment history.

Inclusion Criteria

My bone marrow is working well.

My liver is working well.

I can perform all my usual activities without assistance.

Exclusion Criteria

I have not had a serious infection requiring IV antibiotics or hospital stay in the last week.

I have moderate numbness or pain in my hands or feet.

I have a serious heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-finding

Dose-finding stage to assess safety and dose-limiting toxicities of BMX-001 and PTX combination

8 weeks

Weekly visits for dose administration and monitoring

Treatment

Participants receive BMX-001 and PTX weekly to evaluate safety, tolerability, and efficacy

48 weeks

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Every 12 weeks until disease progression or study termination

Treatment Details

Interventions

• BMX-001
• Paclitaxel

Trial Overview The study tests BMX-001 in combination with the chemotherapy drug Paclitaxel (Taxol). It aims to find a safe dosage that enhances tumor control while reducing side effects, especially nerve damage caused by Taxol. The trial will also monitor how well tumors respond to this treatment combo.

Participant Groups

Group I: BMX-001 + PTX Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

BioMimetix JV, LLC

Lead Sponsor

Trials

11

Recruited

700+

Findings from Research

Inhibiting Src family and Abl kinases using siRNAs or dasatinib significantly enhances the sensitivity of ovarian cancer cells to paclitaxel, as demonstrated in both cell cultures and HEY xenograft models.

The mechanism involves the induction of p27(Kip1), which promotes apoptosis by suppressing Bcl-2 and Cdk1 expression, leading to increased effectiveness of paclitaxel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. Le, XF., Mao, W., He, G., et al.[2021]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Paclitaxel has been established as an effective treatment for newly diagnosed ovarian cancer patients, leading to its incorporation into primary chemotherapy regimens, particularly in combination with cisplatin as the new standard in the U.S.

Ongoing clinical trials are exploring various strategies to optimize paclitaxel-based chemotherapy, including comparisons of different platinum-based drugs and infusion schedules, as well as evaluating high-dose therapies with stem cell support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced ovarian cancer: current status and future directions. Ozols, RF., Vermorken, JB.[2015]

Paclitaxel demonstrated a 22% objective response rate in women with platinum-refractory ovarian cancer, indicating it can be an effective treatment option for this challenging condition.

While the treatment had an acceptable safety profile, with leukopenia being the most common severe toxicity (78% of patients), there were also treatment-related deaths (1.5%), highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103. Trimble, EL., Adams, JD., Vena, D., et al.[2017]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

Paclitaxel is a cytotoxic drug that belongs to the taxane group and is specifically approved for treating metastatic ovarian carcinoma after standard platinum-based therapies have not been effective.

It represents a new treatment option for patients with advanced ovarian cancer, providing an alternative when traditional therapies fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel for ovarian cancer. [2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced ovarian cancer: current status and future directions. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103. [2017]

5. Netherlands pubmed.ncbi.nlm.nih.gov

[Favorable results of paclitaxel (Taxol) in patients with ovary carcinoma pretreated with platinum]. [2015]

6. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

7. Thailand pubmed.ncbi.nlm.nih.gov

Treatment outcomes of paclitaxel for refractory or recurrent epithelial ovarian cancer patients in Thailand. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Paclitaxel for ovarian cancer. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer. [2021]