BP1001-A + Paclitaxel for Solid Tumors

Recruiting at 3 trial locations

Overseen By Brian Forbes

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bio-Path Holdings, Inc.

Must not be taking: Investigational agents

Disqualifiers: CNS disease, Cardiac events, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase I, open-label, study of BP1001-A in participants with advanced or recurrent solid tumors. The dose escalation phase will determine the safety and the maximum tolerated dose (MTD) or maximum administered dose (MAD) of BP1001-A as a single agent. After the MTD or MAD of BP1001-A is established, the dose expansion phase will commence and determine the safety, toxicity and response of BP1001-A in combination with paclitaxel.

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

The trial requires that any hormonal therapy directed at the malignant tumor be stopped at least two weeks before starting BP1001-A. Other prior therapies for the tumor must be stopped at least four weeks before the first dose of BP1001-A. Hormone replacement therapy and stable hormonal therapy for prostate, ovarian, or breast cancer can continue.

What data supports the effectiveness of the drug BP1001-A + Paclitaxel for solid tumors?

Paclitaxel, a component of the treatment, has shown effectiveness in treating various advanced or metastatic cancers, including breast, ovarian, and head and neck cancers, even in patients who did not respond to previous treatments. ^{1 2 3 4 5}

What safety data exists for paclitaxel in humans?

Paclitaxel has been used in cancer treatment and is generally safe with premedication, but it can cause side effects like hypersensitivity reactions, low white blood cell counts (neutropenia), nerve damage (neurotoxicity), and hair loss (alopecia). These side effects are often related to the dose and schedule of the treatment. ^{6 7 8 9 10}

What makes the drug BP1001-A + Paclitaxel unique for treating solid tumors?

The combination of BP1001-A with Paclitaxel is unique because it potentially offers a novel mechanism of action by combining a new treatment (BP1001-A) with Paclitaxel, a well-established chemotherapy drug known for its ability to stabilize microtubules and treat various cancers. This combination may enhance the effectiveness of treatment for solid tumors by leveraging the strengths of both components. ^{11 12 13 14 15}

Eligibility Criteria

Adults (≥18 years) with advanced or recurrent solid tumors, such as ovarian, endometrial, fallopian tube cancer, who have no other beneficial treatments available. They must be willing to undergo biopsies and have a life expectancy >3 months. Participants need an ECOG score of 0 or 1 and adequate organ function. Women must not be pregnant and agree to birth control; men also need to use contraception.

Inclusion Criteria

I am willing to have biopsies before and, if needed, after treatment.

My cancer can be measured and has a specific area that can be evaluated.

My ovarian cancer is of a specific cell type.

Exclusion Criteria

You have had a severe allergic reaction to paclitaxel or docetaxel in the past.

I have no lasting side effects worse than mild from previous treatments.

I have HIV with a specific CD4+ T-cell count or active hepatitis B/C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the safety and maximum tolerated dose (MTD) or maximum administered dose (MAD) of BP1001-A as a single agent

4-8 weeks

Dose Expansion

Determine the safety, toxicity, and response of BP1001-A in combination with paclitaxel

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• BP1001-A

Trial Overview The trial is testing BP1001-A alone and combined with paclitaxel in patients with certain solid tumors. It's in phase I where they first find the safest dose for BP1001-A by itself, then see how it works together with paclitaxel regarding safety, toxicity response.

Participant Groups

Group I: BP1001-A monotherapy Experimental Treatment 1 Intervention

Dose escalation of BP1001-A monotherapy

Group II: BP1001-A and Paclitaxel Experimental Treatment 1 Intervention

Dose expansion of selected dose of BP1001-A with paclitaxel

Who Is Running the Clinical Trial?

Bio-Path Holdings, Inc.

Lead Sponsor

Trials

6

Recruited

300+

Findings from Research

In a trial involving 158 HER2-negative metastatic breast cancer patients, cabazitaxel did not significantly improve progression-free survival compared to weekly paclitaxel, with median PFS of 6.7 months for cabazitaxel versus 5.8 months for paclitaxel.

Cabazitaxel was associated with a significantly lower risk of peripheral neuropathy (16.5% vs 54.5% for paclitaxel) and better quality of life scores, indicating it may be a more tolerable option for patients despite similar overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer. Bahl, A., Wilson, W., Ball, J., et al.[2022]

The combination therapy of bevacizumab and paclitaxel (BP regimen) showed a median time to treatment failure of 6.2 months and a median overall survival of 15.4 months in a study of 90 Japanese patients with metastatic breast cancer, indicating its efficacy in real-world settings.

While the BP regimen was generally well tolerated, 31.1% of patients required a dose reduction of paclitaxel, particularly those starting at the higher dose of 90 mg/m2, highlighting the need for careful dose management to minimize adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Real-World Retrospective Cohort Study of Combined Therapy with Bevacizumab and Paclitaxel in Japanese Patients with Metastatic Breast Cancer. Yamada, H., Inoue, K., Nagai, SE., et al.[2022]

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

Paclitaxel has shown significant efficacy as a salvage therapy for various advanced cancers, including non-small cell lung cancer (NSCLC), ovarian, breast, and head and neck cancers, particularly in heavily pretreated patients who did not respond to previous treatments.

Ongoing studies are focused on optimizing paclitaxel's use in combination with other drugs and determining its role in primary therapy, as well as addressing unresolved issues related to its dosage, infusion length, and associated toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the antitumor activity of paclitaxel in clinical trials. Rowinsky, EK.[2017]

In a study of 32 breast cancer patients who had previously failed high-dose chemotherapy, paclitaxel, either alone or combined with epirubicin, showed a 55% overall response rate after 3 courses and a 57% response rate after 6 courses, indicating its efficacy as a salvage treatment.

The median survival for patients receiving these treatments was 27.5 months, although the main side effects were hematologic, including significant neutropenia in 25% of patients, highlighting the need for careful monitoring and management of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage treatment with epirubicin and/or paclitaxel in metastatic breast cancer patients relapsed after high-dose chemotherapy with peripheral blood progenitor cells. Tartarone, A., Sirotovà, Z., Aieta, M., et al.[2022]

Paclitaxel is a highly effective chemotherapeutic agent that works by promoting the polymerization of tubulin, disrupting cell division and leading to cell death, and it is effective against various tumor types including breast, ovarian, and lung cancers.

However, patients may experience significant toxicities such as hypersensitivity reactions and neurotoxicity, which can vary based on the dosage and treatment schedule, and some tumors may develop resistance to the drug through changes in tubulin structure or increased drug efflux.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel in cancer therapy. Mekhail, TM., Markman, M.[2019]

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]

In a study of 15 patients with advanced breast cancer resistant to anthracyclines, paclitaxel administered via a 3-hour intravenous infusion showed an overall response rate of 47%, with three complete responses and four partial responses.

The treatment was generally well-tolerated, with common side effects like neutropenia and hair loss, but these were not clinically concerning, suggesting that higher doses of paclitaxel could be safely explored in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) efficacy in patients with advanced breast cancer resistant to anthracyclines. Gianni, L., Capri, G., Munzone, E., et al.[2015]

Paclitaxel and docetaxel are effective antitumor agents that work by stabilizing microtubules, leading to cell death, but they have different pharmacokinetic profiles; paclitaxel has nonlinear plasma clearance while docetaxel has linear disposition, affecting how their concentrations change with dosage.

Both drugs require premedication to manage side effects, with paclitaxel needing corticosteroids and antihistamines, while docetaxel only requires corticosteroids; their toxic effects differ, with paclitaxel primarily causing neutropenia and peripheral neuropathy, and docetaxel leading to myelosuppression and fluid retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxanes: an overview of the pharmacokinetics and pharmacodynamics. Vaishampayan, U., Parchment, RE., Jasti, BR., et al.[2023]

Paclitaxel is an effective chemotherapy drug that works by stabilizing microtubules, which interrupts cell division, and has shown significant activity against advanced ovarian, breast, and lung cancers in clinical trials.

While paclitaxel is effective, it has notable side effects, particularly neutropenia, which limits dosage, and other adverse effects like hypersensitivity and neurotoxicity, necessitating careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel: a new antineoplastic agent for refractory ovarian cancer. Gregory, RE., DeLisa, AF.[2015]

Paclitaxel has shown significant efficacy in treating various cancers, with response rates of 24%-30% in platinum refractory ovarian cancer and up to 62% in untreated advanced breast cancer, indicating its potential as a key chemotherapy agent.

The drug's unique mechanism of action, along with its ability to be combined with other therapies, suggests it can be effectively used in early-stage disease and has demonstrated superiority over standard treatments in ovarian and lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol®): A new natural product with major anticancer activity. De Furia, MD.[2012]

In a study of 42 metastatic breast cancer patients who had previously been treated with taxanes, nab-paclitaxel demonstrated a 23.8% overall response rate, indicating significant antitumor activity despite prior treatment failures.

Nab-paclitaxel was well tolerated, with most treatment-related side effects being mild to moderate, suggesting a manageable safety profile for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients. Fabi, A., Giannarelli, D., Malaguti, P., et al.[2022]

In a study involving 64 pediatric patients with recurrent or refractory solid tumors, nab-Paclitaxel was found to have a tolerable safety profile, with the maximum tolerated dose (MTD) not reached, but 240 mg/m2 was selected as the recommended phase II dose due to its pharmacokinetics and antitumor activity.

Efficacy results showed that at doses of 210 mg/m2 and above, there were complete and partial responses in a small percentage of patients, with 22% achieving stable disease, indicating potential effectiveness in treating certain pediatric solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. Moreno, L., Casanova, M., Chisholm, JC., et al.[2019]

In a phase II study involving 25 patients with metastatic breast cancer, paclitaxel demonstrated significant efficacy, with 14 patients achieving a major response and a median survival time of 20 months.

Paclitaxel remains effective even in patients who have undergone multiple prior chemotherapy regimens, including those resistant to anthracyclines, although combination therapies can lead to serious side effects like neutropenic fever and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. Hortobagyi, GN., Holmes, FA., Ibrahim, N., et al.[2015]

Combination therapies using paclitaxel with other antineoplastic agents show promise for treating metastatic breast cancer, but optimal dosing and scheduling remain unclear, which complicates their development.

Unexpected toxic interactions between paclitaxel and other drugs have been observed, highlighting the need for careful evaluation of combination therapies in clinical trials before they are used outside of research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review. Holmes, FA.[2015]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

A Real-World Retrospective Cohort Study of Combined Therapy with Bevacizumab and Paclitaxel in Japanese Patients with Metastatic Breast Cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

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

Update on the antitumor activity of paclitaxel in clinical trials. [2017]

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

Salvage treatment with epirubicin and/or paclitaxel in metastatic breast cancer patients relapsed after high-dose chemotherapy with peripheral blood progenitor cells. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Paclitaxel in cancer therapy. [2019]

7. Slovakia pubmed.ncbi.nlm.nih.gov

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

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

Paclitaxel (Taxol) efficacy in patients with advanced breast cancer resistant to anthracyclines. [2015]

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

Taxanes: an overview of the pharmacokinetics and pharmacodynamics. [2023]

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

Paclitaxel: a new antineoplastic agent for refractory ovarian cancer. [2015]

11. Germany pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol®): A new natural product with major anticancer activity. [2012]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. [2019]

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

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. [2015]

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

Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review. [2015]