Onvansertib + Paclitaxel for Breast Cancer

Recruiting at 2 trial locations

Overseen By Antonio Giordano, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Antonio Giordano, MD

Must not be taking: Strong CYP3A4 inhibitors/inducers

Disqualifiers: Pregnancy, Breastfeeding, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety and effectiveness of combining Onvansertib, an experimental drug, with Paclitaxel, a chemotherapy drug, in patients with advanced triple-negative breast cancer. The goal is to find the best dose of Onvansertib and see if this combination can help treat this aggressive form of cancer.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does prohibit the use of strong inhibitors or inducers of CYP3A4 and medications that prolong the QT/QTc interval. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot be on any other cancer therapy and must avoid medications that prolong the QT/QTc interval or are strong inhibitors/inducers of CYP3A4. If you are on such medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug combination Onvansertib and Paclitaxel for breast cancer?

Paclitaxel has been shown to be effective in treating metastatic breast cancer, and when combined with bevacizumab, it has improved progression-free survival, meaning patients lived longer without the cancer getting worse. Although Onvansertib is not specifically mentioned, the effectiveness of paclitaxel in similar combinations suggests potential benefits. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Onvansertib + Paclitaxel for breast cancer?

Paclitaxel, a component of the treatment, has shown effectiveness in treating metastatic breast cancer, especially when combined with other drugs like bevacizumab, leading to improved progression-free survival (the time during which the cancer does not get worse). However, the specific combination of Onvansertib and Paclitaxel for breast cancer lacks direct evidence in the provided research. ^{1 2 3 4 5}

Is the combination of Onvansertib and Paclitaxel safe for humans?

Paclitaxel, used alone or in combination with other drugs, has been generally well tolerated in breast cancer patients, with common side effects including febrile neutropenia (fever with low white blood cell count), headache, and peripheral neuropathy (nerve damage causing pain or numbness). There is no specific safety data available for Onvansertib in combination with Paclitaxel, but Paclitaxel has shown a favorable safety profile in various studies. ^{6 7 8 9 10}

Is the combination of Onvansertib and Paclitaxel safe for humans?

Paclitaxel has been studied extensively and is generally well tolerated, with common side effects including febrile neutropenia (fever with low white blood cell count) and peripheral neuropathy (nerve damage causing tingling or numbness). While Onvansertib's specific safety data in combination with Paclitaxel is not detailed here, Paclitaxel has been safely combined with other treatments in breast cancer studies. ^{6 7 8 9 10}

What makes the drug combination of Onvansertib and Paclitaxel unique for breast cancer treatment?

The combination of Onvansertib and Paclitaxel is unique because Onvansertib is a novel drug that may enhance the effectiveness of Paclitaxel, a well-established chemotherapy drug, by targeting specific cancer cell mechanisms, potentially offering a new option for patients with breast cancer who have limited treatment choices. ^{1 4 11 12 13}

What makes the drug combination of Onvansertib and Paclitaxel unique for breast cancer treatment?

The combination of Onvansertib and Paclitaxel is unique because Onvansertib is a novel drug that may enhance the effectiveness of Paclitaxel, which is already used in breast cancer treatment. Onvansertib works by targeting specific proteins involved in cancer cell division, potentially offering a new mechanism of action compared to existing treatments. ^{1 4 11 12 14}

Research Team

Antonio Giordano, MD,PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with advanced triple-negative breast cancer (TNBC) that has spread, who are in good physical condition and haven't had more than three chemotherapy treatments for metastatic disease. They must not be pregnant or breastfeeding, have no severe allergies to paclitaxel, and agree to use contraception during the study.

Inclusion Criteria

My breast cancer is triple negative.

I am 18 years old or older.

I agree to use birth control or avoid pregnancy during and for 6 months after the study.

Exclusion Criteria

I have had more than 3 chemotherapy treatments for my advanced cancer.

I cannot or do not want to take pills.

I will be taking medications that can affect my heart's rhythm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Onvansertib in combination with Paclitaxel. Phase 1b involves dose escalation to determine the maximum tolerated dose, followed by Phase 2 with a fixed dose.

24 weeks

Every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

Treatment Details

Interventions

• Onvansertib
• Paclitaxel

Trial Overview The trial is testing the combination of Onvansertib with Paclitaxel to see if it's safe and effective against TNBC that has metastasized. Participants will receive both drugs; Onvansertib is taken orally while Paclitaxel is given intravenously.

Participant Groups

Group I: DOSE EXPANSION RP2D ONVANSERTIB + PACLITAXEL Experimental Treatment 2 Interventions

The study is divided into three time periods: a screening period; a treatment period; and a post-treatment follow-up period. The names of the study interventions involved in this study are: * Onvansertib * Paclitaxel

Group II: DOSE ESCALATION ONVANSERTIB + PACLITAXEL Experimental Treatment 2 Interventions

In the phase 1b, dose escalation/de-escalation will be managed using a BOIN design to identify the RP2D. The study is divided into three time periods: a screening period; a treatment period; and a post-treatment follow-up period. The names of the study interventions involved in this study are: * Onvansertib * Paclitaxel

Onvansertib is already approved in United States, European Union for the following indications:

Approved in United States as Onvansertib for:

• Acute Myeloid Leukemia (AML) - Orphan Drug Designation

Approved in European Union as Onvansertib for:

• Acute Myeloid Leukemia (AML) - Orphan Drug Designation

Who Is Running the Clinical Trial?

Antonio Giordano, MD

Lead Sponsor

Trials

1

Recruited

50+

Cardiff Oncology

Industry Sponsor

Trials

12

Recruited

650+

Findings from Research

A panel of expert oncologists reached consensus that the combination of bevacizumab and paclitaxel is effective as a first-line treatment for HER2-negative metastatic breast cancer, showing a significant progression-free survival benefit compared to paclitaxel alone.

Despite the absence of an overall survival benefit in clinical trials, the panel acknowledged the regimen's effectiveness and safety based on real-world data, although opinions varied on its use in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Delphi consensus and open debate on the role of first-line bevacizumab for HER2-negative metastatic breast cancer. Puglisi, F., Bisagni, G., Ciccarese, M., et al.[2017]

Paclitaxel (Taxol) is a significant new chemotherapy drug for breast cancer, showing promise in both single-agent and combination treatments.

Ongoing research at Memorial Sloan-Kettering Cancer Center aims to optimize the use of paclitaxel in various treatment settings, including metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. Seidman, AD., Hudis, CA., Fennelly, D., et al.[2015]

In a phase 3 trial involving 564 patients with HER2-negative metastatic breast cancer, combining bevacizumab with paclitaxel resulted in significantly better progression-free survival and higher objective response rates compared to combining bevacizumab with capecitabine.

The trial did not meet the non-inferiority criterion for overall survival between the two treatment regimens, indicating that while paclitaxel showed better efficacy, the overall survival results remain inconclusive pending final analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lang, I., Brodowicz, T., Ryvo, L., et al.[2020]

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]

A 68-year-old woman with metastatic breast cancer who was resistant to taxane treatment showed a partial response when treated with a combination of weekly paclitaxel and bevacizumab, indicating potential effectiveness of this regimen in taxane-resistant cases.

This case suggests that combining bevacizumab with taxanes may provide a valuable treatment option for patients with metastatic breast cancer who have developed resistance to standard taxane therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-resistant advanced recurrent breast cancer: a case of partial response due to addition of bevacizumab to paclitaxel therapy: a case report. Ishizuna, K., Ninomiya, J., Kojima, M., et al.[2021]

The combination of Durvalumab and Paclitaxel in treating metastatic triple-negative breast cancer (TNBC) was found to be safe, with no dose-limiting toxicities reported in a trial involving 14 patients, although 71% experienced some adverse events, primarily headaches and peripheral neuropathy.

The treatment showed minimal efficacy, with a confirmed objective response rate in 5 patients and a median progression-free survival of 5 months, suggesting that while the combination is safe, further research is needed to improve outcomes in TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer. Ghebeh, H., Al-Sayed, A., Eiada, R., et al.[2021]

In a study of 242 breast and gynecological cancer patients, the addition of Helixor® VA therapy to targeted therapies did not negatively impact the safety profile of the treatments, indicating it can be safely combined with standard therapies.

Patients receiving the combination therapy showed no adverse events and a trend towards better adherence to targeted therapy, suggesting that Helixor® VA may enhance the overall treatment experience without increasing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Targeted and Helixor®Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study. Schad, F., Thronicke, A.[2023]

Paclitaxel has shown promising efficacy in treating stage IV breast cancer, with overall response rates ranging from 44% to 62% in phase II trials, indicating it can be an effective option for patients with limited prior therapy.

The treatment is generally well tolerated, with febrile neutropenia being the most common side effect, and it has demonstrated safety and efficacy even in patients with extensive prior therapy, achieving response rates of 36% in those with two prior treatments and 21% in those with three or more.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent use of Taxol (paclitaxel) in breast cancer. Seidman, AD.[2016]

A new regimen combining doxorubicin and paclitaxel has been developed that is both well-tolerated and highly effective, utilizing bolus administration of doxorubicin and a 3-hour infusion of paclitaxel, overcoming previous schedule-dependent toxicity issues.

Paclitaxel has shown promising results when combined with fluorouracil and folinic acid in patients with extensive prior chemotherapy, and adding mitoxantrone to this combination appears to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-based combination chemotherapy for breast cancer. Hortobagyi, GN.[2015]

The combination of sunitinib and paclitaxel was well tolerated in a study of 22 patients with locally advanced or metastatic breast cancer, with common side effects including fatigue, dysgeusia, and diarrhea.

Out of 18 patients with measurable disease, 38.9% achieved objective responses, suggesting preliminary antitumor activity, particularly in patients with triple-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer. Kozloff, M., Chuang, E., Starr, A., et al.[2021]

In a study of seven patients with HER2-positive metastatic breast cancer, the combination of bevacizumab and paclitaxel after multiple HER2-targeted therapies showed promising results, with four patients achieving a partial response.

The treatment resulted in a median progression-free survival of 10 months, suggesting that this combination therapy could be an effective option when standard HER2-targeted therapies are no longer effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential effectiveness of combining bevacizumab with paclitaxel for treating HER2-positive metastatic breast cancer. Hamada-Nishimoto, M., Kang, Y., Shiraki, E., et al.[2022]

Combination therapies using paclitaxel with non-anthracycline agents have shown promising response rates between 40% to 80% and median time to progression exceeding 6 months in phase II and III studies.

Further research through prospective, randomized phase III trials is needed to confirm the benefits of these combinations over older treatments, particularly regarding quality of life, response rates, and survival in metastatic breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. Perez, EA.[2015]

The AVALUZ trial demonstrated that the combination of bevacizumab, gemcitabine, and paclitaxel resulted in a median progression-free survival of 12.3 months and a median overall survival of 27.4 months in previously untreated HER-2 negative breast cancer patients.

The treatment was generally well tolerated, with manageable adverse events, and showed that baseline circulating tumor cells and angiotensin type 1 receptor expression could predict patient responses and progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. Salvador, J., Manso, L., de la Haba, J., et al.[2022]

The combination of paclitaxel and vinorelbine was effective as a first-line treatment for untreated patients with metastatic lung adenocarcinoma, with a response rate of 50% and a median survival of 10 months based on a study of 54 patients.

While myelotoxicity was a common side effect affecting 87% of patients, severe neutropenia (grade 4) occurred in only 14.8%, indicating that the treatment regimen was manageable and did not require dose reductions for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study. Stathopoulos, GP., Veslemes, M., Georgatou, N., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

A Delphi consensus and open debate on the role of first-line bevacizumab for HER2-negative metastatic breast cancer. [2017]

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

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. [2015]

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

Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. [2020]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Paclitaxel-resistant advanced recurrent breast cancer: a case of partial response due to addition of bevacizumab to paclitaxel therapy: a case report. [2021]

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

Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Combined Targeted and Helixor®Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study. [2023]

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

Single-agent use of Taxol (paclitaxel) in breast cancer. [2016]

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

Paclitaxel-based combination chemotherapy for breast cancer. [2015]

10. England pubmed.ncbi.nlm.nih.gov

An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer. [2021]

11. Singapore pubmed.ncbi.nlm.nih.gov

Potential effectiveness of combining bevacizumab with paclitaxel for treating HER2-positive metastatic breast cancer. [2022]

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

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. [2015]

13. Italy pubmed.ncbi.nlm.nih.gov

Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. [2022]

14. Greece pubmed.ncbi.nlm.nih.gov

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study. [2018]