Onvansertib + Paclitaxel for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining Onvansertib (an experimental treatment) with Paclitaxel (a chemotherapy drug) is safe and effective for treating triple-negative breast cancer that has spread. The trial will explore different doses to find the best balance between effectiveness and safety. Individuals diagnosed with triple-negative breast cancer that cannot be surgically removed or has metastasized, and who are not currently receiving other cancer treatments, might be eligible to participate. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining Onvansertib and Paclitaxel has been tested for safety in patients with advanced triple-negative breast cancer. In one study, about 40% of participants experienced tumor shrinkage, indicating nearly half saw positive results.

This treatment was generally well-tolerated, with most side effects being manageable. Common side effects included nausea and tiredness, typical for cancer treatments. It's important to note that these studies are in the early stages, so the main focus is to ensure safety and determine the best dose.

Paclitaxel is a well-known cancer medication, providing some reassurance about its safety. Onvansertib is newer, but current studies suggest it is safe to use with Paclitaxel. Participants might still experience some side effects, but current research considers the treatment safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Onvansertib combined with Paclitaxel for breast cancer because Onvansertib offers a novel mechanism of action. Unlike traditional treatments that often target hormone receptors or HER2 proteins, Onvansertib is a PLK1 inhibitor, which means it interferes with a protein essential for cancer cell division. This unique approach could potentially enhance the effectiveness of Paclitaxel, a well-established chemotherapy drug, by specifically targeting and disrupting cancer cell replication. This combination holds promise for improving outcomes in breast cancer patients by offering a more targeted attack on cancer cells, potentially leading to better control of the disease.

What evidence suggests that Onvansertib + Paclitaxel might be an effective treatment for triple-negative breast cancer?

Research has shown that combining Onvansertib and Paclitaxel may help treat advanced triple-negative breast cancer (TNBC). In earlier studies, this combination shrank tumors in 40% of patients, meaning four out of ten people experienced significant improvement. The treatment also had manageable side effects. This trial will evaluate the effectiveness of this combination, which targets cancer cells more effectively, offering hope for those with metastatic TNBC. Overall, early results suggest this treatment could be a strong option for advanced TNBC. ^{1 3 4 5 6}

Who Is on the Research Team?

Antonio Giordano, MD,PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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

I am not on any cancer treatments but may be in surveys or studies.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. investors.cardiffoncology.com investors.cardiffoncology.com/news-releases/news-release-details/cardiff-oncology-announces-positive-data-investigator-initiated

Release Details - Cardiff Oncology, Inc. Results from Phase 1b clinical trial evaluating onvansertib + paclitaxel for metastatic triple negative breast cancer demonstrated 40% objective response rate.

2. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/onvansertib-and-paclitaxel-show-promising-results-in-metastatic-tnbc/

Onvansertib and Paclitaxel Show Promising Results in ... Cardiff Oncology announced positive data from a Phase 1b clinical trial of onvansertib combined with paclitaxel for metastatic triple-negative breast cancer ( ...

3. dana-farber.org dana-farber.org/clinical-trials/22-008

A phase 1b/2 study of onvansertib in combination with ... This research is being done to evaluate the safety and effectiveness of Onvansertib in combination with Paclitaxel in triple-negative breast cancer (TNBC)

4. asco.org asco.org/abstracts-presentations/ABSTRACT487788

A phase 1b study of Plk1 inhibitor onvansertib in ... The combination of onvansertib and P demonstrated a safe toxicity profile and promising clinical activity in pretreated mTNBC pts.

5. finance.yahoo.com finance.yahoo.com/news/cardiff-oncology-announces-positive-data-200500776.html

Cardiff Oncology Announces Positive Data from ... Results from Phase 1b clinical trial evaluating onvansertib + paclitaxel for metastatic triple negative breast cancer demonstrated 40% objective response rate.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-07856

Onvansertib in Combination with Paclitaxel for the ... This phase Ib/II trial evaluates the safety, side effects, best dose, and whether onvansertib in combination with paclitaxel works to shrink tumors.