Onvansertib + Paclitaxel for Breast Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Antonio Giordano, MD
No Placebo Group
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.
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.
12345Is 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.
678910What 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.
14111213Eligibility 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.
+8 more
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.
+16 more
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: DOSE EXPANSION RP2D ONVANSERTIB + PACLITAXELExperimental Treatment2 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 + PACLITAXELExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
Beth Israel Deaconness Medical CenterBoston, MA
Dana-Farber Cancer InstituteBoston, MA
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Who Is Running the Clinical Trial?
Antonio Giordano, MDLead Sponsor
Cardiff OncologyIndustry Sponsor
References
A Delphi consensus and open debate on the role of first-line bevacizumab for HER2-negative metastatic breast cancer. [2017]To gain consensus on the role of bevacizumab plus paclitaxel as first-line treatment for HER2-negative metastatic breast cancer, a panel of expert oncologists experienced in treating patients with metastatic breast cancer in Italy participated in a Delphi consensus study. The panel reached a full consensus on the efficacy of bevacizumab plus paclitaxel and the clinical meaningfulness of the progression-free survival benefit compared with paclitaxel alone, despite the lack of an overall survival effect in clinical trials. The participants agreed that real-world data support the effectiveness and well-defined safety profile of the regimen. Views on the use of bevacizumab plus paclitaxel in specific patient populations were not unanimous and clinical judgment remains important. Nevertheless, a high level of agreement was reached.
Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. [2015]Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is the most important new cytotoxic agent to be introduced for the management of breast cancer in many years. During this decade, investigators at Memorial Sloan-Kettering Cancer Center have conducted multiple clinical and laboratory investigations aimed at optimally integrating this agent into therapeutic strategies for breast cancer. These studies address both single-agent and combination regimens in the metastatic and adjuvant settings. This report will review previous results, but focus on active studies and future avenues of research.
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]Randomised phase 3 trials in metastatic breast cancer have shown that combining bevacizumab with either paclitaxel or capecitabine significantly improves progression-free survival and response rate compared with chemotherapy alone but the relative efficacy of bevacizumab plus paclitaxel versus bevacizumab plus capecitabine has not been investigated. We compared the efficacy of the two regimens.
Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]Paclitaxel has shown activity in metastatic breast cancer, including anthracycline-resistant breast cancer. The efficacy, toxicity and optimal scheduling of the combination of the two drugs needs to be defined.
Paclitaxel-resistant advanced recurrent breast cancer: a case of partial response due to addition of bevacizumab to paclitaxel therapy: a case report. [2021]Paclitaxel plus bevacizumab have shown a high response rate and prolonged progression-free survival in metastatic breast cancer patients. However, overall survival was not prolonged. Thus, no conclusion has been made on the effectiveness of bevacizumab. In our report, taxane plus bevacizumab were used to treat a metastatic breast cancer patient with taxane resistance, and a good therapeutic result was obtained.
Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer. [2021]Therapeutic anti-PD-L1 antibodies are safe as a monotherapy, albeit with minimal efficacy in triple-negative breast cancer (TNBC). This trial aimed to test the safety and efficacy of Durvalumab and Paclitaxel in metastatic TNBC. In this open-label, one-arm trial, five cycles of weekly paclitaxel were delivered intravenously (IV) concurrent with Durvalumab that was given IV every 2 weeks. The combination was preceded by one cycle of paclitaxel alone, for immunological priming, followed by Durvalumab solo until disease progression or unacceptable toxicity. Between 2017 and 2019, 14 patients received at least one cycle of the combination therapy. The therapy was safe with no-dose limiting toxicity, except one case of skin lesions. Adverse events (AEs) were reported in 71% of patients, and there was no death due to the combination therapy. Regardless of grade, the most common AEs were headache and peripheral neuropathy, as each happened in four patients (29%), followed by fatigue and skin rash in three patients (21%) each. Grade 3/4 AEs were experienced by three patients (21%), with the most common being headache and anemia, which happened in two patients (14%). The confirmed objective response rate (ORR) was observed in five patients with a median duration of 10.0 months. Median Progression-free survival (PFS) and overall survival (OS) were 5 and 20.7 months, respectively. The combination of Durvalumab and Paclitaxel is safe, leaving room for additional agents. This is the first report on the combination of Durvalumab and Paclitaxel in the treatment of TNBC (NCT02628132).
Safety of Combined Targeted and Helixor®Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study. [2023]Label="BACKGROUND">Newer personalized medicines including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have been shown to improve the survival of breast and gynaecological cancer patients. However, efficacy outcomes may be ham5pered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies have suggested that add-on mistletoe (Viscum album L., VA) improves the quality of life and ameliorates the cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy compared to targeted therapy alone in breast and gynecological cancer patients.
Single-agent use of Taxol (paclitaxel) in breast cancer. [2016]The search for new active agents and strategies to improve the prognosis for patients with stage IV breast cancer has led to examination of paclitaxel. Several clinical trials have been undertaken to determine its optimal use and clarify its role in the treatment of breast cancer and other malignancies. Several phase II trials involving breast cancer patients with limited prior therapy have yielded overall response rates (complete response and partial response) of 44% to 62% among women receiving paclitaxel. Treatment was generally well tolerated, with febrile neutropenia the most common side effect. An interim analysis of the European-Canadian Randomized Trial in Metastatic Breast Cancer demonstrated safety and efficacy of paclitaxel in a multicenter setting. Among the 234 patients evaluable for response, 29% (34/117) responded at 175 mg/m2 paclitaxel and 22% responded (26/117) at 135 mg/m2. Treatment was well tolerated at both dose levels; responses continue to evolve in patients who remain on study. Among patients with extensive prior therapy (> 2 prior regimens for stage IV disease), paclitaxel also has demonstrated safety and efficacy. At Memorial Sloan-Kettering Cancer Center, responses were noted among 36% of patients who had received two prior treatments and 21% of those who had received 3 or more. Paclitaxel was administered at 200 mg/m2 plus G-CSF. Other studies involving heavily pretreated patients yielded overall response rates as high as 53%. The concerns about cross-resistance between paclitaxel and doxorubicin (or other agents for which resistance is thought to be at least partly due to P-glycoprotein-mediated pleiotropic drug resistance) also are addressed.
Paclitaxel-based combination chemotherapy for breast cancer. [2015]Clinical trials to develop paclitaxel (Taxol)-containing combinations started in 1992 with several approaches to combine doxorubicin and paclitaxel. Schedule-dependent toxicity limited doses in the initial trials, although antitumor activity was high. More recently, a well-tolerated, highly effective doxorubicin/paclitaxel regimen was developed with the use of bolus anthracycline administration and a 3-hour infusion of paclitaxel. Combinations of paclitaxel with cisplatin have provided mixed results. Paclitaxel combined with fluorouracil (5-FU) and folinic acid proved effective in patients with extensive prior chemotherapy; the addition of mitoxantrone (Novantrone) to this combination was feasible, well tolerated, and possibly enhanced the efficacy of paclitaxel and 5-FU. Combinations of paclitaxel with cyclophosphamide (Cytoxan, Neosar), vinorelbine (Navelbine), edatrexate, and radiation continue in clinical development.
An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer. [2021]Sunitinib has shown single-agent activity in patients with previously treated metastatic breast cancer (MBC). We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC.
Potential effectiveness of combining bevacizumab with paclitaxel for treating HER2-positive metastatic breast cancer. [2022]Although various first- to third-line HER2-targeted therapies have been established, the optimal sequence after third-line therapy has not been determined yet. Here, we describe seven patients with HER2-positive metastatic breast cancer who underwent bevacizumab (BV) and paclitaxel (PTX) combination therapy after several HER2-targeted therapies. Re-biopsy of metastatic sites was performed on four patients during the treatment prior to BV + PTX; three patients presented the same HER2-positive status as that of the primary tumor and two of whom achieved partial response. Four of seven patients achieved partial response and a 10-month median progression-free survival. Therefore, bevacizumab combined with paclitaxel is potentially effective in the treatment of HER2-positive metastatic breast cancer, if standard HER2-targeted therapy fails.
Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. [2015]The results of several phase II and some phase III studies are now available in which the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and nonanthracycline agents are evaluated. The studies demonstrate the activity and feasibility of these combinations, which achieved response rates of 40% to 80% and median time to progression that exceeded 6 months. The potential role of these combinations compared with older non-paclitaxel-containing regimens, in improving quality of life, response rate, and survival in patients with metastatic breast cancer, however, await the results of prospective, randomized phase III trials. The next logical step, depending on the results of planned comparative trials, is to incorporate these combinations in the neoadjuvant and adjuvant settings.
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]Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited.