What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as Paclitaxel and kinase inhibitors like Onvansertib, have distinct side effect profiles. Paclitaxel often causes neuropathy, myelosuppression, alopecia, and hypersensitivity reactions. Kinase inhibitors typically result in fatigue, nausea, diarrhea, and potential cardiovascular issues. Patients undergoing these treatments should be closely monitored for these side effects to manage them effectively.

What prior FDA approvals exist?

Paclitaxel, a microtubule stabilizer, has been FDA-approved for the treatment of breast cancer and is commonly used in various chemotherapy regimens. Other microtubule stabilizers like docetaxel have also received FDA approval for breast cancer. While Onvansertib, a PLK1 inhibitor, is currently being studied, there are no specific FDA-approved PLK1 inhibitors for breast cancer treatment at this time. However, PLK1 inhibitors are being explored in clinical trials for their potential efficacy in various cancers, including breast cancer.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: 1) CDK4/6 inhibitors such as Abemaciclib, which have shown efficacy in hormone receptor-positive breast cancer. 2) Immune checkpoint inhibitors like Pembrolizumab, particularly for triple-negative breast cancer. 3) PARP inhibitors such as Olaparib for patients with BRCA mutations. 4) Antibody-drug conjugates like Trastuzumab Deruxtecan for HER2-positive breast cancer. These therapies represent advancements in targeted and immunotherapy approaches.

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Cell Cycle Inhibitor

Onvansertib + Paclitaxel for Breast Cancer

Phase 1 & 2

Recruiting

Led By Antonio C Giordano, MD, PhD

Research Sponsored by Antonio Giordano, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically-confirmed triple negative breast cancer (defined as ER ≤ 10%, PR ≤ 10%, Her-2-neu negative per ASCO/CAP 2018 guidelines: 0-1+ by IHC or FISH-negative)

Age ≥ 18 years

Must not have

Unable or unwilling to swallow study drug

Planned concomitant use of medications known to prolong the QT/QTc interval

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every 8 weeks until disease progression, in average 24 weeks

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include allergic reactions, nerve damage (neuropathy), fatigue, digestive issues like nausea or diarrhea, low blood cell counts leading to increased infection risk or bleeding problems, liver function changes, and muscle aches.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is triple negative.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My breast cancer is advanced, cannot be surgically removed, and may have spread.

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My blood tests show my organs are functioning well.

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I cannot be on hormone therapy if my cancer is hormone receptor positive.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot or do not want to take pills.

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

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I am not taking strong CYP3A4 inhibitors or inducers.

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I have risk factors for a specific heart rhythm issue or low potassium levels.

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I do not have any serious ongoing illnesses that would affect my participation.

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

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I am not pregnant or breastfeeding.

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I have significant fluid buildup in my abdomen or around my lungs.

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I have not had major surgery in the last 6 weeks.

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My cancer returned or worsened within 6 months after my last taxane-based treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ every 8 weeks until disease progression, in average 24 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~every 8 weeks until disease progression, in average 24 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and every 8 weeks until disease progression, in average 24 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-Limiting Toxicity (DLT)-Phase Ib

Therapeutic procedure

Overall Response Rate (ORR) Phase II

Secondary study objectives

AUC-Phase Ib

Cmax-Phase Ib

Incidence of Grade 3 or Higher Treatment-Related Toxicity-Phase II

+1 more

Side effects data

From 2021 Phase 1 & 2 trial • 72 Patients • NCT03303339

38%

Febrile neutropenia

31%

Hypokalaemia

28%

Diarrhoea

28%

Stomatitis

25%

Fatigue

22%

Nausea

22%

Epistaxis

19%

Oedema peripheral

19%

Platelet count decreased

19%

Alopecia

16%

Hypophosphataemia

16%

Acute myeloid leukaemia

16%

Sepsis

16%

Dyspnoea

16%

Cough

16%

Hypoalbuminaemia

13%

Hypoxia

13%

Lung infection

13%

Anaemia

13%

Rash maculo-papular

13%

Rash

13%

Hypocalcaemia

13%

Arthralgia

13%

Hypertension

13%

Hypotension

Electrocardiogram QT prolonged

Syncope

Pneumonia

Cellulitis

Headache

Abdominal pain upper

Oral pain

Staphylococcal infection

Urinary tract infection

Hypomagnesaemia

Dizziness

Oropharyngeal pain

Petechiae

Decreased appetite

Alanine aminotransferase increased

Abdominal pain

Escherichia bacteraemia

Blood creatine increased

Mucosal inflammation

Hyperbilirubinaemia

Pleural effusion

Vomiting

Ear pain

Fluid overload

Dry skin

Lower gastrointestinal haemorrhage

Dry mouth

Oral candidiasis

Neuropathy peripheral

Fall

Pyrexia

Nasal congestion

Ecchymosis

Blood alkaline phosphatase

Insomnia

Pain in extremity

Haematemesis

Odynophagia

Proctalgia

Staphylococcal bacteraemia

Bacteraemia

Pneumonia fungal

Pruritus

Dermatitis contact

Purpora

Non-cardiac chest pain

Hyperkalaemia

Hypercalcaemia

Flank pain

Aspartate aminotransferase increased

Neutrophil count decreased

Blood bilirubin increased

Pleuritic pain

Haematoma

Conjunctival haemorrhage

Hyperglycaemia

Myalgia

Back pain

Atrial fibrillation

Tumour lysis syndrome

Mallory-Weiss syndrome

Upper gastrointestinal haemorrhage

Pain

Respiratory failure

Rash pruritic

Musculoskeletal pain

Face oedema

Hyponatraemia

Contusion

Septic shock

Candida infection

Granulicatella bacteraemia

Kidney infection

Pancytopenia

Colitis

Melaena

Constipation

Transfusion reaction

Dysgeusia

Dyspnoea exertional

Wheezing

Neutropenia

Weight decreased

Anxiety

Eye pruritus

White blood cell count decreased

Neutropenic colitis

Mental status changes

Chills

Sinus tachycardia

Haemoptysis

Aphasia

100%

80%

60%

40%

20%

Study treatment Arm

Phase 2: Onvansertib 60 mg/m^2 + Decitabine

Phase 1b: Onvansertib 90 mg/m^2 + Decitabine

Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 12 mg/m^2 + Decitabine

Phase 1b: Onvansertib 40 mg/m^2 + Decitabine

Phase 1b: Onvansertib 60 mg/m^2 + Decitabine

Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 18 mg/m^2 + Decitabine

Phase 1b: Onvansertib 27 mg/m^2 + Decitabine

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Onvansertib

2017

Completed Phase 2

~220

Paclitaxel

2011

Completed Phase 4

~5370

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Onvansertib, a PLK1 inhibitor, disrupts cell division by inhibiting Polo-like kinase 1, leading to the death of rapidly dividing cancer cells. Paclitaxel, a microtubule stabilizer, prevents the disassembly of microtubules, inhibiting mitosis and inducing apoptosis in cancer cells. These mechanisms are vital for breast cancer patients as they offer targeted approaches to halt cancer cell proliferation and improve treatment efficacy.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Dasatinib : a novel therapy for breast cancer?