Loading clinical trials...

Onalespib and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer | Clinical Trials | Clareo Health

TERMINATEDPHASE1

Onalespib and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer

Phase 1b Study of HSP90 Inhibitor, AT13387 (Onalespib) in Combination With Paclitaxel in Patients With Advanced, Triple Negative Breast Cancer

NCT02474173•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase Ib trial studies the side effects and best dose onalespib when given together with paclitaxel in treating patients with triple negative breast cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Onalespib works by blocking proper processing of proteins that are important for cancer growth. This results in inability of these proteins to work properly. Paclitaxel kills breast cancer cells by interfering with their ability to divide. Giving onalespib together with paclitaxel may be better than giving either one alone in treating patients with breast cancer.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose (RP2D) of onalespib (AT13387) in combination with paclitaxel in patients with advanced triple negative breast cancer (TNBC). II. To determine the toxicity profile (based on Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\]5.0) of the combination of AT13387 in combination with paclitaxel in patients with advanced TNBC. SECONDARY OBJECTIVES: I. To determine the effect of AT13387 on pharmacokinetics of paclitaxel in the study patient population. II. To determine the effect of paclitaxel on pharmacokinetics of AT13387 in the study patient population. III. To observe anti-tumor activity determining the overall response rate (partial response + complete response), response duration and progression-free survival. OUTLINE: This is a dose-escalation study of onalespib. SAFETY RUN-IN: Patients receive onalespib intravenously (IV) over 1 hour on day -7. TREATMENT: Patients receive paclitaxel IV over 60 minutes on day 1, 8, and 15. Patients also receive onalespib IV over 1 hour beginning on days 8 and 15 of cycle 1 and on days 1, 8, and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have histologically confirmed measurable or unmeasurable advanced or metastatic breast cancer for which standard curative measures do not exist or are no longer effective
•* Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
•Primary and/or metastatic breast tumor must be negative for over-expression of estrogen and progesterone receptors; patients with weak estrogen receptor and/or progesterone receptor expression (\< 10% on immunohistochemistry \[IHC\]) will be eligible
•Primary and/or metastatic breast tumor must be negative for human epidermal growth factor receptor (HER-2/neu) over-expression based on immunohistochemistry (IHC) (0 or 1+, 2+ if fluorescence in-situ hybridization \[FISH\] test is negative) or FISH (HER2/copy number of centromere of chromosome 17 \[CEP17\] ratio \< 2.0 or \< 4 Her-2/neu signals per nucleus)
•Any number of prior therapies for metastatic breast cancer is allowed; patients with weakly estrogen receptor positive breast cancer who received any number of endocrine agents for metastatic breast cancer will also be eligible
•Prior taxane is allowed (as long as the patient is not experiencing grade \> 1 neuropathy and had no history of disease progression on a taxane therapy within 3 months prior to study enrollment)
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
•Life expectancy of greater than 12 weeks
•Leukocytes \>= 2,000/uL
•Absolute neutrophil count \>= 1,500/uL
+9 more criteria

Exclusion Criteria

•Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
•Patients who are receiving any other investigational agents within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose of the study regimen
•Prior radiation therapy within 2 weeks prior to the first dose of the study regimen
•Patients in whom prior treatment related toxicities have not recovered to grade 1 or less (except for alopecia)
•Recent initiation of bone modifying therapy with a bisphosphonate or denosumab unless it has been started more than 4 weeks prior to the first dose of the study regimen; patients who are already enrolled in this study can initiate bone modifying therapy after the first set of re-staging scans (\>= 8 weeks from cycle 1, day 1)
•Prior therapy with AT13387 or another HSP90 inhibitor
•Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; however, patients with previously treated and stable brain metastases are eligible as long as they are no longer requiring steroids, completed radiation therapy more than 2 weeks prior to the first dose of study regimen and have no seizures or worsening neurologic symptoms
•History of grade 3-4 immediate hypersensitivity reaction to paclitaxel
•History of clinically significant allergic reactions attributed to compounds of similar chemical or biologic composition to AT13387 or paclitaxel
•Based on investigator's brochure, AT13387 has no significant effects on inhibition or activation of cytochrome P450 (CYP), including 1A2, 3A4, 2D6, 2C9, and 2C19 at the half maximal inhibitory concentration (IC50) \> 10 uM. Preclinical studies indicated that AT13387 is only a modest inhibitor of P-glycoprotein (P-gp). Paclitaxel is a substrate of CYP2C8 and CYP3A4. The use of CYP2C8 and CYP3A4 inhibitors/inducers while not prohibited in this study, is discouraged whenever feasible; concurrent use of strong CYP2C8 and CYP3A4 inhibitors/inducers should be documented and the principal investigator (PI) of the study shall be notified prior to dosing; as part of the enrollment/informed consent procedures, the patients will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
+5 more criteria

Locations (4)

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Key Dates

Start Date

January 15, 2016

Primary Completion Date

October 26, 2022

Completion Date

October 26, 2022

Last Updated

November 4, 2022

Enrollment

ACTUAL participants

Conditions

Advanced Breast CarcinomaMetastatic Breast CarcinomaStage III Breast Cancer AJCC v7Stage IIIA Breast Cancer AJCC v7Stage IIIB Breast Cancer AJCC v7Stage IIIC Breast Cancer AJCC v7Stage IV Breast Cancer AJCC v6 and v7Triple-Negative Breast Carcinoma

Interventions

Laboratory Biomarker Analysis

OTHER

Onalespib

DRUG

Paclitaxel

DRUG

Pharmacological Study

OTHER

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

NCT04704661

Advanced Breast CarcinomaAdvanced Colon Carcinoma+38 more

View study

RECRUITINGPHASE1

Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

NCT05372640

Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8+6 more

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: November 4, 2022Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Onalespib and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer

Inclusion Criteria

Exclusion Criteria

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations

A Study Comparing Cancer Imaging Approaches in People With Lobular Breast Cancer

An Optimized Ultrasound Twinkling Marker for the Imaging of Lymph Nodes in Patients With Clinically Node-Positive Breast Cancer, The UTMOST2 Trial

Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection