CLINICAL TRIAL

Onalespib for Triple Negative Breast Neoplasms

Locally Advanced
Metastatic
Waitlist Available · 18+ · All Sexes · Pittsburgh, PA

This study is evaluating whether a drug called onalespib can be safely given with paclitaxel to treat breast cancer.

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About the trial for Triple Negative Breast Neoplasms

Eligible Conditions
Breast Neoplasms · Stage IIIC Breast Cancer AJCC v7 · Stage III Breast Cancer AJCC v7 · Stage IIIB Breast Cancer AJCC v7 · Metastatic Breast Carcinoma · Triple Negative Breast Carcinoma · Stage IIIA Breast Cancer AJCC v7 · Stage IV Breast Cancer AJCC v6 and v7 · Advanced Breast Carcinoma · Carcinoma · Triple Negative Breast Neoplasms

Treatment Groups

This trial involves 2 different treatments. Onalespib is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 1 and are in the first stage of evaluation with people.

Main TreatmentA portion of participants receive this new treatment to see if it outperforms the control.
Pharmacological Study
OTHER
Onalespib
DRUG
Paclitaxel
DRUG
Laboratory Biomarker Analysis
OTHER
Control TreatmentAnother portion of participants receive the standard treatment to act as a baseline.

About The Treatment

Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Paclitaxel
FDA approved

Eligibility

This trial is for patients born any sex aged 18 and older. There are 10 eligibility criteria to participate in this trial as listed below.

Inclusion & Exclusion Checklist
Mark “yes” if the following statements are true for you:
Patients with a primary or metastatic breast tumor that is negative for over-expression of estrogen and progesterone receptors will be eligible show original
The primary and/or metastatic breast tumor must be negative for human epidermal growth factor receptor over-expression (based on immunohistochemistry [IHC] or FISH) show original
Patients who have previously received any number of therapies for metastatic breast cancer are eligible for the study, as are those with weakly estrogen receptor positive breast cancer who have received any number of endocrine agents for metastatic breast cancer. show original
Individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 (Karnofsky performance status of 60% or greater) are eligible for this study. show original
A person has an absolute neutrophil count of at least 1,500/uL if their white blood cells contain at least 1,500 neutrophils. show original
The life expectancy of a person with this condition is greater than 12 weeks. show original
Patients must have advanced or metastatic breast cancer for which there is no known cure show original
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
As long as the patient has no history of disease progression on a taxane therapy within 3 months prior to study enrollment, and they are not experiencing grade > 1 neuropathy, they are allowed to receive prior taxane therapy. show original
Leukocytes >= 2,000/uL
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Odds of Eligibility
Unknown<50%
Be sure to apply to 2-3 other trials, as you have a low likelihood of qualifying for this one.Apply To This Trial
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Approximate Timelines

Please note that timelines for treatment and screening will vary by patient
Screening: ~3 weeks
Treatment: varies
Reporting: From study enrollment to first documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause (whichever occurs first), assessed up to 2 years
Screening: ~3 weeks
Treatment: Varies
Reporting: From study enrollment to first documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause (whichever occurs first), assessed up to 2 years
This trial has approximate timelines as follows: 3 weeks for initial screening, variable treatment timelines, and reporting: From study enrollment to first documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause (whichever occurs first), assessed up to 2 years.
View detailed reporting requirements
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- What options you have available- The pros & cons of this trial
- Whether you're likely to qualify- What the enrollment process looks like

Measurement Requirements

This trial is evaluating whether Onalespib will improve 2 primary outcomes and 5 secondary outcomes in patients with Triple Negative Breast Neoplasms. Measurement will happen over the course of Up to 28 days.

Recommended phase 2 dose (R2PD)
UP TO 28 DAYS
Defined as level at which no more than 1 of 6 patients experience a dose limiting toxicity (maximum tolerated dose or [MTD]); or doses of the combination below MTD, if in the opinion of the investigators, lower doses are better tolerated and safer.
UP TO 28 DAYS
Pharmacokinetic (PK) parameters of paclitaxel
PRE-DOSE, IMMEDIATELY PRIOR TO END OF INFUSION, 0.5, 1, 2, 4, 6, 8, AND 24 HOURS AFTER END OF INFUSION ON DAYS 1 AND 8 OF COURSE 1 (AND IMMEDIATELY PRIOR TO END OF INFUSION OF ONALESPIB, PRIOR TO STARTING PACLITAXEL ON DAY 8)
A descriptive analysis will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
PRE-DOSE, IMMEDIATELY PRIOR TO END OF INFUSION, 0.5, 1, 2, 4, 6, 8, AND 24 HOURS AFTER END OF INFUSION ON DAYS 1 AND 8 OF COURSE 1 (AND IMMEDIATELY PRIOR TO END OF INFUSION OF ONALESPIB, PRIOR TO STARTING PACLITAXEL ON DAY 8)
Pharmacokinetic (PK) parameters of onalespib
PRE-DOSE, IMMEDIATELY PRIOR TO END OF INFUSION, 0.5, 1, 2, 4, 6, 8, AND 24 HOURS AFTER END OF INFUSION ON DAY -7 OF COURSE 1 AND DAY 8 (AND PRIOR TO STARTING PACLITAXEL, AND IMMEDIATELY PRIOR TO END OF INFUSION OF PACLITAXEL ON DAY 8)
A descriptive analysis will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
PRE-DOSE, IMMEDIATELY PRIOR TO END OF INFUSION, 0.5, 1, 2, 4, 6, 8, AND 24 HOURS AFTER END OF INFUSION ON DAY -7 OF COURSE 1 AND DAY 8 (AND PRIOR TO STARTING PACLITAXEL, AND IMMEDIATELY PRIOR TO END OF INFUSION OF PACLITAXEL ON DAY 8)
Overall response rate (partial response [PR]+ complete response [CR])
UP TO 6 MONTHS
Will be assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Overall response will be assessed in all patients in an exploratory manner, using summary statistics, by dose level. Will also calculate corresponding 95% binomial confidence intervals for these response rates.
UP TO 6 MONTHS
Response duration
FROM THE TIME MEASUREMENT CRITERIA ARE MET FOR COMPLETE RESPONSE (CR) OR PARTIAL RESPONSE (PR) (WHICHEVER IS FIRST RECORDED) UNTIL THE FIRST DATE THAT RECURRENT OR PROGRESSIVE DISEASE IS OBJECTIVELY DOCUMENTED, ASSESSED UP TO 2 YEARS
Will be based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
FROM THE TIME MEASUREMENT CRITERIA ARE MET FOR COMPLETE RESPONSE (CR) OR PARTIAL RESPONSE (PR) (WHICHEVER IS FIRST RECORDED) UNTIL THE FIRST DATE THAT RECURRENT OR PROGRESSIVE DISEASE IS OBJECTIVELY DOCUMENTED, ASSESSED UP TO 2 YEARS
Toxicity profile of onalespib in combination with paclitaxel
UP TO 2 YEARS
Will be based on the Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0.
UP TO 2 YEARS
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Patient Q & A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What are common treatments for triple negative breast neoplasms?

Several treatment options exist for triple negative breast neoplasms, including cytotoxic chemotherapy, hormone therapy, and chemotherapy with trastuzumab. Treating the cancer early through the use of cytotoxic or hormone therapy can help patients prevent symptoms and improve survival. Patients should consider enrolling in clinical trials to explore new treatments like trastuzumab (Herceptin).

Anonymous Patient Answer

What are the signs of triple negative breast neoplasms?

TNBCs usually appear as solid masses with a palpable and movable axillary nodule. Axillary enlargement and/or the presence of lymphovascular invasion or peritumoral lymphoplasmatic stroma might be present. Imaging studies are helpful to the radiologists to provide an overall picture which facilitates the diagnosis. Radiologists need to be aware of such lesions since they respond well to hormonal therapy.

Anonymous Patient Answer

Can triple negative breast neoplasms be cured?

The lack of evidence of curative treatment for triple negative breast cancers in this population means that patients with TNBC are never going to be cured of their condition. Therefore, it is important that TNBC patients receive the best evidence based treatment for their tumours.

Anonymous Patient Answer

How many people get triple negative breast neoplasms a year in the United States?

Every 3 years, around 469,100 new cases of TNBC occur in Americans. The increased prevalence of triple negative breast cancer in African-American women is not restricted to high-risk subgroups as previously acknowledged.

Anonymous Patient Answer

What is triple negative breast neoplasms?

TNBCs are rare and most patients may not be diagnosed to this rare sub-type. The combination of morphological and molecular subtypes is important to improve management and patient outcomes. These patients should be treated according to NACTG recommendations for their disease, in order to achieve higher likelihood for a cure and better overall outcomes. The NACTG would be the best recommendation to evaluate and recommend in patients with TNBC and who is <30 years of age. Clinicians with more experience in treating TNBC and breast cancer patients should be consulted in selecting appropriate patients to participate in clinical trials. Finally, all the available drugs have been proven effective in TNBC patients and tailored for personalized treatment in future.

Anonymous Patient Answer

What causes triple negative breast neoplasms?

TNBC do not have a single and well-defined cause. Results from a recent paper suggest that tumors of TNBC should be considered as a distinct class of cancer, rather than simply TNBC variants of other breast cancer types.

Anonymous Patient Answer

What are the common side effects of onalespib?

Only 1 of the 42 patients on study had a significant clinical response. Most common was reversible stomatitis in 19 cases (42%). Dysgeusia (the unpleasant taste in the mouth) was reported by 34 patients (80%), predominantly in the first 3 on trial days. Other less common (>10% incidence) but serious clinical adverse events included fatigue (11 patients; 26%) and myelosuppression (4 patients; 10%).

Anonymous Patient Answer

What does onalespib usually treat?

As the efficacy of onalespib in triple-negative breast cancer has been proved, the use of this agent in this clinical setting needs to be further expanded. This retrospective study suggests that the presence of the ALK or mam-A or NTRK2 amplifications is of importance for selecting patients who may benefit from onalespib therapy. A more precise selection of patients for targeted therapies can be achieved by detecting these molecular alterations prior to treatment.

Anonymous Patient Answer

Who should consider clinical trials for triple negative breast neoplasms?

There is increasing interest in the treatment of triple negative breast neoplasms, and current trials show that patients with triple negative breast neoplasms can benefit from targeted therapy.

Anonymous Patient Answer

Has onalespib proven to be more effective than a placebo?

As of the end of 2017, the RECIST v2.0 guideline has been updated, no longer requiring that the following be reported as interim findings: a 30% difference and a p-value, or better, at one year, or at three years; or 10% difference in p-value at two years, or better, without a p-value. Onalespib demonstrates higher rates of complete and overall response and more complete response rates at three and five years than a placebo in postmenopausal patients with platinum-resistant metastatic triple-negative breast cancer who have received two prior lines of chemotherapy.

Anonymous Patient Answer

Is onalespib safe for people?

Onalespib achieves a greater objective activity than placebo, without increasing rates of severe adverse events when compared to placebo, and is a promising drug for further investigation.

Anonymous Patient Answer

What is onalespib?

Although it is effective, the clinical use of afatinib or NS398 is associated with higher rates of sensory and motor deficits compared with erlotinib and/or docetaxel. In an effort to improve the tolerability of current tyrosine kinase inhibitor therapies, efforts to improve molecular and cellular mechanisms of cancer progression, and reduce EGFR-driven drug resistance as a result of increased targeting of additional pathways has become an active focus of current research. Ataluren has been proposed as a potential adjuvant therapy for triple-negative breast cancer with an unfavorable prognosis due to the lack of EGFR and ER signaling blockade, as well as AKT/GSK-3β and MAPK/ERK pathways inhibition.

Anonymous Patient Answer
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