Abraxane + Mifepristone for Advanced Breast Cancer

Not currently recruiting at 4 trial locations

Overseen By Bernadette Libao

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: CYP3A4 inducers, NSAIDs

Disqualifiers: Active second malignancy, Uncontrolled illness, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced breast cancer, specifically targeting triple-negative breast cancer that tests positive for glucocorticoid receptors. The study will assess whether adding mifepristone (also known as Mifeprex or Korlym) to nab-paclitaxel (marketed as Abraxane) offers better disease control compared to nab-paclitaxel with a placebo (a non-active substance resembling the drug). Ideal participants are those with advanced triple-negative breast cancer who have not previously received nab-paclitaxel or mifepristone. The trial aims to determine if the combination treatment can slow cancer growth and improve outcomes. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that certain medications may interact with mifepristone. Specifically, drugs that affect CYP3A4 and CYP2C9/CYP2C8 enzymes might need to be adjusted. It's best to discuss your current medications with the trial team.

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

Research has shown that nab-paclitaxel (Abraxane) is usually well-tolerated, even in advanced breast cancer cases. Studies have found that patients might experience some side effects, but these are generally manageable. Common side effects include low blood cell counts, hair loss, and tiredness.

Researchers are testing mifepristone with nab-paclitaxel to determine if it enhances treatment effectiveness. The goal is to find the safest dose of mifepristone when used with nab-paclitaxel. Other studies have reported side effects like nausea and tiredness with mifepristone, but these are often mild.

In summary, both nab-paclitaxel and mifepristone have demonstrated a reasonable safety profile in past research, with side effects being mostly manageable. This combination is still under study to ensure optimal dosing and safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the combination of Nab-Paclitaxel and Mifepristone for advanced breast cancer because it targets the cancer differently from traditional treatments. Most breast cancer therapies focus on stopping cell division or damaging DNA in cancer cells, but Mifepristone blocks progesterone, a hormone that can promote breast cancer growth. This combination aims to enhance the effectiveness of Nab-Paclitaxel, a chemotherapy drug, by making cancer cells more susceptible to treatment. Unlike the standard of care, which typically involves chemotherapy alone, this dual approach could offer a more targeted attack on cancer cells, potentially improving outcomes for patients with advanced stages of breast cancer.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

This trial will compare two treatment arms for advanced triple-negative breast cancer (TNBC): one with nab-paclitaxel and mifepristone, and another with nab-paclitaxel and a placebo. Research has shown mixed results for the combination of nab-paclitaxel and mifepristone. Nab-paclitaxel alone has an average survival time of 6 months. Adding mifepristone increases this average survival time to 9 months. However, the period during which the cancer does not worsen remains about 3 months for both treatments. The percentage of patients whose cancer shrinks or disappears is slightly lower with the combination treatment at 23%, compared to 31.5% with nab-paclitaxel alone. These findings suggest that adding mifepristone may help patients live longer, but it does not appear to prevent cancer progression or increase the number of patients who experience tumor reduction or disappearance. ^{1 2 3 4 6}

Who Is on the Research Team?

Rita Nanda, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with advanced triple-negative breast cancer that's glucocorticoid receptor-positive. They can have had some prior treatments but must be in good enough health to participate, not pregnant or breastfeeding, and willing to use contraception. People with active infections, heart issues, certain mental health conditions, or those who've recently had other treatments are excluded.

Inclusion Criteria

I am committed to not having sex or using birth control if I can have children.

Ability to understand and the willingness to sign a written informed consent document

I am a man who will not have sex or will use a condom with women who can get pregnant.

Exclusion Criteria

I have brain metastases, haven't finished brain radiation, and stopped steroids over a week ago.

I am allergic to medications similar to mifepristone or paclitaxel.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nab-paclitaxel with or without mifepristone in 28-day cycles

12 months

Visits on days 1, 8, and 15 of each 28-day cycle

Pharmacokinetic Study

Pharmacokinetic studies are performed in the first 20 patients at pre-specified PK sites

During treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Mifepristone
• Nab-Paclitaxel
• Placebo

Trial Overview The study tests if adding Mifepristone to the chemotherapy drug Nab-Paclitaxel improves outcomes for patients with a specific type of breast cancer. Participants will either receive Mifepristone or a placebo alongside Nab-Paclitaxel and will be monitored over a year after treatment completion.

How Is the Trial Designed?

Group I: Nab-Paclitaxel+Mifepristone Experimental Treatment 2 Interventions

Patients will receive mifepristone 300 mg daily on the day prior to and day of each dose of nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle)

Group II: Nab-Paclitaxel+Placebo Placebo Group 2 Interventions

Patients will receive placebo and nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle)

Nab-Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer

Approved in European Union as Abraxane for:

• Breast cancer
• Pancreatic cancer

Approved in Canada as Abraxane for:

• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study involving 74 patients with metastatic melanoma, nab-Paclitaxel showed a response rate of 21.6% in chemotherapy-naive patients and 2.7% in previously treated patients, indicating better efficacy in those who had not undergone prior treatment.

The treatment was well tolerated, with 78% of previously treated patients and 49% of chemotherapy-naive patients able to complete therapy without dose reductions, suggesting a favorable safety profile compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Hersh, EM., O'Day, SJ., Ribas, A., et al.[2020]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

Nab-paclitaxel (Abraxane) is an effective treatment for metastatic breast cancer, showing a superior therapeutic index compared to conventional paclitaxel in a Phase III study with a standard dose of 260 mg/m² every three weeks.

In patients with poor prognostic factors, nab-paclitaxel demonstrated rapid and significant tumor responses, indicating it may be particularly beneficial for those with more severe disease, and lower doses (100 and 150 mg/m² weekly) also showed promising efficacy, suggesting potential for dose tailoring in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive metastatic breast cancer. Ciruelos, E., Jackisch, C.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39928262/

A randomized phase II trial of nab-paclitaxel with or without ... We hypothesized that pretreatment with mifepristone, a potent GR antagonist, would enhance nab-paclitaxel efficacy in advanced TNBC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01493310

Nab-paclitaxel (Abraxane) With or Without Mifepristone in ... This trial will find the best dose of mifepristone when given together with nab-paclitaxel (Abraxane) based on the side effects of the two drugs in patients ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11952973/

A randomized phase II trial of nab-paclitaxel with or without ... The addition of mifepristone to nab-paclitaxel did not improve PFS (3.0 m vs 3.0 m, p = 0.687) or overall response rate (23% vs 31.5%) compared to nab- ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e13103

A randomized phase II trial of nab-paclitaxel with or without ... Median OS with nab-pac alone was 6.0 mos and in the combination arm was 9.0 mos (HR=0.67, 95% CI 0.29 – 1.16, p=0.350]. The pt on the mif arm ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01493310?cond=%22Breast%20Disease%22&intr=%22albumin-bound%20paclitaxel%22&viewType=Table&rank=4

Nab-paclitaxel (Abraxane) With or Without Mifepristone in ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

6. clin.larvol.com clin.larvol.com/trial-detail/NCT01493310

Nab-paclitaxel (Abraxane) With or Without Mifepristone in ... This study will seek the safest dose of mifepristone given in combination with nab-paclitaxel. Safety of each dose will be determined by the number and ...