Abraxane + Mifepristone for Advanced Breast Cancer

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

29 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Abraxane + Mifepristone for advanced breast cancer?

Research shows that Abraxane, a form of paclitaxel, is effective in treating metastatic breast cancer, with better response rates and longer survival compared to conventional paclitaxel. It is also well-tolerated, making it a promising option for patients with advanced breast cancer. ^{1 2 3 4 5}

Is the combination of Abraxane and Mifepristone safe for humans?

Abraxane (nab-paclitaxel) is generally considered safe for use in humans, as it is FDA approved for several cancers, including metastatic breast cancer, and has been evaluated for safety in various studies. However, specific safety data for the combination of Abraxane and Mifepristone is not provided in the available research. ^{1 2 4 5 6}

What makes the drug Abraxane unique for treating advanced breast cancer?

Abraxane is unique because it is an albumin-bound form of paclitaxel that doesn't require a toxic solvent, making it safer and potentially more effective by increasing the drug concentration in tumors. This formulation allows for better delivery to the tumor and has shown superior response rates and longer survival compared to conventional paclitaxel in metastatic breast cancer. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a randomized, placebo-controlled, double-blind, phase II trial of nab-paclitaxel with or without mifepristone for advanced, glucocorticoid receptor-positive, triple-negative breast cancer. A total of 64 patients will receive nab-paclitaxel. Patients will be randomly assigned to either receive placebo or to receive mifepristone daily on the day prior to and day of each dose of nab-paclitaxel. Patients will be enrolled over 12 months and followed for 12 months following completion of study. To expand and follow up on the investigators understanding of a potential pharmacokinetic (PK) interaction between nab-paclitaxel and mifepristone, investigators will perform PK studies in the first 20 patients enrolled at pre-specified "PK sites".

Research Team

Rita Nanda, MD

Principal Investigator

University of Chicago

Eligibility Criteria

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.

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

I have mild or no nerve damage in my hands and feet.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. United States 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). [2022]

3. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

5. England 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. [2020]