Carboplatin + Nab-Paclitaxel +/- Vorinostat for Breast Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Antiretrovirals, Histone deacetylase inhibitors

Disqualifiers: Peripheral neuropathy, Hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help carboplatin and paclitaxel albumin-stabilized nanoparticle formulation work better by making tumor cells more sensitive to the drugs. Giving chemotherapy with or without vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This randomized phase II trial is studying how well giving carboplatin together with paclitaxel albumin-stabilized nanoparticle formulation works with or without vorinostat in treating women with breast cancer that can be removed by surgery.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as valproic acid or other histone deacetylase inhibitors, at least 4 weeks before starting. You also cannot be on any chemotherapy, radiotherapy, or endocrine therapy for this cancer, and no concurrent antiretroviral therapy if you are HIV-positive.

Is the combination of Carboplatin, Nab-Paclitaxel, and Vorinostat safe for humans?

The combination of Carboplatin and Nab-Paclitaxel has been shown to be well tolerated in elderly patients with lung cancer, with less nerve-related side effects. Additionally, a study on Paclitaxel and Vorinostat in breast cancer suggests that this combination in a specific nanoparticle form may have less toxicity compared to traditional formulations. ^{1 2 3 4 5}

What makes the drug Carboplatin + Nab-Paclitaxel +/- Vorinostat unique for breast cancer treatment?

This drug combination is unique because it includes nab-paclitaxel, a form of paclitaxel bound to albumin (a protein in the blood), which enhances drug delivery to tumors and reduces side effects compared to traditional formulations. Nab-paclitaxel is solvent-free, minimizing the risk of allergic reactions, and has shown improved effectiveness and tolerability in breast cancer treatment. ^{2 6 7 8 9}

What data supports the effectiveness of the drug combination Carboplatin + Nab-Paclitaxel +/- Vorinostat for breast cancer?

Research shows that nab-paclitaxel, a component of the drug combination, is effective and less toxic in treating breast cancer compared to traditional formulations. Additionally, the combination of paclitaxel and carboplatin has shown promising response rates and manageable toxicity in advanced breast cancer, suggesting potential effectiveness for this drug combination. ^{1 6 10 11 12}

Who Is on the Research Team?

Vered Stearns, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for women with newly diagnosed operable breast cancer. Participants should have specific types of breast cancer, meet certain blood and organ function criteria, agree to non-hormonal contraception, and not be pregnant or nursing. Those with severe complications risk, prior systemic treatment for this cancer, or other exclusions cannot join.

Inclusion Criteria

My breast cancer is of the infiltrating lobular type.

My cancer is not HER2 positive.

My breast cancer is both ductal and lobular.

Exclusion Criteria

I haven't had any cancer except for skin cancer in the last 5 years.

I am currently taking medication that affects cell DNA.

I am not taking any experimental drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.

12 weeks

Primary Study

Patients are randomized to receive either carboplatin and paclitaxel with placebo or with vorinostat. Treatment repeats weekly for 12 weeks.

12 weeks

Surgery

Within 2-4 weeks after completion of neoadjuvant chemotherapy, patients undergo breast conserving surgery or mastectomy.

2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment.

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel albumin-stabilized nanoparticle formulation
• Vorinostat

Trial Overview The study tests how well carboplatin and nab-paclitaxel chemotherapy work when given with or without vorinostat before surgery. The goal is to see if adding vorinostat makes the chemo more effective in shrinking tumors in preparation for surgical removal.

How Is the Trial Designed?

Group I: Arm II Experimental Treatment 3 Interventions

Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm I Active Control 3 Interventions

Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nab-paclitaxel, a nanoparticle albumin-bound form of paclitaxel, is the first nanotechnology-based drug approved for cancer treatment, showing significant promise in breast and pancreatic cancers.

This innovative drug not only enhances the effectiveness and reduces the toxicity of traditional treatments but also demonstrates activity in cancers that typically do not respond to standard taxane therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time? Cucinotto, I., Fiorillo, L., Gualtieri, S., et al.[2022]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a phase II clinical trial involving 55 patients with operable breast cancer, preoperative chemotherapy using nanoparticle albumin-bound paclitaxel (nab-PTX) followed by an epirubicin and cyclophosphamide regimen achieved a pathological complete response (pCR) rate of 22.2%, indicating its efficacy in treating this condition.

The study found that HER2-positive patients had a significantly higher pCR rate of 60%, suggesting that HER2 status is an important factor in predicting treatment response, while the overall safety profile of the treatment was considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. Futamura, M., Nagao, Y., Ishihara, K., et al.[2018]

The combination of paclitaxel and carboplatin (PC) has shown promising response rates of 40-60% and median survival times of 12-20 months in patients with advanced breast cancer, making it a viable alternative to traditional anthracycline-based treatments.

In a randomized phase III trial, PC demonstrated equivalent efficacy and manageable toxicity compared to the standard treatment of epirubicin/paclitaxel, suggesting it could be a safer option for patients with prior anthracycline exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy, and safety. Pentheroudakis, G., Razis, E., Athanassiadis, A., et al.[2018]

In a phase II trial involving 32 elderly patients with untreated advanced non-small cell lung cancer, the combination of weekly nanoparticle albumin-bound-paclitaxel and carboplatin showed a 50% overall response rate and a median overall survival of 17.5 months, indicating significant efficacy.

The treatment was well tolerated, with no treatment-related deaths or febrile neutropenia reported, and it resulted in less neuropathic toxicity compared to traditional regimens, making it a promising option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301. Miyauchi, E., Inoue, A., Usui, K., et al.[2018]

Nab-paclitaxel significantly improves overall response (OR) and partial response (PR) rates in advanced non-small cell lung cancer (NSCLC), especially in squamous cell carcinoma and as a second-line treatment, based on a meta-analysis of 35 studies involving various trial designs.

While nab-paclitaxel shows marginal improvements in overall survival (OS) and progression-free survival (PFS), the evidence regarding its safety profile and reduction of adverse events remains inconclusive, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies. Suwannasom, N., Sriaksorn, N., Thepmalee, C., et al.[2023]

Nab-paclitaxel, a formulation of paclitaxel bound to nanoparticles, shows reduced risk of hypersensitivity reactions and allows for potential dose escalation, making it a safer option for patients.

In Phase III studies, nab-paclitaxel demonstrated better efficacy and tolerability compared to conventional treatments like docetaxel and paclitaxel in patients with metastatic breast cancer, suggesting its potential for broader use in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[nab-Paclitaxel. Clinical value of an innovative taxane-containing formulation]. Lipp, HP.[2015]

In a study of women with metastatic breast cancer treated with nab-paclitaxel, 43% experienced a clinical benefit, with a median survival of 63.6 weeks, indicating its effectiveness as a treatment option.

Nab-paclitaxel was well tolerated, with no severe hypersensitivity reactions reported and mild sensory neuropathy being the most common side effect, suggesting a favorable safety profile compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer. Singh, RK., Pankaj, S., Kumar, S., et al.[2022]

Citations

1. Egypt pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time? [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy evaluation of albumin-bound paclitaxel combined with carboplatin as neoadjuvant chemotherapy for primary epithelial ovarian cancer. [2022]

3. Thailand pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial. [2018]

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

Paclitaxel-carboplatin combination chemotherapy in advanced breast cancer: accumulating evidence for synergy, efficacy, and safety. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

A phase II, multicenter, single-arm study of tri-weekly low-dose nanoparticle albumin-bound paclitaxel chemotherapy for patients with metastatic or recurrent breast cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies. [2023]

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

Exploring the synergistic behavior of paclitaxel and vorinostat upon co-loading in albumin nanoparticles for breast cancer management. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

[nab-Paclitaxel. Clinical value of an innovative taxane-containing formulation]. [2015]

11. Netherlands pubmed.ncbi.nlm.nih.gov

The efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel after cisplatin plus pemetrexed in non-squamous non-small-cell lung cancer patients. [2020]

12. Canada pubmed.ncbi.nlm.nih.gov

A Retrospective Study of Efficacy and Safety of Albumin-Bound Paclitaxel in Metastatic Breast Cancer. [2022]