Ruxolitinib + Chemotherapy for Breast Cancer

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors, Fluconazole

Disqualifiers: Brain metastases, Uncontrolled illness, Pregnancy, 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: 1

Duration: 12 weeks

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Ruxolitinib combined with three other cancer drugs to treat Inflammatory Breast Cancer (IBC). It targets patients who may not respond well to typical treatments. Ruxolitinib works by blocking a pathway that cancer cells need to grow and helps other drugs be more effective. Ruxolitinib has been beneficial in the treatment of myelofibrosis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take medications that strongly inhibit CYP3A4 (a liver enzyme) or fluconazole. There may be a washout period for these medications, so check with the trial team for details.

What evidence supports the effectiveness of the drug combination Ruxolitinib, Cyclophosphamide, Doxorubicin, and Paclitaxel for breast cancer?

Research shows that the combination of doxorubicin and paclitaxel is highly effective for treating advanced breast cancer, with remission rates ranging from 60% to 90%. Additionally, combining paclitaxel with cyclophosphamide has been effective in clinical development, suggesting that these components can work well together in treating breast cancer. ^{1 2 3 4 5}

Is the combination of Ruxolitinib and chemotherapy safe for humans?

The combination of doxorubicin and paclitaxel, which are part of the chemotherapy regimen, is known to cause heart-related side effects. However, adding dexrazoxane may help reduce these risks. Paclitaxel can also cause other side effects like allergic reactions and nerve damage. In older breast cancer patients, a similar combination with cyclophosphamide showed no heart-related symptoms in the first year of treatment. ^{1 4 6 7 8}

What makes the drug combination of Ruxolitinib and chemotherapy unique for breast cancer treatment?

The combination of Ruxolitinib with chemotherapy drugs like Cyclophosphamide, Doxorubicin, and Paclitaxel is unique because Ruxolitinib, a JAK inhibitor, may enhance the effectiveness of chemotherapy by targeting specific pathways involved in cancer cell growth, potentially offering a novel approach compared to traditional chemotherapy regimens alone. ^{1 4 9 10 11}

Research Team

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with triple-negative inflammatory breast cancer, who haven't had prior therapy for any breast cancer. They must be in good health with normal organ and marrow function, can have minimal metastatic disease, and agree to use contraception. Excluded are those on certain drugs or with brain metastases, HIV not on antiretrovirals, previous reactions to similar compounds as ruxolitinib, or uncontrolled illnesses.

Inclusion Criteria

You are in good enough physical condition to carry out your normal activities or to walk and carry out light work.

Both men and women are allowed.

Women of child-bearing potential and men must agree to use adequate contraception.

Exclusion Criteria

Participants may not be receiving any other investigational agents.

Participants with known brain metastases should be excluded from this clinical trial.

You have had allergic reactions to drugs similar to ruxolitinib.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-In Phase

Participants receive Ruxolitinib alone or with Paclitaxel for 7 days to assess biologic response

1 week

1 visit (in-person)

Treatment

Participants receive Paclitaxel with daily Ruxolitinib followed by Doxorubicin and Cyclophosphamide (AC) every 2 weeks for 4 cycles

12 weeks

Weekly visits for Paclitaxel, bi-weekly visits for AC

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

Regular follow-up visits

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin
• Paclitaxel
• Ruxolitinib

Trial Overview The study tests Ruxolitinib combined with chemotherapy drugs Paclitaxel (Taxol), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) as a treatment for Inflammatory Breast Cancer. It aims to see if this combination is effective before surgery in patients diagnosed with this aggressive form of breast cancer.

Participant Groups

Group I: Ruxolitinib with Paclitaxel (12weeks) Experimental Treatment 4 Interventions

Paclitaxel is administered with daily Ruxolitinib, followed by standard Doxorubicin and Cyclophosphamide (AC) given every 2 weeks for 4 cycles preoperatively * 16 patients will be randomized from the Run-In 7 days of Ruxolitinib * The drug will be administered at a pre-determine dosage

Group II: Ruxolitinib and Paclitaxel (12weeks) Experimental Treatment 4 Interventions

Paclitaxel is administered with daily Ruxolitinib, followed by standard Doxorubicin and Cyclophosphamide (AC) given every 2 weeks for 4 cycles preoperatively * 32 patients will be randomized from the Run-In 7 days of Ruxolitinib + Paclitaxel * The drug will be administered at a pre-determine dosage

Group III: Paclitaxel (12weeks) Experimental Treatment 4 Interventions

Paclitaxel is administered weekly followed by standard Doxorubicin and Dyclophosphamide (AC) given every 2 weeks for 4 cycles preoperatively * 16 patients will be randomized from the Run-In 7 days of Ruxolitinib * The drug will be administered at a pre-determine dosage

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

The combination of paclitaxel and doxorubicin has significantly improved clinical outcomes for breast cancer patients, particularly in neoadjuvant settings for locally advanced cases.

However, this combination therapy is associated with cardiac toxicity, highlighting the need for careful monitoring and future research to mitigate these risks while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of the management of cancer of the breast]. Ferrero, JM., Magné, N., Foa, C., et al.[2015]

The combination of Doxil (40 mg/m2) and vinorelbine (30 mg/m2) was found to be effective in treating metastatic breast cancer in a phase I study involving 30 women, with a recommended schedule for further testing.

This combination therapy demonstrated a favorable toxicity profile, with minimal severe side effects like neutropenia and a low incidence of significant nausea, vomiting, or hair loss, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. Burstein, HJ., Ramirez, MJ., Petros, WP., et al.[2020]

The combination of doxorubicin (Dox) and paclitaxel has been established as a superior treatment for metastatic breast cancer, showing better response rates and longer time to disease progression compared to either drug alone, based on a phase III study.

New agents like Herceptin (trastuzumab) and DPPE are being investigated to enhance the efficacy of Dox and paclitaxel, with early results indicating they may improve response rates and prolong disease progression time when used in combination with these chemotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in chemotherapy of advanced breast cancer. Lebwohl, DE., Canetta, R.[2016]

A new regimen combining doxorubicin and paclitaxel has been developed that is both well-tolerated and highly effective, utilizing bolus administration of doxorubicin and a 3-hour infusion of paclitaxel, overcoming previous schedule-dependent toxicity issues.

Paclitaxel has shown promising results when combined with fluorouracil and folinic acid in patients with extensive prior chemotherapy, and adding mitoxantrone to this combination appears to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-based combination chemotherapy for breast cancer. Hortobagyi, GN.[2015]

Combining paclitaxel with doxorubicin has shown impressive remission rates for metastatic breast cancer, with overall rates exceeding 90% and nearly 50% achieving complete remission, especially when administered in a specific sequence.

While other combinations of paclitaxel with drugs like cisplatin and vinorelbine have shown variable results, the doxorubicin/paclitaxel combination remains the most effective and tolerable treatment option currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. Hortobagyi, GN., Ibrahim, N.[2018]

In a study of 47 elderly women with high-risk breast cancer, the combination of Non-Pegylated Liposomal Doxorubicin (NPL-DOX) and Cyclophosphamide followed by weekly Paclitaxel showed a low rate of cardiac toxicity over a median follow-up of 76 months, with only one case of grade 3 congestive heart failure reported.

While there was a gradual decline in left ventricular ejection fraction (LVEF) over time, it remained above 50% and did not lead to any significant clinical symptoms, indicating that the treatment is relatively safe for cardiac health in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study. Coltelli, L., Finale, C., Musettini, G., et al.[2023]

In a study involving male rats treated with doxorubicin (DOX) and paclitaxel (PTX), the addition of dexrazoxane (DZR) significantly reduced the cardiotoxic effects of DOX, demonstrating its cardioprotective properties.

The combination of DOX and PTX did not worsen the heart damage caused by DOX alone, and DZR maintained its protective effects without increasing noncardiac toxicity, suggesting a safer treatment regimen for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. Della Torre, P., Imondi, AR., Bernardi, C., et al.[2015]

Paclitaxel (Taxol) is an effective chemotherapy agent for treating ovarian cancer and metastatic breast cancer, particularly in patients who have not responded to platinum-based treatments.

Nurses must be aware of the potential side effects of Paclitaxel, such as hypersensitivity reactions and peripheral neuropathy, and follow specific administration guidelines to avoid complications related to its interaction with PVC intravenous-giving sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. Preston, NJ.[2019]

References

1. France pubmed.ncbi.nlm.nih.gov

[Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of the management of cancer of the breast]. [2015]

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

Phase I study of Doxil and vinorelbine in metastatic breast cancer. [2020]

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

New developments in chemotherapy of advanced breast cancer. [2016]

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

Paclitaxel-based combination chemotherapy for breast cancer. [2015]

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

Paclitaxel-containing combination chemotherapy for metastatic breast cancer. [2018]

6. Italy pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. [2015]

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

Paclitaxel (Taxol)--a guide to administration. [2019]

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

Optimal dosing of paclitaxel and doxorubicin in metastatic breast cancer. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Paclitaxel and mitoxantrone in the treatment of metastatic breast cancer: a phase II trial of the Minnie Pearl Cancer Research Network. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (Lipo-Dox®) combined with cyclophosphamide and 5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated metastatic breast cancer: an open-label, multi-center, non-comparative phase II study. [2018]