Ruxolitinib + Chemotherapy for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of Ruxolitinib with chemotherapy to determine its effectiveness in treating Inflammatory Breast Cancer (IBC). Participants will receive Ruxolitinib, a JAK inhibitor, along with chemotherapy drugs such as Paclitaxel, Doxorubicin, and Cyclophosphamide to assess the efficacy of this combination. The trial is open to adults diagnosed with inflammatory breast cancer, including those with certain types that haven't spread extensively beyond the breast. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

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.

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

Research has shown that patients, including those with inflammatory breast cancer, usually tolerate ruxolitinib well. In past studies, most side effects were mild, with only a few serious issues reported. Paclitaxel, a common breast cancer treatment, has known side effects such as low blood cell counts, hair loss, and nerve pain. Serious reactions can occur but are less common. Understanding the safety of these drugs when used together is important. Overall, the combination appears manageable, but side effects can vary among individuals. Always discuss any concerns with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the addition of Ruxolitinib to existing chemotherapy regimens for breast cancer, which could offer a new way to enhance treatment effectiveness. Unlike standard treatments that typically focus on killing cancer cells directly, Ruxolitinib works by inhibiting certain proteins involved in cancer cell growth and survival, potentially making cancer cells more sensitive to chemotherapy. This combination approach aims to improve outcomes by using Paclitaxel alongside Ruxolitinib, followed by the standard Doxorubicin and Cyclophosphamide regimen, potentially offering an enhanced preoperative therapy option for patients. The hope is that this novel combination could lead to better cancer control and improved patient outcomes compared to traditional methods.

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

In this trial, some participants will receive a combination of ruxolitinib with paclitaxel. Studies have shown that this combination can help shrink tumors in inflammatory breast cancer (IBC) by enhancing the effectiveness of paclitaxel, a common chemotherapy drug. Early research suggests that ruxolitinib targets key pathways that aid tumor growth, making it a promising addition to treatment. Other participants will receive paclitaxel alone, which research indicates is already effective for treating advanced breast cancer, offering good response rates and manageable side effects. Overall, the trial aims to determine if combining ruxolitinib and paclitaxel could lead to better outcomes for patients with IBC. ^{6 7 8 9 10}

Who Is on the Research Team?

Filipa Lynce, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9016319/

A Real-World Efficacy of Nab-Paclitaxel Monotherapy in ... In conclusion, this real-world data shows that nab-paclitaxel is an effective treatment option in metastatic breast cancer. Nab-paclitaxel was well tolerated ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.00877

Nab-Paclitaxel: A New Standard of Care in Neoadjuvant ... Outcome Data for Trials of Nab-Paclitaxel in Metastatic Breast Cancer. A subsequent phase II trial in 302 patients with metastatic disease ...

3. nature.com nature.com/articles/s41598-019-57380-0

Efficacy and safety of nanoparticle-albumin-bound ... Nab-paclitaxel is an effective anti-tumor drug in the first-line treatment of MBC. Using nab-paclitaxel instead of sb-taxanes could ...

4. clinical-breast-cancer.com clinical-breast-cancer.com/article/S1526-8209(18)30064-8/fulltext

Final Effectiveness and Safety Results of NABUCCO A total of 697 patients had evaluable data with a median follow-up of 17.7 months. Median time to progression was 5.9 months (95% confidence ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-021-08441-z

A systematic review and meta-analysis of nab-paclitaxel ... Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3091407/

Safety and Efficacy of nab-Paclitaxel in the Treatment of ... The solvents used for dissolving hydrophobic molecules, paclitaxel and docetaxel are known to be associated with significant risk of hypersensitivity reactions ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/021660s047lbl.pdf

ABRAXANE (paclitaxel) Label - accessdata.fda.gov In clinical studies,. Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC), 47% of patients with non-small cell lung cancer ( ...

8. abraxanepro.com abraxanepro.com/important-safety-information

ABRAXANE® Safety Information The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, ...

9. facingourrisk.org facingourrisk.org/XRAY/FDA-warns-against-tecentriq-and-paclitaxel-combo-therapy

FDA issues alert on a drug combination to treat triple ... Patients with advanced triple-negative breast cancer (TNBC) should avoid taking the therapy drug Tecentriq with paclitaxel.

10. cancernetwork.com cancernetwork.com/view/fda-approves-abraxane-metastatic-breast-cancer

FDA Approves Abraxane for Metastatic Breast Cancer Safety data was obtained from 229 Abraxane and 225 Taxol patients participating in the pivotal study. Neutropenia was the most important and most common ...