Ruxolitinib + Chemotherapy for Ovarian Cancer

Recruiting at 121 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: NRG Oncology

Must not be taking: Antibiotics, Antifungals, Antivirals, others

Disqualifiers: Other malignancies, Prior chemotherapy, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 6

147 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does exclude patients who are on concurrent anticancer therapy or have received an investigational study drug recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Ruxolitinib and chemotherapy for ovarian cancer?

Research shows that the combination of paclitaxel and carboplatin is effective for treating advanced ovarian cancer, with studies indicating it improves survival rates and is well-tolerated. While Ruxolitinib is not specifically mentioned, the effectiveness of paclitaxel and carboplatin provides a strong foundation for exploring additional benefits with Ruxolitinib. ^{1 2 3 4 5}

Is the combination of Ruxolitinib and chemotherapy safe for treating ovarian cancer?

The combination of paclitaxel and carboplatin, which are part of the chemotherapy regimen, has been shown to be generally safe for treating advanced ovarian cancer, with common side effects including myelosuppression (a decrease in bone marrow activity), neutropenia (low white blood cell count), and neuropathy (nerve damage). Ruxolitinib's safety in combination with these drugs specifically for ovarian cancer isn't detailed here, but it has been used safely in other conditions. ^{1 4 5 6 7}

What makes the drug combination of Ruxolitinib, Carboplatin, and Paclitaxel unique for ovarian cancer?

This treatment is unique because it combines Ruxolitinib, a drug that targets specific pathways involved in cancer cell growth, with Carboplatin and Paclitaxel, which are standard chemotherapy drugs. This combination aims to enhance the effectiveness of chemotherapy by potentially overcoming resistance in ovarian cancer cells. ^{1 8 9 10 11}

What is the purpose of this trial?

This phase I/II trial studies the side effects and the best dose of ruxolitinib phosphate when given together with paclitaxel and carboplatin and to see how well they work in treating patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with paclitaxel and carboplatin may be a better treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer compared to paclitaxel and carboplatin alone.

Research Team

Charles N Landen

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with advanced stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. Participants must have measurable disease, good performance status (able to carry out daily activities), and adequate blood counts. They should not have received prior treatment for their cancer and must be planning to undergo chemotherapy followed by surgery.

Inclusion Criteria

I have a tumor or lymph node that meets the size requirements for measurement.

Further protocol-specific assessments

I can care for myself and remain up and about more than 50% of my waking hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I (Cycles 1-3)

Patients receive ruxolitinib phosphate, paclitaxel, and carboplatin. Treatment repeats every 21 days for 3 cycles.

9 weeks

3 visits (in-person)

Surgery

Patients undergo tumor reductive surgery within 6 weeks after completion of cycle 3.

6 weeks

Treatment Phase I (Cycles 4-6)

Patients receive ruxolitinib phosphate, paclitaxel, and carboplatin. Treatment repeats every 21 days for 3 cycles.

9 weeks

3 visits (in-person)

Maintenance Therapy

Patients receive ruxolitinib phosphate. Treatment continues in the absence of disease progression or unacceptable toxicity.

3 months

Follow-up

Patients are monitored for safety and effectiveness after treatment. Follow-up every 3 months for 2 years, then every 6 months for 3 years.

5 years

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Ruxolitinib Phosphate

Trial Overview The study is testing the effectiveness of adding ruxolitinib phosphate to the standard chemotherapy drugs paclitaxel and carboplatin in treating these cancers. It's a phase I/II trial aiming to determine the best dose of ruxolitinib phosphate and how well it works with these chemotherapies.

Participant Groups

Group I: Arm II (ruxolitinib, paclitaxel, and carboplatin) Experimental Treatment 4 Interventions

See Detailed Description.

Group II: Arm I (paclitaxel and carboplatin) Active Control 3 Interventions

See Detailed Description.

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?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

In a study involving 637 patients with advanced ovarian cancer, the dose-dense regimen of paclitaxel and carboplatin significantly improved median progression-free survival to 28.2 months compared to 17.5 months with the conventional regimen.

The dose-dense treatment also resulted in a longer median overall survival of 100.5 months versus 62.2 months for the conventional treatment, suggesting it could become a new standard of care for first-line chemotherapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Katsumata, N., Yasuda, M., Isonishi, S., et al.[2022]

In a phase II trial involving 53 women with stage IV ovarian cancer, a novel treatment strategy combining modified chemotherapy and maintenance therapy with paclitaxel resulted in a 2-year overall survival rate of 48%, which is lower than the 60% survival rate of a historical control group treated with standard therapy.

The study highlighted the feasibility of adjusting treatment based on patient response, but ultimately concluded that this specific approach does not warrant further investigation due to its survival outcomes not being superior to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of single agent carboplatin followed by dose-intense paclitaxel, followed by maintenance paclitaxel therapy in stage IV ovarian, fallopian tube, and peritoneal cancers: a Southwest Oncology Group trial. Markman, M., Glass, T., Smith, HO., et al.[2019]

Paclitaxel has recently become a standard chemotherapy treatment for advanced ovarian cancer, especially when combined with platinum compounds, based on a large randomized trial by the Gynaecologic Oncology Group.

Ongoing clinical trials are investigating the optimal use of paclitaxel, including its dosage, administration schedule, and comparing the effectiveness and side effects of different platinum combinations (carboplatin vs. cisplatin).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. Ozols, RF.[2019]

In a multicenter phase II study involving 50 patients with advanced ovarian cancer who had previously undergone platinum-based chemotherapy, the combination of paclitaxel and carboplatin showed an overall response rate of 43%, indicating its efficacy in this patient population.

The treatment was generally safe, with myelosuppression being the most common severe side effect, but only one case of neutropenic fever was reported, suggesting that this regimen can be administered safely to outpatients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study. Pujade-Lauraine, E., Guastalla, JP., Weber, B., et al.[2015]

Docetaxel combined with carboplatin is a feasible and tolerable first-line treatment option for newly diagnosed epithelial ovarian cancer, showing no significant difference in progression-free or overall survival compared to the traditional paclitaxel and carboplatin combination in a study of 1,077 patients.

While docetaxel was associated with more myelosuppression, it resulted in fewer cases of neuropathy compared to paclitaxel, leading to better quality-of-life outcomes for patients receiving docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. Vasey, PA.[2018]

The combination of monthly carboplatin and weekly paclitaxel showed an impressive overall response rate of 85% in 20 patients with recurrent ovarian cancer, indicating its efficacy for both platinum-sensitive and platinum-resistant cases.

The treatment was generally well tolerated, with neutropenia being the only significant toxicity observed in 35% of patients, and hypersensitivity reactions were manageable with a desensitization protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of monthly carboplatin and weekly paclitaxel is highly active for the treatment of recurrent ovarian cancer. Hoekstra, AV., Hurteau, JA., Kirschner, CV., et al.[2015]

In a phase 1b/2 clinical trial involving 118 patients with recurrent platinum-sensitive epithelial ovarian cancer, the combination of ralimetinib with gemcitabine and carboplatin showed a statistically significant improvement in progression-free survival (PFS), with a median of 10.3 months compared to 7.9 months for the placebo group.

The safety profile of the ralimetinib combination therapy was generally consistent with standard chemotherapy, although there was a higher incidence of grade 3/4 elevated alanine aminotransferase in the ralimetinib group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled phase 1b/2 study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine and carboplatin versus gemcitabine and carboplatin for women with recurrent platinum-sensitive ovarian cancer. Vergote, I., Heitz, F., Buderath, P., et al.[2022]

References

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

Treatment of ovarian cancer: current status. [2015]

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

Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. [2022]

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

Phase II trial of single agent carboplatin followed by dose-intense paclitaxel, followed by maintenance paclitaxel therapy in stage IV ovarian, fallopian tube, and peritoneal cancers: a Southwest Oncology Group trial. [2019]

4. England pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. [2019]

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

Paclitaxel (Taxol)/carboplatin combination chemotherapy in the treatment of advanced ovarian cancer. [2015]

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

Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study. [2015]

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

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. [2018]

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

The combination of monthly carboplatin and weekly paclitaxel is highly active for the treatment of recurrent ovarian cancer. [2015]

9. England pubmed.ncbi.nlm.nih.gov

The role of apatinib combined with paclitaxel (aluminum binding type) in platinum-resistant ovarian cancer. [2023]

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

A randomized, double-blind, placebo-controlled phase 1b/2 study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine and carboplatin versus gemcitabine and carboplatin for women with recurrent platinum-sensitive ovarian cancer. [2022]

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

A phase II study of a paclitaxel and oxaliplatin combination in platinum-sensitive recurrent advanced ovarian cancer patients. [2020]