Ruxolitinib + Chemotherapy for Ovarian Cancer

No longer recruiting at 123 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating advanced ovarian cancer by combining ruxolitinib phosphate, a JAK inhibitor, with standard chemotherapy drugs paclitaxel and carboplatin. Researchers aim to determine the optimal dose of ruxolitinib and assess whether its addition improves treatment outcomes. This trial targets patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer who plan to undergo chemotherapy followed by surgery. Participants should not have received prior treatments for these cancers. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

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

Research has shown that combining ruxolitinib with the chemotherapy drugs paclitaxel and carboplatin is generally well-tolerated. One study found that this combination improved outcomes for patients with advanced ovarian cancer without causing unexpected side effects. Another study assessed safety and found it acceptable for patients with late-stage ovarian cancer.

Paclitaxel and carboplatin are standard chemotherapy treatments with known side effects, such as nausea and low blood cell counts, which are usually manageable. Ruxolitinib, already approved by the FDA for other uses, has a proven safety record in humans.

Overall, existing research indicates that the combination is safe, particularly since ruxolitinib is already used in other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination treatment with Ruxolitinib for ovarian cancer because it introduces a new mechanism of action by targeting the JAK/STAT pathway, which is involved in cancer cell growth and survival. This is different from the standard chemotherapy options like Carboplatin and Paclitaxel that primarily work by damaging cancer cell DNA or inhibiting cell division. The addition of Ruxolitinib, an active ingredient not typically used in ovarian cancer treatment, offers a novel approach by potentially enhancing the effectiveness of chemotherapy and overcoming resistance. By integrating Ruxolitinib with traditional chemotherapy, there's hope for improved outcomes in tackling this challenging condition.

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

This trial will compare two treatment approaches for ovarian cancer. In one arm, participants will receive the usual chemotherapy drugs, paclitaxel and carboplatin. In the other arm, participants will receive a combination of ruxolitinib with paclitaxel and carboplatin. Research has shown that adding ruxolitinib to the usual chemotherapy might be more effective for treating ovarian cancer than using just paclitaxel and carboplatin. Studies have found that this combination helps patients live longer without their cancer worsening. Ruxolitinib blocks certain enzymes that help cancer cells grow, potentially enhancing the effects of chemotherapy. Results from previous patients suggest that this combination is generally well-tolerated and offers additional benefits to the standard treatment. These findings provide promising evidence for its potential effectiveness in managing advanced ovarian cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Charles N Landen

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.23.02076

Phase I and Randomized Phase II Study of Ruxolitinib With ... Ruxolitinib 15 mg PO twice a day was well tolerated with acceptable toxicity in combination with paclitaxel/carboplatin chemotherapy.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5966246/

Ruxolitinib synergistically enhances the anti-tumor activity ... Our results demonstrated for the first time that the combination of ruxolitinib with paclitaxel is more effective against ovarian cancer growth than either ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11551860/

An NRG Oncology Group Study In conclusion, ruxolitinib in combination with dose-dense paclitaxel plus carboplatin was well-tolerated and showed an improvement in PFS in up ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02713386?cond=%22Ovarian%20Clear%20Cell%20Adenocarcinoma%22&intr=%22albumin-bound%20paclitaxel%22&viewType=Table&rank=6&tab=results

Study Results | Ruxolitinib Phosphate, Paclitaxel, and ... Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

5. cancernetwork.com cancernetwork.com/view/ruxolitinib-plus-chemotherapy-as-pre-postsurgical-treatment-in-ovarian-cancer-appears-feasible

Ruxolitinib Plus Chemotherapy as Pre/Postsurgical ... Overall, 42 patients were treated with carboplatin and paclitaxel alone and 105 received additional ruxolitinib. Patient characteristics ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5516

Updated survival analysis from OVATION-2 trial. IMNN-001 demonstrated trends towards material improvement in overall survival and acceptable safety in advanced EOC, especially in HRD+ patients.

7. nature.com nature.com/articles/s41698-025-00947-0

Lestaurtinib's antineoplastic activity converges on JAK ... Combination of paclitaxel with rosiglitazone induces synergistic cytotoxic effects in ovarian cancer cells. Article Open access 28 December ...