Nivolumab + Ipilimumab for Uterine Cancer

No longer recruiting at 1 trial location

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active autoimmune disease, Brain metastasis, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 92 weeks for Cohort A, 12 weeks for Cohort B

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drugs nivolumab and ipilimumab, used alone or together, in treating uterine cancer that has spread and resists other treatments. Both medications are monoclonal antibodies that may help prevent cancer cells from growing and spreading. Individuals with uterine cancer that has spread, cannot be surgically removed, and have undergone at least one prior chemotherapy treatment might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the study drugs. 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 nivolumab is generally well-tolerated by patients with uterine cancer. One study found it effective and safe for those with a specific genetic issue affecting DNA repair. Another review found that nivolumab helped control the disease in 76.9% of patients with advanced endometrial cancer.

The combination of nivolumab and ipilimumab also appears safe. Trials have demonstrated significant benefits with manageable side effects. This combination is known to improve survival in some cancers, with side effects usually being manageable.

In summary, both nivolumab alone and with ipilimumab have been studied and are generally safe for patients. While side effects can occur, they are often manageable, which is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about nivolumab and ipilimumab for uterine cancer because these treatments harness the power of the immune system to fight cancer cells. Unlike traditional chemotherapy, which attacks cancer cells directly, these drugs are immunotherapy agents that work by blocking proteins that prevent the immune system from attacking cancer cells. Nivolumab is a PD-1 inhibitor, and ipilimumab is a CTLA-4 inhibitor; together, they enhance the body's ability to detect and destroy cancer cells more effectively. This approach offers a new avenue for treating uterine cancer, potentially leading to better outcomes and fewer side effects compared to conventional therapies.

What evidence suggests that nivolumab and ipilimumab could be effective for uterine cancer?

Research has shown that nivolumab, which participants in this trial may receive, can help treat certain types of endometrial cancer. In some studies, 80% of patients experienced a complete response, meaning their cancer became undetectable. Another study found that 76.9% of patients achieved disease control, where their cancer did not worsen. In this trial, some participants will receive a combination of nivolumab and ipilimumab. This combination has shown promise for treating cervical cancer that has recurred or spread, with a 36% overall response rate. It also helped patients live longer and reduced symptom worsening compared to other treatments. These findings suggest that nivolumab, alone or with ipilimumab, could be effective for uterine cancer that has spread. ^{1 3 6 7 8}

Who Is on the Research Team?

Suzanne George

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with advanced uterine leiomyosarcoma, a type of cancer that has spread and is typically incurable. Participants must have had at least one prior chemotherapy treatment, be in good physical condition (ECOG 0 or 1), and not be pregnant or breastfeeding. They should not have active brain metastases, severe allergies to monoclonal antibodies, HIV/AIDS, hepatitis B/C infection, uncontrolled illnesses, or a history of certain autoimmune diseases.

Inclusion Criteria

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)

Platelets >= 100,000/mcL

My cancer is a type of uterine cancer that has spread or cannot be surgically removed.

Exclusion Criteria

Patients who are receiving any other investigational agents

History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab

History of severe hypersensitivity reaction to any monoclonal antibody

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab alone or in combination with ipilimumab. Cohort A receives nivolumab every 2 weeks for up to 46 doses. Cohort B receives nivolumab and ipilimumab every 21 days for up to 4 courses.

Up to 92 weeks for Cohort A, 12 weeks for Cohort B

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study tests the effectiveness of Nivolumab alone or combined with Ipilimumab—both are monoclonal antibodies—in treating advanced uterine leiomyosarcoma. The trial aims to see how these treatments affect tumor growth and spread by targeting specific pathways within the body's immune system.

How Is the Trial Designed?

Group I: Cohort B (nivolumab and Ipilimumab) Experimental Treatment 2 Interventions

Patients receive nivolumab IV over approximately 60 minutes followed by a saline flush and ipilimumab IV over 90 minutes. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Group II: Cohort A (nivolumab - closed to accrual on 21-Oct-2015) Experimental Treatment 2 Interventions

Patients receive nivolumab IV over approximately 60 minutes once every 2 weeks for up to 46 doses in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. onclive.com onclive.com/view/nivolumab-yields-high-clinical-cr-rates-allowing-for-surgery-omission-in-dmmr-msi-h-endometrial-cancer

Nivolumab Yields High Clinical CR Rates Allowing for ... Nivolumab achieved an 80% clinical complete response rate in resectable dMMR/MSI-H endometrial cancer, with many patients avoiding surgery. No ...

2. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(25)00154-2/fulltext

Real World Multi-centre UK Review of Nivolumab ... Checkpoint inhibitor monotherapy with nivolumab brought disease control rates of 76.9% in this multi-centre UK metastatic endometrial cancer MMR ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11049060/

Systematic Review on the Effectiveness and Outcomes of ... With a median follow-up time of 19.2 months, the median overall survival (OS) was reported at 21.9 months, and the 12-month PFS rate was 26.3%, ...

4. esmo.org esmo.org/oncology-news/nivolumab-achieves-high-orr-and-durable-pfs-in-patients-with-dmmr-msi-h-recurrent-endometrial-or-ovarian-cancer

Nivolumab Achieves High ORR and Durable PFS in ... The authors concluded that the study met its co-primary endpoints of ORR and PFS24 early, and the findings highlight several genetic and tumour ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655525001542

Real World Multi-centre UK Review of Nivolumab ... Checkpoint inhibitor monotherapy with nivolumab brought disease control rates of 76.9% in this multi-centre UK metastatic endometrial cancer MMR-deficient ...

6. targetedonc.com targetedonc.com/view/nivolumab-shows-promising-efficacy-in-dmmr-uterine-and-ovarian-cancers

Nivolumab Shows Promising Efficacy in dMMR Uterine and ... A phase 2 trial demonstrated that nivolumab is effective and has a manageable safety profile in patients with mismatch repair deficiency uterine

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6823884/

Safety and Efficacy of Nivolumab Monotherapy in ... In CheckMate 358, nivolumab showed promising activity in a small cohort of five patients with recurrent/metastatic vaginal/vulvar cancers, with ...

8. nature.com nature.com/articles/s41591-024-02942-7

Nivolumab for mismatch-repair-deficient or hypermutated ... We conducted a single-arm phase 2 study of nivolumab in 35 patients with dMMR uterine or ovarian cancers. Co-primary endpoints included objective response rate ...