Rucaparib + Nivolumab for Leiomyosarcoma

Not currently recruiting at 7 trial locations

Overseen By Sujana Movva, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, PARP inhibitors

Disqualifiers: CNS metastases, Autoimmune disease, 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: 1

Duration: Up to 104 weeks (26 cycles)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, rucaparib and nivolumab (also known as Opdivo), to determine their effectiveness in treating advanced or metastatic leiomyosarcoma, a cancer that starts in smooth muscles. The researchers aim to discover if this combination works as well as standard chemotherapy. Individuals with this specific cancer type who have tried up to three different treatments without success might be suitable candidates for the trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering hope to those seeking new options.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chemotherapy or investigational therapies, you must have completed them at least 3 weeks 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 the combination of rucaparib and nivolumab has been tested in patients with leiomyosarcoma, a cancer affecting smooth muscle tissue. In one study with 20 patients, the treatment was generally well-tolerated, but only 5% of patients experienced significant tumor shrinkage.

These results suggest that while the treatment can be effective for some, its impact may vary. Previous studies indicate that rucaparib and nivolumab work together uniquely by repairing damaged DNA and boosting the immune system to fight cancer cells.

This is a Phase 2 trial, meaning researchers have already collected initial safety data, suggesting the treatment is considered safe enough to test in a larger group. It is important to consult a healthcare provider to learn more about possible side effects and to decide if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Rucaparib and Nivolumab for treating leiomyosarcoma because it offers a novel approach compared to traditional treatments like chemotherapy and surgery. Rucaparib is a PARP inhibitor that targets cancer cells' ability to repair DNA damage, potentially enhancing the effectiveness of cancer cell destruction. Nivolumab, on the other hand, is an immunotherapy drug that helps the immune system recognize and attack cancer cells more effectively. This combination could provide a dual mechanism of action, offering a potentially more powerful treatment option for patients who may not respond well to existing therapies.

What evidence suggests that combining rucaparib and nivolumab might be an effective treatment for leiomyosarcoma?

This trial will evaluate the combination of rucaparib and nivolumab for treating leiomyosarcoma. Research has shown mixed results for this combination in treating leiomyosarcoma, a type of cancer. In a study with 20 patients, about 5% experienced tumor shrinkage, indicating that only a few patients responded to the treatment. This combination targets the DNA repair mechanisms of cancer cells, a promising area for cancer treatment. Although this method is new, it has not yet proven significantly better than treatments using immune checkpoint inhibitors (ICI) alone. However, this combination has shown positive results in treating other types of cancer, suggesting potential benefits for certain patient groups. ^{1 2 3 4 6}

Who Is on the Research Team?

Sujana Movva, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults (18+) with advanced or metastatic Leiomyosarcoma who have had 1-3 prior systemic therapies can join this trial. They must not have used PARP inhibitors or PD-1/PD-L1 antibodies before, and should be recovered from previous treatments' side effects. Participants need functioning major organs, measurable disease, and no active infections or significant heart issues. Women of childbearing potential must test negative for pregnancy and agree to contraception.

Inclusion Criteria

My liver function tests are within the required range.

My LMS cannot be removed by surgery and has spread.

I finished any cancer treatments at least 3 weeks ago, and my side effects are mild.

Exclusion Criteria

I do not have any other cancer that needs treatment or could affect this trial.

Subjects expecting to have a child within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after the last dose of study treatment(s) for women or 7 months for men.

I have a weakened immune system due to conditions like HIV, Hepatitis B/C, or autoimmune diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rucaparib and nivolumab. Rucaparib is taken orally twice daily, and nivolumab is administered intravenously on day 1 of each 28-day cycle.

Up to 104 weeks (26 cycles)

1 visit every 4 weeks for nivolumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with re-staging scans every 8 weeks.

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Rucaparib

Trial Overview The study is testing the combination of Rucaparib (a drug that targets cancer cells) and Nivolumab (an immunotherapy) in patients with Leiomyosarcoma to see if it's more effective than standard chemotherapy. Patients will receive both drugs as part of their treatment regimen.

How Is the Trial Designed?

Group I: Rucaparib in combination with Nivolumab Experimental Treatment 2 Interventions

One treatment cycle will consist of 28 days. Patients will receive rucaparib at 600 mg, orally, twice daily, continuously for 28 days. They will receive 480mg of nivolumab intravenously on day 1 of every four-week cycle. This is the recommended phase II dose of the combination therapy. Re-staging scans will be performed every 8 weeks. Treatment will be repeated until the patient develops progressive disease or unacceptable toxicity or for a maximum duration of 26 cycles as long as patients are receiving benefit from treatment, have not had disease progression, met any criteria for study withdrawal and are tolerating therapy.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a study of 41 patients with advanced metastatic leiomyosarcoma, combining PD-1 inhibitors with pegylated liposomal doxorubicin (PLD) and dacarbazine (DTIC) resulted in a higher overall response rate (30% vs. 4.8%) compared to chemotherapy alone, indicating some potential for improved initial response.

However, there were no significant differences in progression-free survival (PFS) or overall survival (OS) between the two treatment groups, suggesting that while the combination may enhance response rates, it does not translate into longer survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of PD-1 inhibitors combined with pegylated liposomal doxorubicin and dacarbazine compared with liposomal doxorubicin and dacarbazine in advanced leiomyosarcoma patients: a retrospective, single-institutional cohort study. Tan, Z., Wang, X., Liu, J., et al.[2022]

Management of leiomyosarcoma (LMS) is highly individualized, depending on factors like tumor location, whether the disease is localized or metastatic, and the resectability of the tumor.

For patients with recurrent or metastatic LMS, systemic chemotherapy is typically the first-line treatment, with options including anthracycline or gemcitabine regimens, and emerging therapies may be guided by tumor genomics for more personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leiomyosarcoma: Does Location of Primary Help to Determine the Best Systemic Therapy Options? Novotny, JP., George, S.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40514070/

Phase II study of rucaparib and nivolumab in patients with ... Phase II study of rucaparib and nivolumab in patients with leiomyosarcoma ... Results: 20 patients with LMS were enrolled. There was one ...

2. withpower.com withpower.com/trial/phase-3-leiomyosarcoma-10-2020-15b98?lat=34.60184&lng=-117.81218

Rucaparib + Nivolumab for Leiomyosarcoma There is no direct evidence supporting the effectiveness of Rucaparib + Nivolumab for leiomyosarcoma. However, targeting DNA damage repair pathways, which ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04624178

NCT04624178 | A Study of Rucaparib and Nivolumab in ... The purpose of this study is to find out whether combining the study drugs rucaparib and nivolumab may be an effective treatment for advanced and/or metastatic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12164637/

Phase II study of rucaparib and nivolumab in patients with ... The combination of rucaparib and nivolumab led to a 5% response rate among 20 patients with LMS, which is not an improvement over ICI alone, and ...

5. onclive.com onclive.com/view/nivolumab-rucaparib-combo-induces-clinically-effective-outcomes-in-subgroup-of-patients-with-mcrpc

Nivolumab/Rucaparib Combo Induces Clinically Effective ... The median OS among all patients was 20.2 months (95% CI, 14.1-22.8). The median OS in the 34 patients with HRD-positive tumors was 22.7 months ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-11422

A Study of Rucaparib and Nivolumab in Patients with ... Combining the drugs rucaparib and nivolumab may boost the immune system in patients with leiomyosarcoma to fight the cancer and prevent the growth of new cancer ...