Nivolumab + Chemotherapy for Soft Tissue Sarcoma

Not currently recruiting at 206 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: PD-1 inhibitors, PD-L1 inhibitors, VEGF TKIs, others

Disqualifiers: Autoimmune diseases, CNS metastases, 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 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of different treatments for soft tissue sarcoma, a cancer affecting the body's connective tissues. It tests combinations of nivolumab (Opdivo), a drug that helps the immune system fight cancer, with chemotherapy drugs like paclitaxel (Taxol, Onxol, or Abraxane), and cabozantinib, which may block cancer cell growth. The goal is to determine if these treatments can shrink the cancer and prevent its return. Individuals with angiosarcoma, a form of soft tissue sarcoma that cannot be cured with surgery and who have not previously used certain cancer drugs, may be eligible to join. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important cancer research.

Will I have to stop taking my current medications?

The trial requires that you stop taking strong inhibitors and inducers of CYP3A4 at least 7 to 14 days before starting the study. If you are on systemic steroid therapy, you must reduce the dose to 10 mg of prednisone or less per day at least 7 days before registration. Please consult with the study team for specific guidance on your medications.

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

Research has shown that the combination of nivolumab and paclitaxel is generally well-tolerated by patients with soft tissue sarcoma. Although the treatment did not achieve all its goals, it proved safe, with most patients not experiencing unexpected severe side effects.

For the nivolumab and cabozantinib combination, studies indicate it is safe and effective for patients with soft tissue sarcoma. Patients in these studies did not report any unexpected severe side effects, suggesting this treatment is also well-tolerated.

Both treatment combinations show promise, but side effects can occur. It is important to consult a doctor to understand the risks and benefits based on individual health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nivolumab and chemotherapy for soft tissue sarcoma because it introduces a novel approach by using an immunotherapy drug alongside traditional chemotherapy. Nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively, which is different from the typical chemotherapy treatments like doxorubicin that directly target and kill rapidly dividing cells. Additionally, the combination with paclitaxel could potentially enhance the overall effectiveness by targeting the cancer in multiple ways, improving outcomes for patients who may not respond well to existing treatments. This multi-faceted strategy gives hope for better control of the disease and improved survival rates.

What evidence suggests that this trial's treatments could be effective for soft tissue sarcoma?

In this trial, participants will join different treatment arms to evaluate the effectiveness of various combinations. A previous study found that paclitaxel helped shrink tumors in some patients with soft tissue sarcoma. Participants in one arm will receive paclitaxel alone. Another arm will test paclitaxel with nivolumab, although earlier studies did not show a noticeable improvement with this combination compared to paclitaxel alone. Meanwhile, another arm will explore nivolumab and cabozantinib, which have shown promising results in treating other types of cancer. Early signs suggest this combination might also be effective for soft tissue sarcoma, but more research is needed to confirm its efficacy. Overall, these treatments have potential, but their effectiveness can vary depending on the specific combination and type of cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Juneko E Grilley-Olson

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

Adults with certain types of soft tissue sarcoma who haven't had taxane drugs or are pre-treated with them. They must be in good health, not pregnant or nursing, and without serious heart issues or recent thromboembolic events. No history of severe autoimmune diseases, uncontrolled illnesses, or hypersensitivity to the trial drugs is allowed.

Inclusion Criteria

I am fully active or can carry out light work.

Your platelet count is at least 100,000 per cubic millimeter.

Your bilirubin levels must be within a certain range, unless you have Gilbert's disease, in which case a higher level is allowed.

Exclusion Criteria

I am not currently taking aspirin (more than 81 mg/day) or any blood thinners.

I haven't had any cancer except for skin cancer in the last 5 years.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment based on their assigned arm: nivolumab and paclitaxel, paclitaxel alone, or nivolumab and cabozantinib. Treatment cycles repeat every 4 weeks for up to 2 years.

Up to 24 months

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes imaging and clinical assessments.

Every 3 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Paclitaxel

Trial Overview The effectiveness of adding Nivolumab to chemotherapy (Paclitaxel) for patients new to taxane treatment and its combination with Cabozantinib for those previously treated. The study aims to see if these combinations can shrink tumors and prevent recurrence.

How Is the Trial Designed?

Group I: Arm III (nivolumab, cabozantinib S-malate) Experimental Treatment 8 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily. Cycles repeat every 4 weeks for up to 2 years (24 months) for patients who achieve CR, PR or SD on immunotherapy/nivolumab, or in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood at baseline and on study, CT scan, spiral CT, or MRI, or FDG-PET scan throughout the trial.

Group II: Arm II (paclitaxel) Experimental Treatment 7 Interventions

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood at baseline and on study, CT scan, spiral CT, or MRI, or FDG-PET scan throughout the trial.

Group III: Arm I (nivolumab, paclitaxel) Experimental Treatment 8 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 and paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 4 weeks for up to 2 years (24 months) for patients who achieve CR, PR or SD on immunotherapy/nivolumab, or in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood at baseline and on study, CT scan, spiral CT, or MRI, or FDG-PET scan throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 2 study involving 85 patients with metastatic sarcoma, the combination of nivolumab and ipilimumab showed a higher confirmed response rate (16%) compared to nivolumab alone (5%), indicating that the combination therapy may be more effective for certain sarcoma subtypes.

While both treatments had manageable safety profiles, serious treatment-related adverse events occurred in 19% of patients receiving nivolumab and 26% in those receiving the combination therapy, suggesting that while the combination is promising, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. D'Angelo, SP., Mahoney, MR., Van Tine, BA., et al.[2021]

Checkpoint inhibitor therapy, specifically ipilimumab and nivolumab, can lead to long-term remission in patients with advanced soft tissue sarcoma, even in cases with zero percent PD-L1 expression, suggesting efficacy regardless of this biomarker.

The combination of checkpoint inhibitors with treatments like cryoablation may enhance the effectiveness of immunotherapy, indicating a potential strategy for improving outcomes in soft tissue sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression. Zhou, M., Bui, N., Lohman, M., et al.[2021]

In a phase II trial involving 38 patients with advanced metastatic soft tissue sarcoma (STS) who had failed previous treatments, the combination of sintilimab (a PD-1 inhibitor) and doxorubicin showed a promising overall objective response rate of 39.5% and a disease control rate of 71.1%.

The treatment was found to be safe and well-tolerated, with manageable adverse events primarily being hematologic, and patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma experienced significantly longer progression-free survival compared to other subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sintilimab plus doxorubicin in advanced soft tissue sarcoma: A single-arm, phase II trial. Tian, Z., Dong, S., Zuo, W., et al.[2023]

A woman with non-small cell lung cancer developed a photodistributed dermatitis as a side effect of nab-paclitaxel therapy, which worsened with each treatment cycle, highlighting the potential for skin reactions in patients receiving taxane chemotherapy.

The patient's condition improved with topical corticosteroids and strict sun avoidance, indicating that while photodermatoses can occur with taxane treatments, they can be managed effectively without necessarily stopping chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel-associated photosensitivity: report in a woman with non-small cell lung cancer and review of taxane-related photodermatoses. Beutler, BD., Cohen, PR.[2020]

In a study of patients with advanced soft tissue sarcoma treated with the combination of ipilimumab and nivolumab, the objective response rate was 15%, with one complete response and five partial responses, indicating some level of efficacy.

The treatment was generally well tolerated, with a clinical benefit rate of 34% and a median overall survival of 12 months, although 58% of patients experienced adverse events, primarily mild, with a small percentage facing more severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab for soft tissue sarcoma: a single institution retrospective review. Zhou, M., Bui, N., Bolleddu, S., et al.[2021]

In a study of treatment-naive patients with PD-L1 positive metastatic soft tissue sarcomas, the combination of nivolumab and ipilimumab (NPI) significantly improved overall survival (12.2 months) and progression-free survival (4.1 months) compared to nivolumab alone (NIV), which had overall survival of 9.2 months and progression-free survival of 2.2 months.

While NPI showed greater efficacy in extending survival, it was associated with a higher incidence of severe adverse events (72.9% in NPI vs. 27.1% in NIV), indicating that while it may be more effective, it is also less tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab versus nivolumab in individuals with treatment-naive programmed death-ligand 1 positive metastatic soft tissue sarcomas: a multicentre retrospective study. Chen, Y., Liu, X., Liu, J., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04339738

NCT04339738 | Testing the Addition of Nivolumab to ... This trial is being done to see if the combination of nivolumab and paclitaxel or cabozantinib can shrink soft tissue sarcoma and possibly prevent it from ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9340935/

Cabozantinib combination therapy for the treatment of solid ... This review demonstrates the promising efficacy outcomes of cabozantinib combined with other therapies, and a safety profile similar to cabozantinib alone.

3. opdivohcp.com opdivohcp.com/efficacy/rcc/opdivo-cabometyx

OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib ... Nivolumab plus cabozantinib versus sunitinib for previously untreated advanced renal cell carcinoma: results from 55-month followup of the CheckMate 9ER trial.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03367741

Cabozantinib S-malate and Nivolumab in Treating Patients ... This randomized phase II trial studies how well cabozantinib s-malate and nivolumab work in treating patients with endometrial cancer that has come back ...

5. ijcrioncology.com ijcrioncology.com/archive/2023/pdf/100123Z10KS2023.pdf

Safe and effective use of cabozantinib and nivolumab in ... Conclusion: These cases demonstrate the safety and efficacy of using combination nivolumab and cabozantinib in treatment of STS warranting ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8393686/

Novel Insights into the Immunotherapy of Soft Tissue ... Nivolumab is currently being evaluated for the treatment of STSs mostly in combination therapies (clinicaltrial.gov). Nivolumab monotherapy was tested in ...

7. repositoriosaludmadrid.es repositoriosaludmadrid.es/bitstreams/042a9aef-a472-4072-959e-9ac95797b7a4/download

Cabozantinib combination therapy for the treatment of solid ... Findings from randomized studies suggested that cabozantinib combined with other therapies may lead to better progression-free survival than some current ...