Nab-Sirolimus + Pazopanib for Soft Tissue Sarcoma

Overseen By Roxanne Moore

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Washington

Must be taking: Pazopanib

Must not be taking: mTOR inhibitors, Angiogenesis inhibitors

Disqualifiers: CNS metastases, Severe hepatic impairment, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles, up to 41 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, nab-sirolimus (sirolimus albumin-bound nanoparticles) and pazopanib (pazopanib hydrochloride), to evaluate their effectiveness and potential side effects in people with advanced non-adipocytic soft tissue sarcomas. These treatments aim to halt cancer cell growth by blocking essential enzymes. The trial seeks participants whose sarcoma has spread and who have not responded to previous treatments. Participants should have soft tissue sarcomas not located in fat tissue and have experienced disease progression despite earlier treatments. As a Phase 1, Phase 2 trial, this study focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial protocol does not clearly specify if you need to stop taking your current medications. However, you must not use strong inhibitors or inducers of CYP3A4 or any known CYP3A4 substrates with a narrow therapeutic window within 14 days before starting the trial. It's best to discuss your current medications with the trial team.

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

Studies have shown that pazopanib is generally safe for patients with soft tissue sarcoma. One study found that 14% of patients stopped taking it due to side effects, with the most common issues being fatigue, changes in liver tests, and diarrhea. Fortunately, no severe side effects were reported.

Research on nab-sirolimus suggests it is also safe. Trials have demonstrated its effectiveness for certain cancers and a promising safety record. Earlier studies have used it with pazopanib without major safety concerns.

Overall, both treatments appear well-tolerated based on past studies, though some side effects are possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about nab-sirolimus and pazopanib for treating soft tissue sarcoma because of their unique mechanisms. Unlike most treatments that target the tumor broadly, nab-sirolimus utilizes albumin-bound nanoparticles to deliver sirolimus directly to the cancer cells, potentially enhancing its effectiveness while minimizing side effects. Pazopanib, on the other hand, is a tyrosine kinase inhibitor that interferes with specific proteins involved in tumor growth and blood vessel formation. This combination targets the cancer more precisely, offering a promising new approach compared to the existing standard therapies.

What evidence suggests that nab-sirolimus and pazopanib could be effective for soft tissue sarcoma?

This trial will evaluate the combination of nab-sirolimus and pazopanib hydrochloride for treating soft tissue sarcomas. Research has shown that nab-sirolimus may offer significant benefits, as it helped shrink tumors in some patients in previous studies. One study found it particularly beneficial for malignant PEComa. Pazopanib hydrochloride has also shown promise for soft tissue sarcomas, with a 46.3% response rate in clinical trials, and some sarcoma types responded especially well. Overall, these treatments have shown potential in managing advanced soft tissue sarcomas, making them promising options for further research. ^{2 4 6 7 8}

Who Is on the Research Team?

Lee Cranmer

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults (18+) with advanced nonadipocytic soft tissue sarcomas not suitable for surgery or curative treatments, who haven't had more than four systemic therapies. Participants must have manageable cholesterol and triglyceride levels, normal heart function, adequate blood counts, and no major organ dysfunction. They should not be pregnant or breastfeeding and must agree to use effective contraception.

Inclusion Criteria

Hemoglobin >= 9 g/dL.

Serum cholesterol =< 350 mg/dL.

Ability to understand and sign informed consent.

Exclusion Criteria

I don't have major stomach or bowel issues that could affect medication absorption.

My brain metastases are controlled, not currently treated with steroids, and I finished any brain treatment over 28 days ago.

My diabetes is not under control, with HbA1c levels over 8% despite treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nab-sirolimus intravenously on days 1 and 8 or day 1 only and pazopanib hydrochloride orally daily on days 1-21. Cycles repeat every 21 days until disease progression or unacceptable toxicity.

21-day cycles, up to 41 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 30 days, then every 12 weeks.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Pazopanib hydrochloride
• Sirolimus Albumin-bound Nanoparticles

Trial Overview The trial is testing the combination of nab-sirolimus (a drug that targets cancer cell growth) with pazopanib hydrochloride (which blocks enzymes needed for tumor growth) in patients with advanced soft tissue sarcoma. The study aims to determine the best dose and assess how well these drugs work together.

How Is the Trial Designed?

Group I: Treatment (ABI-009, pazopanib) Experimental Treatment 2 Interventions

Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Aadi Bioscience, Inc.

Industry Sponsor

Trials

18

Recruited

580+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11635658/

Pazopanib in the real-world setting in soft tissue sarcomas Efficacy data in the PALETTE trial showed infrequent objective responses (partial response was observed in 6% of patients on pazopanib versus 0% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8414075/

Real-World Outcome and Prognostic Factors of Pazopanib ... Pazopanib is an effective treatment for STS. However, it showed variability in the clinical outcome in favor of ASPS and an outstanding response in the DT/AF ...

3. spandidos-publications.com spandidos-publications.com/10.3892/ol.2024.14848

Response rates of pazopanib therapy in metastatic soft ... The clinical response rate was 46.3%. Patients with hemangioendothelioma and alveolar soft part sarcoma exhibited an improved response to treatment.

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2020/pazopanib-votrient-soft-tissue-sarcoma-children-adults

Pazopanib Shows Promise for Soft Tissue Sarcomas - NCI Among the 42 patients remaining in the study at the time results were analyzed, 14 of 24 (58%) in the pazopanib group versus 4 of 18 (22%) in ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e23542

Pazopanib in metastatic soft tissue sarcoma (STS) The median follow-up under PAZ treatment was 5.03 (0.10-84.67) months. Objective response and disease control rates were 31.4% and 42.2%, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6691522/

Safety and efficacy of Pazopanib in advanced soft tissue ... A definitive treatment discontinuation due to AEs related to pazopanib occurred in 14% of patients [2]. However, limited data have been ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2468294220301106

Safety and efficacy of pazopanib as a second-line ... Pazopanib is a safe and effective tyrosine kinase inhibitor used in managing soft tissue sarcomas (STS) after chemotherapy failure. However, its use is limited ...

8. eortc.org eortc.org/blog/2011/11/27/pazopanib-improves-progression-free-survival-in-adults-with-certain-soft-tissue-sarcomas-2/

Pazopanib Improves Progression Free Survival In Adults ... The study showed a 69% reduction in the risk of progression or death in patients who received pazopanib compared to those who received placebo.