Atezolizumab for Sarcoma

Not currently recruiting at 17 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Autoimmune disease, Severe infections, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of atezolizumab, an immunotherapy drug, in treating certain types of sarcoma that are newly diagnosed, inoperable, or have metastasized. Atezolizumab, a monoclonal antibody, may help the immune system attack cancer cells and prevent their growth and spread. The trial seeks participants with specific forms of sarcoma, such as chondrosarcoma or clear cell sarcoma, particularly those with worsening symptoms like increased tumor pain. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that you should not have taken certain treatments like systemic immunosuppressive medications within 2 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that atezolizumab is likely to be safe for humans?

Research has shown that atezolizumab, a medicine used in cancer treatment, is generally well-tolerated by patients. In studies involving individuals with the rare cancer alveolar soft part sarcoma, atezolizumab helped shrink tumors in about 40% of participants.

Regarding safety, atezolizumab has manageable side effects. Although specific safety information for patients with chondrosarcoma or clear cell sarcoma is lacking, its approval for other conditions suggests reasonable safety. However, patients might still experience side effects, so discussing potential risks with healthcare providers is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sarcoma?

Atezolizumab is unique because it is an immunotherapy that works by blocking a protein called PD-L1. This action helps the immune system recognize and attack cancer cells more effectively. Unlike traditional therapies for sarcoma, which often include surgery, chemotherapy, and radiation, atezolizumab offers a more targeted approach. Researchers are excited because this mechanism could lead to better outcomes with potentially fewer side effects, offering new hope for patients with this challenging condition.

What evidence suggests that atezolizumab might be an effective treatment for sarcoma?

Research has shown that atezolizumab, which participants in this trial will receive, has potential in treating certain sarcomas. In studies with advanced alveolar soft part sarcoma (ASPS), atezolizumab reduced tumor size in nearly 40% of patients. This success led to FDA approval for treating ASPS, highlighting its usefulness. Although chondrosarcoma and clear cell sarcoma differ, the success in ASPS suggests atezolizumab might also help the immune system combat these cancers. Early results indicate it could slow tumor growth and spread by enabling the body to attack cancer cells. ^{1 2 6 7 8}

Who Is on the Research Team?

A P Chen

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for children and teens aged 2-17 with clear cell sarcoma or advanced chondrosarcoma that's either new, can't be surgically removed, or has spread. They should have a life expectancy over 3 months, certain blood counts within range, measurable disease, and no major health issues that could affect the trial. They must not have had recent vaccines or antibiotics and cannot be pregnant.

Inclusion Criteria

My kidney function, measured by creatinine clearance, is adequate.

I have a specific type of cancer that is spreading and causing more symptoms.

Your hemoglobin (a protein in your blood) levels are at least 8 grams per deciliter (a unit of measurement for blood).

Exclusion Criteria

You cannot have participated in any other experimental treatment within the last 4 weeks (or within five half lives of the investigational product, whichever is shorter) before starting this study.

I do not have any unmanaged ongoing illnesses.

I have active tuberculosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab intravenously every 21 days, with CT scans, biopsies, and blood sample collections on study

Up to 3 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab

Trial Overview

The study tests Atezolizumab's effectiveness against specific sarcomas in young patients. It involves collecting biospecimens and using CT scans to monitor the cancer's response to this immunotherapy drug designed to boost the body’s immune system in fighting cancer cells.

How Is the Trial Designed?

Group I: Treatment (atezolizumab) Experimental Treatment 4 Interventions

Patients receive atezolizumab IV over 30-60 minutes on ay 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and undergo biopsy and collection of blood samples on study.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

In a phase 2 study involving 86 patients with advanced soft-tissue or bone sarcoma, pembrolizumab demonstrated some efficacy, particularly in undifferentiated pleomorphic sarcoma (40% response rate) and dedifferentiated liposarcoma (20% response rate), although the overall response rate did not meet the primary endpoint.

The treatment was associated with some serious adverse events, including immune-related conditions like adrenal insufficiency and pneumonitis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Tawbi, HA., Burgess, M., Bolejack, V., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2303383

Atezolizumab for Advanced Alveolar Soft Part Sarcoma

Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS.

2.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2023/atezolizumab-effective-alveolar-soft-part-sarcoma

Atezolizumab Shrinks Alveolar Soft Part Sarcomas - NCI

Treatment with atezolizumab (Tecentriq) shrank tumors in nearly 40% of people with alveolar soft part sarcoma, according to new clinical ...

3.

esmoopen.com

esmoopen.com/article/S2059-7029(23)01286-3/fulltext

Efficacy of immune checkpoint inhibitors in alveolar soft- ...

The results from this study (ORR 37%, median PFS 20.8 months) have granted the FDA approval of atezolizumab for patients with advanced ASPS.

4.

ascopubs.org

ascopubs.org/doi/10.1200/EDBK_432234

Immunotherapy in Sarcoma: Current Data and Promising ...

Atezolizumab demonstrated excellent results in ASPS achieving durable responses in one third of patients, leading to its FDA approval in this ...

5.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approvals-tecentriq-atezolizumab-unresectable-or-metastatic-alveolar

FDA D.I.S.C.O. Burst: Tecentriq and Krazati

The main efficacy outcome measures were overall response rate and duration of response determined by an independent review committee using ...

6.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-grants-approval-atezolizumab-alveolar-soft-part-sarcoma

FDA grants approval to atezolizumab for alveolar soft part ...

1. ORR was 24% (95% CI: 13, 39). Of the 12 patients who experienced an objective response, 67% had a DOR of 6 months or more, and 42% had a DOR ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11557

Safety and toxicity evaluation of the combination ...

We designed a randomized phase 2 study to evaluate atezolizumab with or without selinexor in adult patients with ASPS that included a safety run-in (SR) open ...

8.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK567758/

Atezolizumab - StatPearls - NCBI Bookshelf - NIH

Toxicity. There is no available data regarding the safety of atezolizumab in pediatric patients and pregnant or breastfeeding women.[12][11] ...