What side effects are associated with this type of intervention?

Common treatments for Soft Tissue Sarcoma (STS) include immune checkpoint inhibitors like Pembrolizumab and targeted high-dose radiation such as Stereotactic Ablative Radiotherapy (SBRT). Pembrolizumab can cause a range of immune-related adverse events (irAEs), including myositis, inflammatory arthritis, and vasculitis, which can occasionally be severe or fatal. SBRT, on the other hand, may lead to acute and chronic toxicities, such as skin reactions, fatigue, and potential damage to surrounding tissues. Combining these treatments can enhance efficacy but also increases the risk of compounded side effects.

What prior FDA approvals exist?

For the treatment of Soft Tissue Sarcoma (STS), the FDA has approved several therapies, including immune checkpoint inhibitors like Pembrolizumab for patients with high levels of microsatellite instability (MSI-H). While Pembrolizumab is being studied in combination with Stereotactic Ablative Radiotherapy (SBRT) in clinical trials, its use in STS remains investigational for broader patient populations. Other treatments for STS include traditional chemotherapy agents, but the combination of immune checkpoint inhibitors and targeted high-dose radiation like SBRT is still under investigation and not yet a standard FDA-approved treatment for STS.

What other types of research exist?

Promising novel alternatives for Soft Tissue Sarcoma patients include mTOR inhibitors like everolimus and temsirolimus, which have shown efficacy in various sarcoma subtypes. Tyrosine kinase inhibitors such as sunitinib and regorafenib are also potential options, demonstrating positive outcomes in phase II trials. Additionally, the combination of doxorubicin and bevacizumab has been explored with some success. These alternatives offer different mechanisms of action and may provide effective treatment options for STS patients.

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Checkpoint Inhibitor

Pembrolizumab + Radiotherapy for Sarcoma

Q: What is the mechanism of action of this treatment?

Immune checkpoint inhibitors like pembrolizumab work by blocking proteins such as PD-1 on immune cells, which cancer cells often exploit to avoid being attacked by the immune system. This reactivates the immune response against cancer cells, potentially leading to tumor reduction. Stereotactic ablative radiotherapy (SBRT) delivers high doses of radiation precisely to the tumor site, minimizing damage to surrounding healthy tissue and effectively shrinking or destroying the tumor. These treatments are significant for STS patients as they offer targeted approaches that can enhance the body's natural defenses and precisely target tumors, potentially improving outcomes and reducing side effects compared to traditional therapies.

Phase < 1

Recruiting

Led By Jeremy Harris, MD, MPhil

Research Sponsored by University of California, Irvine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of a drug that helps the immune system fight cancer and a precise form of radiation therapy. It targets patients with soft-tissue sarcoma whose cancer has spread or cannot be cured with surgery. The drug boosts the immune system, and the radiation targets tumors directly.

Who is the study for?

Adults with advanced or recurrent soft-tissue sarcoma, not eligible for curative surgery. Must have measurable lesions, life expectancy over 3 months, and proper organ/marrow function. HIV-positive patients can join if viral load is undetectable. Excludes pregnant/nursing women, those on active immunosuppression, with recent chemotherapy/radiotherapy or other investigational agents.

What is being tested?

The trial tests the combination of pembrolizumab (an immunotherapy drug) and stereotactic ablative radiotherapy (SBRT) in treating metastatic sarcoma. It aims to see if this combo is feasible for patients who've had previous systemic therapy or are ineligible for it.

What are the potential side effects?

Pembrolizumab may cause immune-related side effects like inflammation in various organs, skin reactions, hormonal gland problems leading to hormone deficiencies, infusion reactions and potential harm to a fetus; SBRT might cause localized pain or skin changes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Feasibility, measured as the number of patients completing treatment.

Secondary study objectives

Duration of response

Local failure at the irradiated site

Number of grade 3-5 adverse events

+6 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: B: Radiation Therapy with or without standard of care checkpoint inhibitor immunotherapyExperimental Treatment1 Intervention

Patients who are currently receiving a checkpoint inhibitor immunotherapy regimen will be allowed to continue their regimen at their treating oncologist's discretion. Radiation therapy will be delivered in 1 to 10 fractions starting on Day 1.

Group II: A: Pembrolizumab + Radiation TherapyExperimental Treatment2 Interventions

Patients receive pembrolizumab 400 mg intravenous every 42 days; Radiation therapy in 1 to 10 fractions.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Radiation therapy

2013

Completed Phase 3

~2850

Pembrolizumab

2017

Completed Phase 3

~3150

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immune checkpoint inhibitors like pembrolizumab work by blocking proteins such as PD-1 on immune cells, which cancer cells often exploit to avoid being attacked by the immune system. This reactivates the immune response against cancer cells, potentially leading to tumor reduction. Stereotactic ablative radiotherapy (SBRT) delivers high doses of radiation precisely to the tumor site, minimizing damage to surrounding healthy tissue and effectively shrinking or destroying the tumor. These treatments are significant for STS patients as they offer targeted approaches that can enhance the body's natural defenses and precisely target tumors, potentially improving outcomes and reducing side effects compared to traditional therapies.

Soft tissue sarcomas in the precision medicine era: new advances in clinical practice and future perspectives.