Immunotherapy Combined With Radiotherapy for Metastatic Sarcoma

NCT05488366 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: UCI 21-03 [HS# 978]978
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study determining the feasibility of combination treatments, pembrolizumab and stereotactic ablative radiotherapy (SBRT) in subjects with soft-tissue sarcoma. These are subjects who have metastatic disease initially, or recurrent or progressive disease that is not eligible for curative surgery.

Conditions

Sarcoma, Soft Tissue

Keywords

Sarcoma; Advanced Sarcoma; Metastatic Sarcoma; Pembrolizumab; Stereotactic Ablative Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Feasibility, measured as the number of patients completing treatment.

  Number of patients completing treatment with at least one cycle of pembrolizumab and completion of RT (Arm A) or completion of RT (Arm B). Up to 6 replacements are allowed (total subjects 6-12)

  Up to 3 years

Secondary Outcomes (9)

• Overall response rate (ORR) at non-irradiated sites

  Up to 3 years.

• Local failure at the irradiated site

  Up to 3 years

• Duration of response

  Up to 3 years

• Progression-free survival

  Up to 3 years.

• Overall survival

  Up to 3 years

Study Arms (2)

A: Pembrolizumab + Radiation Therapy

EXPERIMENTAL

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

Drug: Pembrolizumab; Radiation: Radiation therapy

B: Radiation Therapy with or without standard of care checkpoint inhibitor immunotherapy

EXPERIMENTAL

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.

Radiation: Radiation therapy

Interventions

Pembrolizumab DRUG

Given IV

Also known as: MK-3475

A: Pembrolizumab + Radiation Therapy

Radiation therapy RADIATION

Single target will be selected by the treating radiation oncologist. A lesion causing symptoms or expected to become symptomatic will be favored for target selection.

Also known as: RT

A: Pembrolizumab + Radiation Therapy; B: Radiation Therapy with or without standard of care checkpoint inhibitor immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed soft-tissue sarcoma, or a soft-tissue sarcoma with tumor mutational burden ≥10 mut/Mb.
• Patient must either have started a checkpoint inhibitor immunotherapy regimen within 60 days, or have a soft-tissue sarcoma histology amenable to pembrolizumab therapy (inclusive of undifferentiated pleomorphic sarcoma \[formerly known as malignant fibrous histiocytoma\], myxofibrosarcoma, dedifferentiated liposarcoma or undifferentiated sarcoma \[unclassified histology\]).
• Patients with soft-tissue sarcoma must have advanced disease (stage IV) or previously treated disease that has become progressive, recurrent, or metastatic, and either previously received first-line systemic therapy or been deemed ineligible to receive first-line systemic therapy. Staging is by AJCC 8th Edition.
• Must not have disease amenable to curative intent surgery.
• Must have at least 2 measurable lesions per RECIST v1.1 assessed by CT scan. A measurable lesion is defined to mean at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Must have at least 1 site of non-central nervous system (CNS) disease amenable to treatment with radiation therapy. This lesion may have been previously treated with radiation if the cumulative spinal cord dose will remain below a Biologically Effective Dose (BED)α/β 2Gy of 112 Gy (single fraction equivalent 14 Gy) and the radiation will be delivered at least 180 days after completion of the prior radiation course to the same site. BED will be calculated using the linear-quadratic formula: d \* f \* (1 + \[d / (α/β)\]), where d is the dose per fraction, f is the total number of fractions, and α/β is the property of irradiated tissue measured in Gray.
• Must be age ≥ 18 years. Because initial and subsequent therapies for pediatric sarcomas (\<18 years of age) are different than those ≥18, children are excluded from this study. In addition, because no adverse event data are currently available on the use of SBRT combined with pembrolizumab in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.
• \. Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, deaf, hard of hearing and illiterate individuals are eligible for this trial
• Performance status: ECOG performance status ≤2 (Karnofsky ≥50%).
• Life expectancy of ≥3 months.
• Adequate organ and marrow function as defined below. Labs should be performed within 14 days of treatment.
• Leukocytes ≥2,000/mcL
• Absolute neutrophil count ≥1,000/mcL
• Platelets ≥75,000/mcL
• AST(SGOT)/ALT(SPGT) ≤3 times institutional upper limit of normal (ULN), or ≤5 times ULN for patients with liver metastases

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to initiation of study therapy.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy administered.
• Patients must not be receiving any other investigational agents.
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Pembrolizumab can cause fetal harm when administered to a pregnant woman based on the biological mechanism that PD-1/PD-L1 signaling is an important pathway in the maintenance of pregnancy through induction of maternal immune tolerance to fetal tissue.1 Human IgG4 is known to cross the placenta. Animal models have found that blocking PD-L1 signaling increases the risk of fetal loss, and immune-mediated disorders occurred in PD-1 knockout mice.
• Although there are not data on the presence of pembrolizumab in either animal or human milk or its effects on breastfed children or on milk production, there is a potential for serious adverse reactions in breastfed children. Thus, women are advised not to breastfeed during treatment with pembrolizumab and for 120 days after the final dose.
• Patients with disease amenable to curative intent surgery.
• Patient has had a prior monoclonal antibody for treatment of sarcoma, unless the current regimen is checkpoint inhibitor immunotherapy.
• Patient has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin.
• Patient has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with resolved childhood asthma, hypothyroidism stable on hormone replacement, Sjogren's syndrome, or with vitiligo would not be excluded. Patients requiring intermittent bronchodilators, inhaled steroids, or local steroid injections would not be excluded. Patients requiring physiologic doses of corticosteroids may be approved after consultation with the protocol principal investigator.

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

Related Publications (1)

• Harris JP, Park J, Ku E, Seyedin S, Stitzlein R, Goldin A, Chen WP, McLaren C, Chen AM, Chow W. A Pilot Study of Pembrolizumab Combined With Stereotactic Ablative Radiotherapy for Patients With Advanced or Metastatic Sarcoma. Cancer Control. 2024 Jan-Dec;31:10732748241237331. doi: 10.1177/10732748241237331.

  PMID: 38449377 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Jeremy Harris, MD, MPhil

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor

Study Record Dates

• First Submitted: August 1, 2022
• First Posted: August 4, 2022
• Study Start: August 3, 2022
• Primary Completion: June 27, 2025
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)