Talimogene Laherparepvec + Radiation Therapy for Soft Tissue Sarcoma

Recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants, Immunosuppressants, Antivirals, others

Disqualifiers: Metastatic disease, Autoimmune disease, 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

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for soft tissue sarcoma, a cancer affecting tissues like muscle or fat. The study combines talimogene laherparepvec, a biological therapy that boosts the immune system, with radiation therapy to target and shrink tumors before surgery. It aims to determine the effectiveness and safety of these treatments when used together. Individuals with newly diagnosed soft tissue sarcoma in the arms, legs, or trunk, scheduled for surgical removal, may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for autoimmune diseases or are receiving systemic immunosuppressive therapy, you may not be eligible to participate.

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

Earlier studies have shown that talimogene laherparepvec, or T-VEC, is safe. Research indicates that most patients tolerate T-VEC well. Some may experience mild side effects like fever, chills, or fatigue, but these are usually short-lived and manageable.

Radiation therapy, commonly used for various cancers, is also considered safe. It can cause side effects such as skin irritation and fatigue, which often improve after treatment ends.

The goal of combining T-VEC with radiation therapy is to enhance treatment effectiveness without introducing significant new risks. Clinical trials are essential to confirm this. Current evidence suggests both treatments are safe, and healthcare professionals will closely monitor participants during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for soft tissue sarcoma, which often rely on surgery, chemotherapy, and radiation, talimogene laherparepvec offers a unique approach. This treatment uses a modified herpes simplex virus to selectively infect and destroy cancer cells while sparing healthy tissue. Researchers are excited about this method because it not only directly targets tumor cells but also stimulates the immune system to recognize and attack other cancer cells throughout the body. This dual action has the potential to enhance the effectiveness of radiation therapy, offering a promising new avenue for patients with soft tissue sarcoma.

What evidence suggests that talimogene laherparepvec and radiation therapy might be effective for soft tissue sarcoma?

Research has shown that injecting talimogene laherparepvec directly into tumors can help treat certain cancers by boosting the immune system to attack cancer cells. Studies have found that this treatment can shrink tumors and slow their growth, even in advanced cancer cases. In this trial, participants will receive talimogene laherparepvec combined with radiation therapy. Radiation therapy uses high-energy rays to kill cancer cells and is commonly used for soft tissue sarcomas. Combining talimogene laherparepvec with radiation therapy might lead to better results, as the two treatments can work together to destroy cancer cells more effectively. ^{1 3 6 7 8}

Who Is on the Research Team?

Steven I. Robinson

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with newly diagnosed, potentially removable soft tissue sarcoma of the extremity or trunk (like liposarcoma or leiomyosarcoma) that's larger than 5 cm and requires radiation before surgery. Participants need normal organ function, no prior cancer treatments causing unresolved side effects, no metastatic disease, not pregnant/breastfeeding, and must agree to use contraception.

Inclusion Criteria

I have a newly diagnosed, operable soft tissue sarcoma in my limbs or trunk.

I am willing to give a tissue sample during surgery for the study.

Platelets >= 100,000/uL

Exclusion Criteria

I have a viral infection.

My cancer has spread to other parts of my body.

Patients who are pregnant, breastfeeding or plan to become pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talimogene laherparepvec intratumorally or via intralesional injection at weeks 1, 4, 6, and 8, and undergo radiation therapy Monday-Friday of weeks 2-6

8 weeks

Weekly visits for injections and daily visits for radiation during weeks 2-6

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy
• Talimogene Laherparepvec

Trial Overview The trial is testing talimogene laherparepvec combined with radiation therapy on patients who can have their tumors surgically removed. It aims to see if this combination is more effective in treating soft tissue sarcomas compared to standard therapies.

How Is the Trial Designed?

Group I: Treatment (talimogene laherparepvec, radiation therapy) Experimental Treatment 5 Interventions

Patients receive talimogene laherparepvec IT or via intralesional injection at weeks 1, 4, 6 and 8. Beginning 1 week after the start of talimogene laherparepvec, patients undergo radiation therapy on Monday-Friday of weeks 2-6. Patients undergo collection of blood and a tumor biopsy on study and undergo MRI throughout the trial.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

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 II study of 46 patients with locally advanced rectal cancer, a sequential schedule of administering bevacizumab before chemotherapy resulted in a 50% rate of complete tumor regression, significantly higher than the 12.5% observed with the concomitant schedule.

The sequential schedule also showed a lower incidence of severe neutropenia (30% vs. 44%) and fewer postoperative complications (28% vs. 53%), indicating a potentially safer and more effective treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial. Avallone, A., Pecori, B., Bianco, F., et al.[2022]

In a study of 179 patients with non-small cell lung cancer, renal cell carcinoma, or melanoma treated with immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS), the combination showed a low local failure rate of 5.8%, suggesting effective intracranial control when these treatments are used together.

Higher PD-L1 expression (≥50%) was linked to increased rates of grade 2+ radiation necrosis (17% vs. 3%), indicating that while the combination therapy is generally safe, patients with high PD-L1 levels may need closer monitoring for potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with radiation necrosis and intracranial control in patients treated with immune checkpoint inhibitors and stereotactic radiotherapy. Hall, J., Lui, K., Tan, X., et al.[2023]

The combination of stereotactic body radiation therapy (SBRT) with targeted biologic agents, especially those that inhibit angiogenesis, has shown promise in cancer treatment but has also led to unexpected late gastrointestinal toxicities.

Understanding the biological mechanisms behind these toxicities is crucial for safely expanding the use of SBRT and antiangiogenic therapies in clinical practice, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy. Pollom, EL., Deng, L., Pai, RK., et al.[2018]

In a study of 59 patients with brain metastases from non-small-cell lung cancer and melanoma, the timing between immunotherapy and stereotactic radiotherapy (SRT) did not significantly affect the local control of tumors or the incidence of severe toxicities.

The main predictor of toxicity was tumor volume, with only 5.1% of patients experiencing grade 3 or higher toxicities, indicating that SRT combined with immunotherapy is generally safe regardless of the timing of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases. Cabanie, C., Biau, J., Durando, X., et al.[2021]

In a study of 74 patients with metastatic renal cell carcinoma, adding stereotactic body radiotherapy (SBRT) to non-first-line PD-1 inhibitors and targeted agents significantly improved overall survival, with a median of 38.5 months compared to 15.4 months for those receiving only anti-PD-1/TA therapy.

The combination of SBRT with anti-PD-1/TA therapy was found to be safe and tolerable, with a similar rate of severe toxicities (54.8% in the SBRT group vs. 65.6% in the anti-PD-1/TA alone group), suggesting that this approach could be beneficial for patients, especially those with clear-cell type renal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma. Liu, Y., Zhang, Z., Liu, R., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7693687/

Radiation Therapy in Adult Soft Tissue Sarcoma—Current ... This review summarizes the current evidence for RT in adult STS including typical indications, outcomes, side effects, dose and fractionation regimens, and ...

2. thegreenjournal.com thegreenjournal.com/article/S0167-8140(22)02276-9/abstract

Long-term outcomes after definitive radiotherapy with ... The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce.

3. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02346-w

Treatment outcomes of stereotactic body radiation therapy for ... Purpose. This study evaluated the treatment outcomes of spine stereotactic body radiation therapy (SBRT) in sarcoma patients.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814022022769

Long-term outcomes after definitive radiotherapy with ... In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients.

5. practicalradonc.org practicalradonc.org/article/S1879-8500(21)00118-1/fulltext

Radiation Therapy for Treatment of Soft Tissue Sarcoma in ... Treatment guidelines for preoperative radiation therapy for retroperitoneal sarcoma: Preliminary consensus of an international expert panel

6. sciencedirect.com sciencedirect.com/science/article/pii/S2452109422002299

Efficacy and Safety of Stereotactic Body Radiation Therapy ... Limited data are currently available on clinical outcomes after stereotactic body radiation therapy (SBRT) for pediatric and adolescent and young adult ...

7. practicalradonc.org practicalradonc.org/article/S1879-8500(21)00118-1/pdf

Executive Summary of an ASTRO Clinical Practice Guideline Methodology—The task force uses evidence-based methodologies to develop guideline recommendations in accordance with the National Academy of Medicine standards.

8. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02255-y

Treatment outcomes of stereotactic body radiation therapy for ... The aim of this study was to evaluate the treatment outcomes and potential dose-response relationship of stereotactic body radiation therapy ...