Talimogene Laherparepvec + Radiation Therapy for Soft Tissue Sarcoma

Recruiting at 17 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

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects of talimogene laherparepvec and radiation therapy and to see how well they work in treating patients with newly diagnosed soft tissue sarcoma that can be removed by surgery (resectable). Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Radiation therapy uses high energy x-rays, photons. electrons, or protons to kill tumor cells and shrink tumors. Giving talimogene laherparepvec and radiation therapy may work better in treating patients with soft tissue sarcoma.

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.

What data supports the effectiveness of this treatment for soft tissue sarcoma?

Research shows that advanced radiotherapy techniques like image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) have significantly improved the treatment of soft tissue sarcoma by enhancing local control of the tumor. Additionally, stereotactic body radiation therapy (SBRT) has been effective in controlling tumors in patients with limited metastases, achieving high control rates at treated sites. ^{1 2 3 4 5}

Is the combination of Talimogene Laherparepvec and radiation therapy generally safe for humans?

Research shows that combining stereotactic radiotherapy (a precise form of radiation therapy) with other treatments like immunotherapy can increase both effectiveness and side effects. Some studies have reported unexpected side effects, especially in the gastrointestinal system, when combining advanced radiation techniques with certain drugs. It's important to be aware of these potential risks when considering such treatments. ^{6 7 8 9 10}

What makes the treatment with Talimogene Laherparepvec and Radiation Therapy unique for soft tissue sarcoma?

This treatment is unique because it combines Talimogene Laherparepvec, a virus-based therapy that helps the immune system attack cancer cells, with various forms of radiation therapy to enhance the overall effectiveness against soft tissue sarcoma. This combination aims to improve tumor response by leveraging both direct cancer cell destruction and immune system activation. ^{11 12 13 14 15}

Research Team

Steven I. Robinson

Principal Investigator

Mayo Clinic Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Radiotherapy for soft tissue sarcoma: 50 years of change and improvement. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity. [2011]

4. England pubmed.ncbi.nlm.nih.gov

Phase II study of concomitant radiotherapy with atezolizumab in oligometastatic soft tissue sarcomas: STEREOSARC trial protocol. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity. [2022]

6. Poland pubmed.ncbi.nlm.nih.gov

Integrating stereotactic radiotherapy and systemic therapies. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Factors associated with radiation necrosis and intracranial control in patients treated with immune checkpoint inhibitors and stereotactic radiotherapy. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy. [2018]

9. France pubmed.ncbi.nlm.nih.gov

Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

The role of salvage reirradiation for malignant gliomas that progress on bevacizumab. [2022]

12. United States 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. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

MR-Guided Radiotherapy: The Perfect Partner for Immunotherapy? [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Micellar Formulation of Talazoparib and Buparlisib for Enhanced DNA Damage in Breast Cancer Chemoradiotherapy. [2020]

15. United States pubmed.ncbi.nlm.nih.gov

Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01). [2021]