Navtemadlin + Radiation for Soft Tissue Sarcoma

Recruiting at 57 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, Factor Xa inhibitors

Disqualifiers: Pregnancy, Cardiac conditions, Metastatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 10-13 weeks

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the effects of navtemadlin and radiation therapy in patients with soft tissue sarcoma. Navtemadlin helps stop cancer cells from growing, and radiation therapy kills them with high-energy x-rays. The goal is to shrink the tumor before surgery to remove less normal tissue. Navtemadlin is a newer drug being tested for its ability to stop cancer cells from growing.

Do I need to stop taking my current medications for the trial?

The trial requires participants to stop using herbal medicines and certain medications that affect liver enzymes (CYP3A4 and CYP2C8 substrates) within 10-14 days before starting the trial and during the first 5 weeks of treatment. You will need to provide a list of medications you are taking to the trial team.

What data supports the effectiveness of the treatment Navtemadlin + Radiation for Soft Tissue Sarcoma?

Research shows that combining radiation therapy with targeted agents can improve local control and survival in soft tissue sarcomas by enhancing the effectiveness of radiation through biological pathway modulation. Additionally, modern radiation techniques have improved efficacy and reduced side effects, making them a valuable part of treatment strategies for soft tissue sarcomas. ^{1 2 3 4 5}

Is the combination of Navtemadlin and radiation therapy safe for humans?

Research on radiation therapy for soft tissue sarcomas shows it generally has low toxicities and is safe, with some risk of skin reactions and wound complications. However, specific safety data for Navtemadlin combined with radiation therapy is not available in the provided studies. ^{6 7 8 9 10}

What makes the drug Navtemadlin unique for treating soft tissue sarcoma?

Navtemadlin is unique because it combines with radiation therapy to potentially enhance the treatment's effectiveness against soft tissue sarcoma, a condition with limited standard treatment options. This combination aims to improve outcomes by targeting specific molecular pathways involved in cancer cell survival and growth. ^{2 3 11 12 13}

Research Team

Meng X Welliver

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with intermediate or high-grade soft tissue sarcoma larger than 5 cm, aiming for curative treatment. Participants must have no history of other cancers (with some exceptions), not be pregnant or breastfeeding, and cannot have metastatic disease. They should not have had chemotherapy or radiotherapy for the sarcoma before and must agree to avoid certain medications during the trial.

Inclusion Criteria

My treatment goal is to cure my disease.

I am scheduled for surgery to remove my primary tumor and can care for myself with minimal assistance.

I can provide samples of my tumor for testing.

Exclusion Criteria

I've had radiation in the same area where my current cancer is located.

I cannot take pills due to my GI condition.

I have not needed IV antibiotics for an infection in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive navtemadlin and undergo radiation therapy for 5 weeks, followed by surgery 5-8 weeks after RT completion

10-13 weeks

Daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

2.5 years

Every 3 months for 2 years, then at 2.5 years

Treatment Details

Interventions

• KRT-232
• Navtemadlin
• Radiation Therapy

Trial Overview The study tests navtemadlin combined with radiation therapy in patients with soft tissue sarcoma. Navtemadlin blocks enzymes that cancer cells need to grow, while radiation aims to kill tumor cells. The goal is to shrink tumors before surgery.

Participant Groups

Group I: Step 2, Group II (radiation therapy, surgery) Experimental Treatment 2 Interventions

Starting with week 2, patients undergo radiation therapy daily for 5 weeks in the absence of disease progression or unacceptable toxicity, followed by surgery 5-8 weeks after RT completion.

Group II: Step 2, Group I (navtemadlin, radiation therapy, surgery) Experimental Treatment 3 Interventions

Starting with week 2, patients receive navtemadlin as in Step 1 and undergo RT daily for 5 weeks in the absence of disease progression or unacceptable toxicity, followed by surgery 5-8 weeks after RT completion.

Group III: Step 1 (tumor tissue testing, navtemadlin) Experimental Treatment 2 Interventions

Patients undergo tumor tissue testing for p53 gene status and receive navtemadlin PO on days 2-4, days 2-5, or days 1-5 of weeks 1 to 5 in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

In a study of 59 patients with extremity soft tissue sarcomas, intensity-modulated radiotherapy (IMRT) resulted in late toxicities in 75% of patients, with the majority being mild to moderate (G1-2), including functional limitations and chronic pain.

A larger volume of healthy soft tissue surrounding the treatment area (greater than 3500 cm³) was associated with reduced late toxicities, suggesting that careful planning of radiotherapy can help minimize side effects for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume? Bourdais, R., Achkar, S., Honoré, C., et al.[2022]

Postoperative intensity-modulated radiation therapy (IMRT) for patients with soft tissue sarcomas (STSs) in the extremities and trunk wall resulted in an impressive 5-year local control rate of 88.1%, especially for patients with negative surgical margins (90% local control) compared to those with positive margins (64.8%).

The treatment demonstrated low toxicity, with only 17.6% of patients experiencing edema and 9.8% experiencing joint stiffness, indicating that IMRT is a safe and effective option for managing STSs post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative intensity-modulated radiation therapy provides favorable local control and low toxicities in patients with soft tissue sarcomas in the extremities and trunk wall. Wang, J., Wang, S., Song, Y., et al.[2020]

In a phase II study involving 52 patients with high-risk primary soft tissue sarcoma, a 5-day neoadjuvant radiotherapy regimen resulted in a low rate of grade ≥2 late radiation toxicity (16%) and a 32% incidence of major wound complications.

The study identified a potential germline biomarker that could predict major wound complications, which may help improve the safety and effectiveness of radiotherapy in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma. Kalbasi, A., Kamrava, M., Chu, FI., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Radiation Therapy in Adult Soft Tissue Sarcoma-Current Knowledge and Future Directions: A Review and Expert Opinion. [2020]

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

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma. [2022]

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

Combining targeted agents with modern radiotherapy in soft tissue sarcomas. [2021]

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

Chemotherapy of sarcomas. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Phase II evaluation of amonafide in advanced sarcoma: a Southwest Oncology Group study. [2020]

6. Ireland pubmed.ncbi.nlm.nih.gov

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume? [2022]

7. England pubmed.ncbi.nlm.nih.gov

Incidence and correlates of radiation dermatitis in children and adolescents receiving radiation therapy for the treatment of paediatric sarcomas. [2009]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Postoperative intensity-modulated radiation therapy provides favorable local control and low toxicities in patients with soft tissue sarcomas in the extremities and trunk wall. [2020]

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

A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma. [2021]

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

Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma. [2022]

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

Radiation-induced sarcoma. [2019]

12. Germany pubmed.ncbi.nlm.nih.gov

[Radiotherapeutic strategies for soft tissue sarcomas in adults]. [2006]

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

Radiation-induced sarcoma following radiotherapy for testicular tumor. [2019]