What side effects are associated with this type of intervention?

Common treatments for Soft Tissue Sarcoma (STS) include enzyme inhibitors like Navtemadlin and radiation therapy. Enzyme inhibitors can cause side effects such as fatigue, nausea, and potential myotoxicity. Radiation therapy often leads to skin irritation, fatigue, and localized pain. When combined, these treatments may enhance each other's efficacy but also compound side effects. Other common treatments like chemotherapy can cause nausea, hair loss, and increased risk of infection, while targeted therapies may lead to hypertension, proteinuria, and skin rashes.

What prior FDA approvals exist?

The FDA has approved several treatments for soft tissue sarcoma that involve enzyme inhibition and radiation therapy. For instance, the mTOR inhibitor nab-sirolimus has been approved for locally advanced unresectable or metastatic malignant PEComa, a subtype of soft tissue sarcoma. Additionally, radiation therapy using high-energy x-rays is a common treatment modality for various types of soft tissue sarcomas, often used in combination with chemotherapy or targeted therapies to enhance efficacy. While specific enzyme inhibitors like navtemadlin are still under investigation, the combination of targeted enzyme inhibition and radiation therapy represents a promising approach in the treatment landscape of soft tissue sarcomas.

What other types of research exist?

Promising novel alternatives for soft tissue sarcoma treatment include investigational agents such as regorafenib, cabozantinib, sorafenib, and lenvatinib plus etoposide and ifosfamide. These agents have shown some limited activity in clinical trials and may offer new therapeutic options for patients.

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MDM2 Inhibitor

Navtemadlin + Radiation for Soft Tissue Sarcoma

Phase 1

Waitlist Available

Led By Meng X Welliver

Research Sponsored by National Cancer Institute (NCI)

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 2.5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include typical reactions from radiation like skin irritation and fatigue, as well as possible effects from navtemadlin such as nausea, vomiting, diarrhea, changes in blood counts leading to increased risk of infections or bleeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2.5 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

Maximum Tolerated Dose (MTD) / Recommended Phase 2 Dosage for Each Cohort

Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)

Secondary study objectives

Number of Participants Who Died

Number of Participants With Disease or Death From Any Cause

Number of Participants With Local Failure

+3 more

Other study objectives

Tumor Volume Changes

mdm2/4 Expression

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Step 2, Group II (radiation therapy, surgery)Experimental Treatment2 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 Treatment3 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 Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Surgical Procedure

2020

Completed Phase 2

~160

Radiation Therapy

2017

Completed Phase 3

~7250

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

The most common treatments for Soft Tissue Sarcoma (STS) include enzyme inhibition and radiation therapy. Enzyme inhibitors, like Navtemadlin, block specific enzymes essential for cancer cell growth, thereby halting tumor proliferation. Radiation therapy employs high-energy x-rays to damage the DNA of cancer cells, preventing their replication and leading to cell death. These mechanisms are vital for STS patients as they guide the selection of effective treatment strategies, aiming to improve outcomes and reduce side effects.

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