What side effects are associated with this type of intervention?

Common treatments for sarcoma, such as MEK inhibitors (e.g., Selumetinib), investigational drugs, and PD-L1 inhibitors (e.g., Durvalumab), have a range of side effects. MEK inhibitors frequently cause rash, diarrhea, fatigue, and peripheral edema. Investigational drugs can lead to nausea, fatigue, and hematologic toxicities. PD-L1 inhibitors are associated with immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of sarcoma, including targeted therapies and immunotherapies. Pazopanib, a tyrosine kinase inhibitor, is approved for advanced soft tissue sarcoma. Additionally, the combination of pembrolizumab (a PD-1 inhibitor) and other agents has shown efficacy in certain sarcoma subtypes. While Selumetinib (a MEK inhibitor) and Durvalumab (a PD-L1 inhibitor) are being investigated in clinical trials for sarcoma, they have not yet received FDA approval specifically for this indication. These investigational approaches aim to expand the therapeutic options for patients with refractory or unresectable sarcomas.

What other types of research exist?

Promising alternatives for sarcoma treatment in 2024 include: 1) Pazopanib, a tyrosine kinase inhibitor, which has shown activity in various sarcoma subtypes. 2) Pembrolizumab, a PD-1 inhibitor, which has demonstrated efficacy in metastatic sarcomatoid renal cell carcinoma and is being investigated in other sarcoma types. 3) Nivolumab plus Ipilimumab, a combination of checkpoint inhibitors, which is suggested for metastatic Merkel cell carcinoma and may have potential in sarcoma. 4) Investigational approaches such as somatostatin receptor-based therapy and other novel agents in clinical trials.

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Kinase Inhibitor

Combination Therapy for Sarcoma

Phase 2

Waitlist Available

Research Sponsored by University of Alabama at Birmingham

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must be ≥ 18 years of age

Patients must have histologically confirmed soft tissue or bone sarcoma of specific subtypes

Must not have

Patients with severely impaired lung function or specific cardiac conditions

Patients who cannot swallow whole pills

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of three drugs to treat adults with hard-to-treat sarcomas, especially a type called MPNST linked to NF1. The drugs work together to stop cancer growth and boost the immune system. The study aims to find out if this combination is safe and effective. The combination of panobinostat, venetoclax, and anti-CD40 has shown promise in preclinical models for inducing complete tumor remission.

Who is the study for?

Adults (18+ years) with specific sarcomas, including MPNST and no standard treatment options left. They must have measurable disease, be over 30 kg in weight, recovered from previous treatments' side effects, not used certain inhibitors or immunosuppressants recently, and have proper organ function. Women of childbearing potential must use effective birth control.

What is being tested?

The trial is testing Selumetinib combined with a Bromodomain Inhibitor and Durvalumab on patients with refractory/unresectable sarcomas. It's an open-label phase 1/2 study where all participants receive the experimental drugs to see how well they work and what the side effects are.

What are the potential side effects?

Potential side effects may include skin rash, eye problems like blurred vision or dry eyes due to Selumetinib; fatigue, nausea from Bromodomain Inhibitors; immune-related reactions such as inflammation of organs or infusion-related symptoms from Durvalumab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My cancer is a specific type of sarcoma in the soft tissue or bone.

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I am using reliable birth control and my pregnancy tests are negative.

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I am using or willing to use birth control or have stored sperm before starting the treatment.

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My condition hasn't improved with standard treatments or there are no treatments available for it.

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I weigh more than 30 kilograms.

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My kidney function, heart's pumping ability, and heart rhythm are normal.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe lung problems or heart conditions.

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I cannot swallow whole pills.

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I have used immunosuppressive medications.

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I have had cancer before, but it meets the trial's specific conditions.

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I have had cancer spread to the lining of my brain and spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determine the Clinical Benefit of Selumetinib, BI and Durvalumab

Safety and Tolerability Selumetinib with BI

Safety and Tolerability of Durvalumab with Selumetinib and BI

Side effects data

From 2012 Phase 2 trial • 37 Patients • NCT01085214

75%

Diarrhea

50%

Fatigue

47%

Anemia

47%

Rash acneiform

44%

Hypoalbuminemia

44%

Edema, limbs

39%

Aspartate aminotransferase increased

33%

Neutrophil count decreased

33%

White blood cell decreased

31%

Nausea

31%

Vomiting

28%

Platelet count decreased

25%

CPK increased

25%

Hypomagnesemia

22%

Hypertension

19%

Hypophosphatemia

19%

Hyponatremia

19%

Hypocalcemia

19%

Edema, face

17%

Dry skin

17%

Alanine aminotransferase increased

14%

Skin and subcutaneous tissue disorders - Other

14%

Hypokalemia

14%

Creatinine increased

14%

Back pain

14%

Dyspnea

14%

Lymphocyte count decreased

11%

Pain

11%

Fever

11%

Localized edema

11%

Peripheral sensory neuropathy

11%

Hyperkalemia

11%

Dizziness

11%

Abdominal pain

Anorexia

Hypoglycemia

Acute kidney injury

Death, NOS

Periorbital edema

Skin hypopigmentation

Pain in extremity

Cough

Insomnia

Alkaline phosphatase increased

Dry mouth

Sepsis

Blood and lymphatic system disorders - Other

Hypernatremia

Metabolism and nutrition disorders - Other

Renal and urinary disorders - Other

Hypercalcemia

Dehydration

Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis

Chills

Hypotension

Myalgia

Arthralgia

Upper respiratory infection

Headache

Sinusitis

Generalized muscle weakness

Gastrointestinal disorders - Other

Gastroesophageal reflux disease

Vaginal inflammation

Confusion

Pruritus

Febrile neutropenia

Flu like symptoms

Hepatic failure

Skin infection

Fall

Fracture

Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral

Adult respiratory distress syndrome

Renal and urinary disorders - Other, Acute renal failure

INR increased

100%

80%

60%

40%

20%

Study treatment Arm

AZD6244 (Selumetinib) Treatment

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Phase 1 and 2 Study of Selumentinib, BI and DurvalumabExperimental Treatment1 Intervention

Part A will be a phase 1 dose escalation study of the combination with selumetinib and BI, and, Part B will be phase 1 study combining the determined dose of selumetinib and BI from Part A with durvalumab. Part C will be a phase 2 study combining selumetinib, BI with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Selumetinib

2010

Completed Phase 2

~2080

0 / 12Eligibility criteria met

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

Selumetinib, a MEK inhibitor, works by blocking the MEK enzyme in the MAPK/ERK pathway, which is often overactive in cancer cells, leading to reduced tumor growth and proliferation. Investigational drugs like BI may target specific molecular abnormalities or pathways unique to sarcoma cells, offering a tailored approach to treatment. Durvalumab, a PD-L1 inhibitor, enhances the immune system's ability to recognize and destroy cancer cells by blocking the PD-L1 protein that tumors use to evade immune detection. These mechanisms are crucial for sarcoma patients as they provide targeted therapies that can potentially improve outcomes by directly interfering with cancer cell growth and enhancing immune response, offering hope for more effective and personalized treatment options.

Stress Granules in the Anti-Cancer Medications Mechanism of Action: A Systematic Scoping Review.Targeted therapies for gallbladder cancer: an overview of agents in preclinical and clinical development.Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group.