45 Participants Needed

Miransertib for Proteus Syndrome

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CA
LG
Overseen ByLeslie G Biesecker, M.D.
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: National Human Genome Research Institute (NHGRI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using certain experimental therapies or those with uncontrolled diabetes requiring regular medication. It's best to discuss your specific medications with the trial team.

What makes the drug Miransertib unique for treating Proteus Syndrome?

Miransertib is unique for treating Proteus Syndrome because it targets a specific pathway involved in the overgrowth of tissues, which is a hallmark of this condition. Unlike other treatments, it directly inhibits the AKT1 enzyme, which is part of the signaling pathway that contributes to the abnormal cell growth seen in Proteus Syndrome.12345

What is the purpose of this trial?

Background:Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome.Objective:To learn if miransertib is a safe and effective treatment for Proteus syndrome.Eligibility:People ages 3 and older with Proteus syndrome.Design:Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study.Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug.Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome.Participants will have lung function tests to measure how much and how fast air moves out of their lungs.Participants will complete surveys about their levels of pain, physical functioning, and quality of life.Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists.Participation lasts about 4 years. Participants will have 20-30 visits at the NIH....

Research Team

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Leslie G Biesecker, M.D.

Principal Investigator

National Human Genome Research Institute (NHGRI)

Eligibility Criteria

This trial is for people aged 3 and older with Proteus syndrome, a rare overgrowth disorder. Participants must have specific blood values within normal ranges, not use tobacco or certain drugs, and agree to contraception if of childbearing potential. They can't join if they have uncontrolled diabetes, significant heart issues, active infections, or intolerance to AKT inhibitors like miransertib.

Inclusion Criteria

I am between 3 and 16 years old with a measurable foot tumor and a body surface area of at least 0.33 m^2.
Agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse while on study and for up to 90 days after ending treatment
I am over 3 years old, have used or am using miransertib, and my body surface area is at least 0.33 m^2.
See 7 more

Exclusion Criteria

I do not have any severe illnesses unrelated to Proteus syndrome.
I have diabetes that is not well-controlled with medication other than metformin.
I haven't had serious heart problems in the last 6 months.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive miransertib in continuous, 28-day cycles, with dose escalation based on tolerance

Up to 52 cycles (approximately 4 years)
20-30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a final clinical safety follow-up 30 days after the last dose

30 days

Long-term monitoring

Participants may continue to be monitored for long-term safety and effectiveness

Ongoing

Treatment Details

Interventions

  • Miransertib (ARQ092)
  • MK-7075 (Miransertib)
Trial Overview The trial tests the safety and effectiveness of MK-7075 (miransertib) in slowing down or stopping overgrowth in Proteus syndrome patients. It involves taking daily pills of miransertib for about four years with regular checkups at NIH including medical exams, imaging scans, lung function tests and surveys on pain and quality of life.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: MK-7075 (miransertib)Experimental Treatment1 Intervention
This is a single-arm study. All study participants will be taking the experimental drug, MK-7075 (miransertib).

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Human Genome Research Institute (NHGRI)

Lead Sponsor

Trials
273
Recruited
299,000+

Findings from Research

In a study of 66 patients with recurrent malignant glioma, the maximum tolerated dose (MTD) of bortezomib was found to be 1.70 mg/mยฒ for those not taking enzyme-inducing anti-seizure drugs, while the dose could not be escalated beyond 2.5 mg/mยฒ for those who were, indicating that these drugs affect bortezomib's tolerability.
The study showed that bortezomib effectively inhibited the 20S proteasome, achieving a plateau of around 79% inhibition in patients not on anti-seizure drugs, and some clinical activity was observed with two partial responses, suggesting potential efficacy in treating high-grade gliomas.
Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma.Phuphanich, S., Supko, JG., Carson, KA., et al.[2018]
Bortezomib, the first proteasome inhibitor approved for clinical use in 2003, has shown significant efficacy in treating advanced multiple myeloma, with about one third of patients experiencing clinical benefits in trials.
The drug works by inhibiting the proteasome, leading to apoptosis of cancer cells and reduced tumor growth through mechanisms like nuclear factor-kappa B inhibition and activation of c-Jun N-terminal kinase.
Proteasome inhibition as a novel therapeutic target in human cancer.Rajkumar, SV., Richardson, PG., Hideshima, T., et al.[2015]
In a phase II study involving 12 patients with metastatic breast cancer, PS-341 (bortezomib) showed no objective tumor responses, indicating it was ineffective for this condition.
All patients in the study experienced disease progression while on PS-341 treatment, leading to the early termination of the trial due to lack of efficacy.
A phase II study of single agent bortezomib in patients with metastatic breast cancer: a single institution experience.Engel, RH., Brown, JA., Von Roenn, JH., et al.[2015]

References

Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma. [2018]
Proteasome inhibition as a novel therapeutic target in human cancer. [2015]
A phase II study of single agent bortezomib in patients with metastatic breast cancer: a single institution experience. [2015]
CCR 20th anniversary commentary: In the beginning, there was PS-341. [2019]
Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma. [2021]
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