Open Label Study of Everolimus (RAD001) in Patients With Segmental Overgrowth Syndrome

NCT02569125 | Withdrawn Phase 2

• 2 other identifiers: CRAD001CDE40T2014-004019-35
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, multicenter, single-arm, phase II clinical trial of Everolimus (RAD001) in patients with segmental overgrowth syndrome.

Conditions

Segmental Overgrowth Syndrome

Keywords

segmental overgrowth syndrome

Outcome Measures

Primary Outcomes (1)

• Number of patients with partial or complete response measured by MRI.

  until 12 months

Study Arms (1)

Everolimus (RAD001) 4.5 mg/m² daily over

EXPERIMENTAL

Everolimus (RAD001) 4.5 mg/m² daily over 12 months. Patients will be on Everolimus (RAD001) therapy for 12 months; discontinuation can be necessary due to intolerable toxicity, withdrawal of consent, death or termination of the trial. After 12 months treatment is stopped. If there is progress of disease (see below) after end of therapy, re-start with Everolimus (RAD001) on a compassionate use is possible.

Drug: Everolimus

Interventions

Everolimus DRUG

4.5 mg/m² daily

Also known as: Votubia

Everolimus (RAD001) 4.5 mg/m² daily over

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 1 years.
• Signed written informed consent (patient older than 18 years or person(s) having the care and custody of the patient younger than 18 years).
• Segmental overgrowth syndrome patients independently of genetic background (that means with/ without PTEN germline mutations or with/without AKT/PI3K somatic mutations in an overgrowth lesion).
• Patients who meet clinical criteria for segmental overgrowth syndromes, including a soft tissue lesion composed of one or several tissue components such as fat, vessels, muscle, muscle or connective tissue.
• Identification of a target lesion by MRI \> 5 cm3. The target lesion must be externally visible (photos) and composed by soft tissue.
• Normal organ and bone marrow function (i.e. transaminase levels \> 2.5 x ULN or serum bilirubin \> 1.5 x ULN, hemoglobin \> 9 g/dL).
• Negative urine pregnancy test in females with a childbearing potential.
• If female and of child-bearing potential, documentation of negative pregnancy test prior to enrollment. Sexually active female patients (and female partners of male patients) must use adequate contraceptive measures while on study and for up to 8 weeks after ending treatment.

You may not qualify if:

• Any concurrent therapy with chemotherapy agents or biologic agents or radiation therapy.
• Patients who have received live vaccines in the past 30 days prior to informed consent.
• Patients on medication with CYP3A4 inhibitors / inducers which are not replaced by other equivalent medications for the study period.
• Patients who have known immunodeficiency or HIV seropositivity.
• Patients with known interstitial lung disease, pneumonitis or with bleeding diathesis.
• Patients with prior use of Everolimus or other mTOR inhibitors such as f.e. Rapamycin or any analogue within the last 6 months; regardless of therapeutic effect, but with risk assessment due to former side effects.
• Any planned surgery within study period.
• Pre-existing chronic wounds.
• Triglycerides \> 400 mg/dL (\> 4.5 mmol/L) or total cholesterol \> 300 mg/dL (\> 7.8 mmol/L).
• Creatinine clearance ≤ 60 mL/min (Cockcroft and Gault formula).
• Proteinuria ≥ 30 mg/dL on dipstick and 24 hours proteinuria \> 0.8 g/24 hours.
• Intake of St John's Wort and/or grapefruit and grapefruit juice.
• Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks:
• Uncontrolled hypercholesterolemia/hypertriglyceridemia.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome).

Sponsors & Collaborators

• Jochen Roessler: lead
• Clinical Trials Unit Freiburg: collaborator

Study Sites (4)

Vivantes Klinikum Neukölln

Berlin, 12351, Germany

Location

Universitätsklinikum Bonn

Bonn, 53113, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

MeSH Terms

Interventions

Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jochen Roessler, Professor

  University Hospital Freiburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating Investigator

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: October 6, 2015
• Study Start: January 1, 2016
• Primary Completion: January 1, 2016
• Study Completion: February 1, 2016
• Last Updated: September 28, 2017

Record last verified: 2017-09

Locations

DE (4)