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

• Status: Withdrawn
• Trial end date: 2016-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jochen Roessler
• Collaborator: Clinical Trials Unit Freiburg
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria:

1. Male or female patients aged ≥ 1 years.

2. Signed written informed consent (patient older than 18 years or person(s) having the care and custody of the patient younger than 18 years).

3. 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).

4. 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.

5. Identification of a target lesion by MRI > 5 cm3. The target lesion must be externally visible (photos) and composed by soft tissue.

6. 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).

7. Negative urine pregnancy test in females with a childbearing potential.

8. 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.

Exclusion Criteria:

1. Any concurrent therapy with chemotherapy agents or biologic agents or radiation therapy.

2. Patients who have received live vaccines in the past 30 days prior to informed consent.

3. Patients on medication with CYP3A4 inhibitors / inducers which are not replaced by other equivalent medications for the study period.

4. Patients who have known immunodeficiency or HIV seropositivity.

5. Patients with known interstitial lung disease, pneumonitis or with bleeding diathesis.

6. 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.

7. Any planned surgery within study period.

8. Pre-existing chronic wounds.

9. Triglycerides > 400 mg/dL (> 4.5 mmol/L) or total cholesterol > 300 mg/dL (> 7.8 mmol/L).

10. Creatinine clearance ≤ 60 mL/min (Cockcroft and Gault formula).

11. Proteinuria ≥ 30 mg/dL on dipstick and 24 hours proteinuria > 0.8 g/24 hours.

12. Intake of St John's Wort and/or grapefruit and grapefruit juice.

13. 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).

14. Patients with a known hypersensitivity to Everolimus or other mTOR inhibitors such as f.e. Rapamycin or any analogs or to its excipients.

15. Patients unwilling to or unable to comply with the planned therapeutic intervention or to comply with the study treatment visits including blood sample collection within the protocol.

16. Female patients who are pregnant or breast feeding, or patients of reproductive potential who are not using effective birth control methods. If barrier contraceptives are used, they must be continued throughout the study by both sexes.