Phase I study of Everolimus combined with Metformin for patients with advanced cancer

Completed

• Conditions: for which no standard treatment is available/ various types of cancer for which no standard treatment is available; various malignancies; 10027655

• Registration Number: NL-OMON39171
• Lead Sponsor: Academisch Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

- Signed informed content obtained prior to treatment
- Cytological or histological confirmed malignancies
- ECOG/ WHO performance 0-2
- Age > 18 years
- Life expectancy of at least 3 months
- Adequate renal function (creatinine < 150 µmol/L and/ or a creatinine clearance > 60 ml/ L)
- Adequate liver function (bilirubin < 1.5 times upper limit of normal, * 3 × ULN for patients known to have Gilbert Syndrome, ALAT or ASAT < 5.0 times upper limit of normal in case of liver metastases and < 2.5 the upper limit of normal in absence of liver metastases).
- Fasting serum cholesterol * 7.75 mmol/L and fasting triglycerides * 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy or other lipid lowering drugs (eg fibrates), and when the above mentioned values have been achieved.
- Adequate bone marrow function ((Absolute neutrophil count (ANC * 1.5 109/L ,platelets > 100 x 10 9/L)
- Mentally, physically, and geographically able to undergo treatment and follow up

Exclusion Criteria

- Pregnancy (positive serum pregnancy test) and lactation
- Serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
- Patients who have any severe and/or uncontrolled medical conditions such as:
unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction * 6 months prior to randomization, serious uncontrolled cardiac arrhythmia, active or uncontrolled severe infection, cirrhosis, chronic active hepatitis or chronic persistent hepatitis (see screening for hepatitis Appendix A), severely impaired lung function
- Uncontrolled diabetes as defined by fasting serum glucose >2X ULN.
- Patients with a known hypersensitivity to metformin
- Use of metformin in the previous 6 months
- Patients that have received everolimus in the past
- Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin)
-Concomitant use of strong CYP3A4, 3A5 and 2C8 inhibitors or inducers (see section 2.1.12

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint: assessment of the dose limiting toxicity (DLT) and the<br /><br>maximal tolerated dose (MTD) of the combination of everolimus and metformin.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br>- Efficacy: response rate in patients with measurable disease<br /><br>- Safety: treatment toxicity<br /><br>- Exploratory endpoint: iInvestigation of potential biomarker development based<br /><br>on assessment of skin biopsies and blood samples </p><br>