Phase I study of RAD001 (Everolimus) in combination with Fluvastatin and Zoledronic acid in patients with solid tumours

Phase 1

Active, not recruiting

• Conditions: Advanced cancers; Cancer - Any cancer

• Registration Number: ACTRN12612000136808
• Lead Sponsor: St George Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-01-31
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Histologic or cytologic diagnosis of a solid tumour.
No curative treatment options available.
Evidence of locally advanced or metastatic disease. This can be measurable, evaluable, or nonmeasurable.
Up to three prior chemotherapy regimens for advanced disease is permitted.
No chemotherapy (hormonal therapy excluded) for at least 4 weeks before enrollment in study (6 weeks for mitomycin or nitrosoureas).
WHO Performance Status 0 - 2.
Estimated life expectancy of at least 12 weeks.
Prior radiation therapy is allowed provided no more than 30% of bone marrow producing areas have been irradiated and patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Radiation therapy must have been completed at least 2 weeks prior to commencing study treatment.
Prior bisphosphonate therapy is allowed, but any previous zoledronic acid must have been administered no more frequently than once a month. Prior HMGCoA reductase therapy for hypercholesterolemia is allowed, but patients should be willing to change to fluvastatin on trial.
Adequate organ function including the following:
Adequate bone marrow reserve: absolute neutrophil count (ANC) greater or less than 1.5 × 109/L, platelets greater or less than 100 × 109/L, hemoglobin greater or less than 9 g/dL.
Hepatic: bilirubin greater than 2 times upper limit of normal (× ULN), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) greater than 3.0 × ULN (ALP, AST, and ALT greater than 5 × ULN is acceptable if liver has tumor involvement). NB, if LFTs meet the criteria for RAD001 dose reduction at study enrolment, the dose of RAD001 will be halved in the first instance.
Renal: serum creatinine greater than 0.16 mmol/l or creatinine clearance greater than 60ml / min
Signed informed consent.
Minimum age 18 years.
Patients on study with reproductive potential, or with female partners with reproductive potential, must use an effective contraceptive method during the trial and for 3 months after the study.

Exclusion Criteria

1] Patients receiving another investigational drug
2] Active infection or chronic infection. This includes bacterial, as well as fungal and viral infections. Patients with HIV, Viral Hepatitis of any sort (including carriers) are excluded in view of the potential for immunosuppresion with RAD001
3] Uncontrolled brain metastases. Patients with meningeal metastases are eligible.
4] Pregnancy or breast-feeding.
5] Serious concomitant medical or psychiatric disorders which would compromise the safety of the patient or their ability to complete the study, at the discretion of the investigator.
6] Significant cardiovascular disease: unstable angina, myocardial infarction within 3 months or significant cardiac failure.
7] Patitents on medications potentially a substrate for CYP3A4 (see Appendix 3) are eligible if they are able to stop the relevant medication prior to study entry. However, patients unable to stop their medications (other than a HMGCoA reductase inhibitor) are ineligible. It is not known whether fluvastatin is a substrate for CYP3A4, so patients who are willing to change their HMGCoA reductase inhibitor to fluvastatin are eligible.

Study & Design

• Study Type: Interventional
• Study Design: Not specified