Dose-finding Study of CAELYXTM and RAD001 in Patients With Advanced Solid Tumors
Recruitment status was Active, not recruiting
This is a dose finding, open-label, uncontrolled, dose-escalation trial to determine the Maximum Tolerated Dose (MTD) and the Recommended Dose (RD) of the combination RAD001 (escalating daily dose) and CaelyxTM (fixed dose) to patients with advanced solid tumors.
Other purposes of the study are:
- define the safety profile of the combination after repeated administrations
- define hints of antitumor activity, to be confirmed in subsequent disease-oriented expansion phases at the RD.
- define the pharmacokinetic profile of the combination
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Dose-finding Study of CAELYXTM and RAD001 in Patients With Advanced Solid Tumors|
- Maximum Tolerated Dose (MTD) and Recommended Dose (RD) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]The Maximum Tolerated Dose (MTD) is defined as the dose in which 2 of 3 or 2 of 6 patients experience a Dose Limiting Toxicity (DLT).The Recommended Dose (RD) is defined as one dose level below the MTD.
- Safety profile of drug combination [ Time Frame: from the first dose of investigational medication to 30 days after trial end. ] [ Designated as safety issue: Yes ]Safety will be assessed by physical examination, interim history, and laboratory assessments. Adverse events will be graded according to the NCI-CTCAE, version 3.0.
- Response Rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]For patients with measurable disease overall tumor response is performed according to RECIST criteria. For patients with non measurable disease (prostate and ovarian cancer) response can be assessed according to serum tumor markers (Rustin criteria for CA 125 and criteria for PSA response).
- PK parameters [ Time Frame: until 14 days post infusion ] [ Designated as safety issue: Yes ]PK parameters: terminal half life (T1/2), Total Body Clearance (ClTB), apparent volume of distribution (Vss), Cmax, Tmax, AUC0-48h, AUC0-inf
|Study Start Date:||October 2007|
|Estimated Study Completion Date:||December 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Experimental: RAD 001 in combination with CaelyxTM
RAD001 will be given p.o. at increasing doses (no intra-patient)and CaelyxTM will be administered i.v. at a fixed dose.
At each dose level 3 to 6 patients will be entered, according to toxicities observed; the first 3 patients can be treated simultaneously; subsequent patients can be treated after the first 3 have been observed for at least one cycle (4 weeks).
The dose escalation process will be discontinued once the MTD has been achieved and the RD will be evaluated in a subsequent expansion part of the study.
Drug: RAD 001 in combination with Caelyx
RAD001 (tablets; 2.5mg) is administered daily at 5, 7.5, 10 mg. CAELYXTM (vials; 50 mg/25mL)is administered i.v.every 4 weeks at 40mg/m2. One treatment cycle is 4 weeks.
mTOR inhibitors are a new class of targeted antitumor agents which showed interesting antitumor activity in a variety of solid tumors, including prostate, soft tissue sarcomas , ovarian, endometrial, kidney, and breast cancer. They also exert an antiangiogenic effect and are almost devoid of bone marrow toxicity as single agents which makes them suitable for combination with cytotoxic drugs.
Anthracyclines are among the most used and effective cytotoxic agents, and in solid tumors their indications include, among others, breast, ovary, endometrial, prostate cancer. Liposomal Doxorubicin (CaelyxTM) could be an adequate replacement of doxorubicin to avoid potential side effects such as cardiotoxicity, alopecia, GI toxicity.
Testing a combination regimen including mTOR inhibitors and anthracyclines in those tumors which are known to be sensitive to both compounds is of high clinical interest and worthwhile.
|Fondazione IRCSS Istituto Nazionale dei Tumori|
|Milan, Italy, 20133|
|Istituto Europeo di Oncologia|
|Milan, Italy, 20141|
|Istituto Oncologico della Svizzera Italiana|
|Bellinzona, Switzerland, 6500|
|Study Chair:||Cristiana Sessa, MD||Istituto Oncologico della Svizzera Italiana- Ospedale s.Giovanni - 6500 Bellinzona, Switzerland|