Status:
UNKNOWN
Dose-finding Study of CAELYXTM and RAD001 in Patients With Advanced Solid Tumors
Lead Sponsor:
Southern Europe New Drug Organization
Collaborating Sponsors:
Novartis
Schering-Plough
Conditions:
Advanced Solid Tumors
Eligibility:
All Genders
Up to 75 years
Phase:
PHASE1
Brief Summary
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) an...
Detailed Description
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, ...
Eligibility Criteria
Inclusion
- Histological/cytological diagnosis of solid tumors types for which treatment with an anthracycline containing combination might be indicated.
- Documented progressive disease prior to entry in the study
- Though not a primary endpoint of this study when possible presence of measurable and/or evaluable disease according to modified RECIST criteria (histological/cytological confirmation of the neoplastic nature of a solitary lesion is not required in this dose finding study). For patients with no measurable disease (prostate and ovarian cancer) serum tumor marker (CA125 and PSA) is acceptable.
- Preferentially ≤ 2 prior chemotherapies for advanced disease
- An ECOG performance status of 0 or 1
- Serum cholesterol \<350 mg/dL and triglycerides \<400 mg/dL
- Adequate hematological, liver and renal function (hemoglobin ≥ 9g/dL, absolute neutrophil count \[ANC\] ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, bilirubin ≤ UNL; alkaline phosphatase ≤ 1.5 x UNL; AST, ALT ≤ UNL or 2.5 x UNL in case of liver metastases; albumin ≥ 2.5 g/dL; creatinine ≤ UNL.
- Male and female patients who are not surgically sterile or postmenopausal must agree to use reliable methods of birth control for the duration of the study until 30 days after the last dose of study drug
- Able to understand and give written informed consent
- Abdomen/Pelvis CT scans in the 4 weeks before planned treatment start
- HBV/HCV testing in the 2 weeks before treatment start in specific categories of patients with hepatitis B and C risk factors and in additional patients at the discretion of the investigators.
Exclusion
- Prior Caelyx TM
- Prior anthracycline therapy within last 12 months
- Patients with endometrial ca. who received both chemotherapy and radiotherapy as palliative treatment. Patients who received both chemotherapy and radiotherapy as adjuvant treatment would be accepted provided that treatment has been completed more than 2 years before inclusion; if treatments has been completed less than 2 years the inclusion will be accepted only after Study Chair's approval.
- Documented resistance to anthracycline therapy i.e progression whilst on therapy or within 6 months after the end of therapy having achieved a response or stable disease or after adjuvant therapy.
- Prior cumulative dose of \> 360 mg/m2 of doxorubicin or equivalent doxorubicin cardiotoxic dose and/or LVEF (echo or MUGA) \< 50%.
- Known metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, had a negative imaging study within 4 weeks of study entry, is clinically stable with respect to the tumor at the time of study entry, and is not receiving steroid therapy or taper
- Prior therapy with rapamycin, mTOR inhibitors or tacrolimus
- Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy, biological response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of RAD001; the interval is ≥ 2 weeks for signal transduction inhibitors with a half-life known to be \<24 hours, and is ≥ 6 weeks for nitrosourea or mitomycin. The following exceptions are allowed:
- hormonal therapy (e.g., Megace) for appetite stimulation
- nasal, ophthalmic, and topical glucocorticoid preparations
- a stable dose of corticosteroids for at least two weeks
- low dose maintenance steroid therapy for other conditions
- physiologic hormone replacement therapy (e.g., thyroid supplementation for thyroid deficiency or oral replacement glucocorticoid therapy for adrenal insufficiency)
- Pre-existing malabsorption syndrome, irritable bowel syndrome or other clinical situation which could affect oral absorption
- Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by NCI toxicity criteria and alopecia)
- Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ)
- Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
- Significant uncontrolled cardiovascular disease
- Active infection requiring systemic therapy
- Known HIV infection
- Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of RAD001. Patients having undergone recent placement of a central venous access port will be considered eligible if they have recovered
- Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluating the safety of the study drug
Key Trial Info
Start Date :
October 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2011
Estimated Enrollment :
54 Patients enrolled
Trial Details
Trial ID
NCT01148628
Start Date
October 1 2007
End Date
December 1 2011
Last Update
September 13 2011
Active Locations (3)
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1
Fondazione IRCSS Istituto Nazionale dei Tumori
Milan, Italy, 20133
2
Istituto Europeo di Oncologia
Milan, Italy, 20141
3
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland, 6500