RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder

Exclusion Criteria

• •Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.) with the exception of topical anti-neoplastic agents that are not being used to treat malignancy
• •Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study.
• •Prior treatment with any investigational drug within the preceding 4 weeks
• •Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• •Patients should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period
• •Other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin or adenocarcinoma of the prostate that has been treated.
• •Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• •symptomatic congestive heart failure of New York Heart Association Class III or IV
• •unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
• •Severely impaired lung function as defined by spirometry and diffusing capacity of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• •uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
• •active (acute or chronic) or uncontrolled severe infections including urinary tract infections
• •liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
• •A known history of HIV seropositivity
• •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small-bowel resection)
• •Patients with an active, bleeding diathesis
• •Female patients who are pregnant or breast feeding, Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of Everolimus.
• •Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. High effective contraception methods include combination of any two of the following (a+b or a+c or b+c):
• •Use of oral, injected or implanted hormonal methods of contraception or;
• •Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• •Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository;
• •Total abstinence or;
• •Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to registration. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
• •Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 8 weeks after the end of treatment.
• •Patients with a known hypersensitivity to Everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
• •History of noncompliance to medical regimens
• •Patients unwilling to or unable to comply with the protocol
• •Prior radiation to the pelvis for bladder cancer