Study of Temsirolimus, Topotecan, and Bortezomib

Inclusion Criteria:

1. Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months
2. Patients should be at least four weeks or 5 half lives from the last day of chemotherapy, and antibody or other biological therapy, whichever is shorter.
3. Patients should be at least four weeks from the last day of therapeutic radiation.
4. The Eastern Cooperative Oncology Group (ECOG) performance status \</= 2 or Karnofsky \>/= 60%.
5. Patients must have allowable organ and marrow function defined as: Absolute neutrophil count \>/= 1,000/mL, Platelets \>/=75,000/mL, Serum creatinine \</= 2 \* Upper Limit of Normal (ULN), Total bilirubin \</= 2 \* ULN, aminotransferase (ALT or SGPT) \</= 3 \* ULN, Fasting total cholesterol \<= 350 mg/dL and triglyceride level \<= 400 mg/dL.
6. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and will be advised to avoid pregnancy for 3 months after completion of therapy.
7. Ability to understand and the willingness to sign a written informed consent document.
8. Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies except for continuing on hormonal therapy in cases of prostate cancer.
9. Treatment on this study may begin within 24 hours after Phase 0 dose of temsirolimus.

Exclusion Criteria:

1. Patients with hemoptysis within 28 days prior to entering the study.
2. Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
3. Patients with clinically significant cardiovascular disease: • History of CVA within 6 months • Myocardial infarction or unstable angina within 6 months • Unstable angina pectoris
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
5. Pregnant or lactating women.
6. History of hypersensitivity to bortezomib or any component of the bortezomib formulation.
7. History of hypersensitivity to topotecan or any component of the topotecan formulation.
8. History of hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any component of the formulation.