Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer

Korábbi kezelés

• 4.1 Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
• 4.8 Patients with prior abdominal surgery within 30 days prior to entering the study.
• 4.9 Medications with potent inducer or inhibitor of P450 3A4 should be avoided within 5 half lives of temsirolimus.

Más betegség

• 4.2 Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
• 4.3 Patients with clinically significant cardiovascular disease: History of CVA within 6 months Myocardial infarction or unstable angina within 6 months Unstable angina pectoris New York Heart Association Class > II
• 4.4 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
• 4.6 History of hypersensitivity to bevacizumab or murine products, temsirolimus or its metabolites, or any component of the formulation.
• 5.1 Hypersensitivity to carboplatin or any component of the formulation.
• 6.1 Hypersensitivity to paclitaxel or any component of the formulation.
• 7.1 History of hypersensitivity to sorafenib or any component of the formulation.

Egyéb

• Exclusion: (For all treatment arms)
• 4.5 Pregnant or lactating women.
• 4.7 Patients with hemorrhagic brain metastases.
• Exclusion: (For carboplatin treatment arm)
• Exclusion: (For paclitaxel treatment arm)
• Exclusion: (For sorafenib treatment arm)

• Inclusion: (For all treatment arms)
• 1.1 Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
• 1.2 Patients must have been off previous chemotherapy or radiotherapy for the three weeks prior to entering this study. Six weeks will be required if the patient has received therapy which is known to have delayed toxicity (mitomycin or a nitrosurea). Five half-lives will be required for biologic/targeted therapies with short (<24 hour) half-lives and pharmacodynamic effects. Patients may have received palliative radiation immediately before (or during) treatment provided radiation does not target the only measurable or evaluable disease.
• 1.3 Patients must have measurable or evaluable disease
• 1.4 ECOG performance status </= 2 (Karnofsky >/= 60%, Lansky >/= 50%).
• 1.5 Patients must have normal organ function defined as: creatinine </= 1.5 x ULN for children and </= 2.0 x ULN for adults; total bilirubin </= 2.0; ALT(SGPT)/AST (SGOT) </= 5 X ULN. In patients with significant liver disease and chronically elevated liver transaminases, ALT/AST may be elevated as high as 8 X ULN.
• 1.6 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, for the duration of study participation, and for 90 days after the last dose.
• 1.7 Ability to understand and the willingness to sign a written informed consent document.
• 1.8 Life expectancy of at least 3 months.
• 1.9 Patients may not be receiving any other experimental agents and/or any other concurrent anticancer agents or therapies except hormonal maintenance.
• Inclusion: (For carboplatin and paclitaxel arms)
• 2.1 Patients must have normal marrow function defined as: absolute neutrophil count >/= 1,500/mL; platelets >/= 100,000/mL.
• 2.2 Patient with neuropathies of CTC grade 1 or less.
• Inclusion: (For sorafenib arm)
• 3.1 Patients must have normal marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/= 75,000/mL.