Nab-Sirolimus in Combination With FOLFOX & BEV as 1st Line Therapy in Patients With Advanced or Metastatic Colorectal Cancer

Exclusion Criteria

• •1. History of severe and uncontrolled allergic reactions to bevacizumab
• •2. Prior treatment with FOLFOX or bevacizumab within the preceding 4 weeks
• •3. Patients currently receiving or have received anticancer therapies within 4 weeks of the start of study treatment (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• •4. 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 (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• •5. Chronic treatment with systemic steroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
• •6. Recent infection requiring systemic anti-infective treatment that was completed ≤14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection).
• •7. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including:
• •1. Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A patient with controlled and asymptomatic CNS metastases may participate in this study. As such, the patient must have completed any prior treatment for CNS metastases ≥28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.
• •2. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• •3. Pre-existing severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air (Note: spirometry and PFTs not required to be performed unless clinically indicated).
• •4. Uncontrolled diabetes as defined by fasting serum glucose \>1.5x ULN or by HbA1c \>8% despite adequate therapy.
• •5. Any active (acute or chronic) or uncontrolled infection/ disorders.
• •6. Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy. Note, controlled non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other adequately treated carcinoma-in-situ may be eligible, after documented discussion with the sponsor / medical monitor.
• •7. Known liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
• •8. Patients with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
• •9. A known history of HIV seropositivity.
• •10. Active Hepatitis B or Hepatitis C. Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
• •11. Patients with an active bleeding diathesis or on oral anti-vitamin K medication (except low dose Coumadin).
• •12. Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to receiving the first dose of ABI-009.