RAD001 and AV-951 in Patients With Refractory, Metastatic Colorectal Cancer

For the Phase I component: Inclusion Criteria: * 18 years of age or older * Histologic confirmation of a gastrointestinal malignancy, limited to cancer of the esophagus, stomach, small bowel, liver, biliary tract, gallbladder, pancreas, large bowel, appendix, rectum and anus. * Locally advanced or metastatic disease * Disease that: a) has recurred or progressed following standard therapy, b) for which no standard therapy currently exists, or c) for which the subject is not a candidate for or unwilling to undergo standard therapy. There is no limit to the number of prior regimens received by the patient. * ECOG Performance Status of 0, 1 or 2 * Life expectancy of at least 12 weeks * Adequate organ function as outlined in the protocol * At least 4 weeks is required from : a) previous regimen of chemotherapy, b) immunotherapy or biological therapy, c) other investigational agents, and d) radiotherapy. * At least 4 weeks is required from treatment of bevacizumab * At least 4 weeks is required from prior systemic hormonal therapy or treatment with strong CYP3A4 inducers or inhibitors * If female and of child bearing potential, documentation of negative pregnancy test prior to enrollment. Exclusion Criteria: * Prior therapy with inhibitors of mTOR or VEGFR (prior treatment with bevacizumab is allowed). * Clinically apparent CNS metastases or carcinomatous meningitis * Clinically significant cardiovascular disease * Major surgery within 4 weeks of the start of study treatment or patients who have not recovered from the side effects of any major surgery. * Active bleeding diathesis or history of Grade 2 or greater clinically significant bleeding within 3 months of enrollment * Active infection requiring antibiotics * Participants with a known positive history of chronic Hepatitis B viral infection or known positive HBV-DNA test are excluded. * History of interstitial pneumonitis or severely impaired lung function defined as 88% or less O2 saturation at rest in room air * Immunocompromise or chronic use of immunosuppressant medications * Uncontrolled serious medical or psychiatric illness * Subjects with non-healing wounds, active peptic ulcers, or unhealed bone fractures * Significant proteinuria, defined as urine dipstick protein of 3+ or greater * Concurrent malignancy (other than non-melanoma skin cancer) diagnosed within the past 3 years or any currently active malignancy * Elevated fasting levels of the following: serum cholesterol, serum triglycerides, and serum glucose * Patients who are pregnant or lactating * Malabsorption, uncontrolled vomiting or diarrhea, or any disease significantly affecting gastrointestinal function that could interfere with absorption of study drugs * Inability to swallow pills For the phase II component, only patients with metastatic colorectal cancer will be enrolled. For the Phase II component: Inclusion Criteria (Phase II): * 18 years of age or older * Histologic confirmation of colorectal cancer * Stage IV disease * At least one site of disease measurable by RECIST criteria * Receipt of or intolerance to a fluoropyrimidine (fluorouracil or capecitabine), irinotecan, oxaliplatin, bevacizumab, and a monoclonal antibody to epidermal growth factor receptor (cetuximab or panitumumab). If a patient's tumor was K-RAS mutation positive, then previous treatment with cetuximab or panitumumab is not required. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * Life expectancy of at least 12 weeks * Adequate organ function as outlined in the protocol * At least 3 weeks is required from: (a) previous regimen of chemotherapy, (b)immunotherapy or biological therapy, (c) other investigational agents, and (d) radiotherapy. Of note, concomitant radiotherapy is NOT allowed, while a patient is on protocol. * At least 3 weeks is required from prior treatment with bevacizumab * At least 3 weeks is required since prior systemic hormonal therapy or treatment with strong CYP3A4 inducers or inhibitors. * Negative pregnancy test for women of child bearing potential Exclusion Criteria (Phase II): * Prior therapy with inhibitors of mTOR or VEGFR (prior treatment with bevacizumab is allowed) * Clinically apparent CNS metastases or carcinomatous meningitis, as determined by physical examination and imaging studies * Clinically significant cardiovascular disease, defined as follows: (A)Symptomatic congestive heart failure, (B)Symptomatic coronary artery disease or myocardial infarction within 3 months of enrollment, (C)Cardiac arrhythmias not controlled with medication, (D)Deep venous thrombosis or pulmonary embolus within the last 6 months, (E) Cerebrovascular accident within the last 12 months, (F)Poorly controlled hypertension, defined as systolic pressure \> 150 mmHg or diastolic pressure \> 100 mmHg documented on 2 consecutive measurements taken at least 24 hours apart, (G)Symptomatic peripheral vascular disease, defined as claudication on walking ≤ 1 block * Major surgery within 4 weeks of the start of study treatment or patients who have not recovered from the side effects of any major surgery. Major surgery defined as those surgeries that require general anesthesia * Active bleeding diathesis or history of grade 2 or higher clinically significant bleeding (hemoptysis, hematemesis, hematochezia, or melena) within 3 months of enrollment * Active infection requiring antibiotics * Participants with a known positive history of chronic Hepatitis B viral infection or known positive HBV-DNA test are excluded. * History of interstitial pneumonitis or severely impaired lung function defined as less than or equal to 88% O2 saturation at rest in room air. * Immunocompromise or chronic use of immunosuppressant medications (prednisone ≤ 10 mg daily or the equivalent of a comparable steroid is allowed, if deemed necessary by a study investigator) * Uncontrolled serious medical or psychiatric illness * Subjects with non-healing wounds, active peptic ulcers, or unhealed bone fractures * Significant proteinuria, defined as urine dipstick protein 3+ or greater * Concurrent malignancy (other than non-melanoma skin cancer) diagnosed within the past 3 years or any currently active malignancy. * Elevated fasting levels of the following: serum cholesterol, serum triglycerides, and serum glucose. * Patients who are pregnant or lactating * Malabsorption, uncontrolled vomiting or diarrhea, or any disease significantly affecting gastrointestinal function that could interfere with absorption of study drugs * Inability to swallow pills