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

Completed · Phase 1/Phase 2

Conditions studied: Gastrointestinal Cancer

In brief

Research has shown that anti-angiogenic agents can be effective therapies to treat cancer. Anti-angiogenic agents target the blood vessels required for tumors to grow. Vascular endothelial growth factor (VEGF) is one of the cell pathways used for this blood vessel growth. When the investigators interfere with the VEGF pathway, the investigators inhibit this blood vessel growth which is required by tumors. One of the study drugs being used, tivozanib (AV-951), selectively interferes with the VEGF pathway. The second study drug being used, everolimus (RAD001) interferes with the mTOR pathway. The mTOR pathway is another pathway involved in blood vessel and tumor cell growth. By combining these two drugs the investigators hope to slow or reverse tumor cell growth in patients whose tumors have become resistant to other therapies for their disease.

Key facts

Study ID

NCT01058655

Run by

Dana-Farber Cancer Institute

People needed

56

Starts

2010-02-01

Expected to finish

2015-04-01

Last updated by the study team

2017-04-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Massachusetts General Hospital — Boston, Massachusetts, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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