Tivozanib + Gemcitabine in Metastatic RCC

This research study is a PHase II clinical trial, which tests the safety and effectiveness of an investigational combination of drugs to learn whether the combination of drugs works in treating a specific cancer. "Investigational" means that the combination of drugs is being studied. It also means that the FDA has not yet approved these drugs or combination of drugs for use in participants, including people with your type of cancer. Tivozanib is an anti-angiogenesis medicine that fights cancer by cutting off a tumor's blood supply so that it does not get the blood and nutrients it needs to grow. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to slow the growth of cancer cells. Gemcitabine is a chemotherapy drug that is approved by the FDA for the treatment of pancreatic cancer and several other cancers. It is not approved for the treatment of renal cell carcinoma. Previous research suggests combining gemcitabine with tivozanib may have some effectiveness in treating metastatic renal cell carcinoma. The purpose of this research study is to determine the effectiveness of tivozanib as a treatment for renal cell carcinoma. The purpose of this research study is to also determine if the combination of tivozanib and gemcitabine is effective in treating your type of cancer if your cancer becomes unresponsive or gets worse with tivozanib as treatment alone. The safety of the combination of tivozanib and gemcitabine will also wbe studied. Another goal of this research study is to learn more about how tivozanib alone and the combination of tivozanib and gemcitabine may work to treat renal cell carcinoma. During the research study we will perform blood tests to measure the level of substances in the blood such as proteins (biomarkers) that may predict who will respond to treatment with tivozanib and gemcitabine.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Histologically confirmed renal cell carcinoma that is metastatic
* Failed at least one prior VEGF-targeted therapy
* Prior immunotherapy and mTOR inhibitors are allowed
* Evidence of unidimensionally measurable disease based on RECIST 1.1 criteria, with at least 1 measurable lesion
* Willing to use adequate contraceptive measures while on study and for 30 days after the lst dose of study drug
* For Segment 2, must have evidence of progressive disease
* For Segment 2, amenable to start Gemcitabine chemotherapy within 6 weeks of progression on Tivozanib
* For Segment 2, willing to undergo pre/post therapy biopsy of a metastatic lesion if safe and amenable

Exclusion Criteria:

* Prior gemcitabine or tivozanib
* Anticipated need for major surgical procedure during the course of the study
* Pregnant or breastfeeding
* Known prior history of hypertensive crisis or hypertensive encephalopathy
* Primary central nervous system malignancies or leptomeningeal metastases
* Significant cardiac disease
* Subjects on warfarin
* Uncontrolled intercurrent illness
* Evidence of bleeding diathesis or known coagulopathy
* Serious, non-healing wound, ulcer or bone fracture
* Psychiatric illness/social situation that would limit compliance with study requirements
* Previous or concurrent malignancy requiring active systemic therapy, \< 4 years
* Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of tivozanib, major resection of the stomach or small bowel, or gastric bypass procedure
* Ongoing use of strong CYP3A4 inducers