Combination Sunitinib and Gemcitabine in Sarcomatoid and/or Poor-risk Patients With Metastatic Renal Cell Carcinoma

Phase 2

Completed

Brief Summary: The purpose of this research study is to determine if the combination of sunitinib and gemcitabine is effective in treating patients with metastatic renal cell carcinoma. The safety of this combination will also be studied. Sunitinib is approved by the FDA for the treatment of renal cell carcinoma. However, some patients' cancers do not respond to treatment or stops responding after initially responding. 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 has suggested that combining gemcitabine with sunitinib may have some effectiveness in treating metastatic renal cell carcinoma.

Detailed Description: * Participants will receive study treatment as an outpatient. Study treatment will be given in 3-week cycles.

* Sunitinib will be taken orally once per day for the first two weeks (days 1-14) of each treatment cycle.

* Gemcitabine will be given intravenously at the study clinic on days 1 and 8 of each treatment cycle.

* Before receiving sunitinib and gemcitabine on day 1 of each cycle the following will be performed: physical exam, performance status assessment and blood work. Before receiving gemcitabine on day 8 the following will be performed: physical exam, performance status assessment and blood work. Every 3 cycles a CT scan will be performed to measure the tumor.

Recruitment & Eligibility

Inclusion Criteria

Histologically proven metastatic renal cell carcinoma with any sarcomatoid histology or poor-risk features as defined by having 3 or more of the following characteristics:
- PS > 1, high serum lactate dehydrogenase
- low hemoglobin
- high "corrected" serum calcium
- 2 or more sites of metastatic disease
- time from initial diagnosis to evidence of metastatic disease 12 months or less
Evidence of unidimensional measurable disease based on RECIST criteria, with at least 1 measurable lesion
Male or female, 18 years of age or older
ECOG performance status of 0-2
Patients with brain metastasis can only be included of they were treated 4 weeks or more prior to enrollment with whole brain radiation and the effects of treatment have resolved
Resolution of all acute toxic effects of prior therapy, radiotherapy or surgical procedure to NCI CTCAE version 3.0 grade of 1 or less
Laboratory values as outlined in the protocol
2 weeks or more must have elapsed from the time of major surgery or radiation therapy prior to the day of registration
No anticipated need for major surgical procedure during the course of the study

Exclusion Criteria

Prior treatment with sunitinib or gemcitabine
More than one prior systemic therapy of any kind for renal cell carcinoma
Uncontrolled high blood pressure
Any prior history of hypertensive crisis or hypertensive encephalopathy
Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or symptomatic congestive heart failure
Ejection fraction < 30%
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
NCT CTCAE grade 3 or higher hemorrhage within 4 weeks of starting treatment
Significant vascular disease
Current grade 3 or higher cardiac dysrhythmia or QT prolongation
Concurrent use of proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide
Pregnancy or breastfeeding or inadequate contraception
Evidence of bleeding diathesis or coagulopathy
Serious, non-healing wound, ulcer or bone fracture
Psychiatric illness/social situation that would limit compliance with study requirements
Previous diagnosis of concurrent malignancy requiring active systemic therapy

Arm && Interventions

Group	Intervention	Description
1	Sunitinib	Sunitinib and gemcitabine
1	Gemcitabine	Sunitinib and gemcitabine

Primary Outcome Measures

Name	Time	Method
To Determine the Overall Response Rate of Combination Therapy With Gemcitabine and Sunitinib in Sarcomatoid and/or Poor-risk mRCC Patients as First Line Therapy.	Until disease progression

Secondary Outcome Measures

Name	Time	Method

Locations (3): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center'
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Boston, Massachusetts, United States
Dana-Farber Cancer Institute
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Boston, Massachusetts, United States