MDACC Study Summary ECOG2805

Study Summary
No. ECOG2805:.......Genitourinary......Christopher Wood......Urology

Study Summary Title



Study Summary Number:	ECOG2805

Study Title:	ASSURE: Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma

Physician

New Patient Referral



Name:	Christopher Wood	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Urology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-794-4397 Contact us about clinical trials

General Information



Disease Group:	Genitourinary	Supported By:	N/A

Phase of Study:	Phase III	Return Visit:	Patients will return to the clinic every 6 weeks while on treatment. Once treatment has been completed, or discontinued, patients will come back on an annual basis or as per standard of care for their condition.

Treatment Agents:	BAY 43-9006 SU011248	Home Care:	Blood pressure must be evaluated weekly during the first cycle. Measurements may be obtained outside of the treating physicians office, however, they must be documented on the patient's pill diary and phoned-in within 24 hours of the assessment.

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	Not applicable. The study treatment is given on an outpatient basis.


Description/ Intervention:	The goal of this clinical research study is to learn if either sunitinib or sorafenib can prevent recurrence of kidney cancer. Another goal of this study is to learn if sunitinib or sorafenib is more effective than placebo for treatment of kidney cancer. It is not known whether the benefits of taking either sunitinib or sorafenib will outweigh the risks.

Study Objectives / Outcomes

The primary objective of this study is to demonstrate an improvement in disease-free survival in locally advanced renal cell carcinoma patients randomly assigned to adjuvant Sunitinib (Arm A) or Sorafenib (Arm B) versus Placebo (Arm C) after radical or partial nephrectomy.

Secondary objectives are to:

Compare overall survival of patients randomized to each of the two regimens with placebo.
Further define the toxicity of prolonged administration of Sunitinib or Sorafenib in this patient population.
Prospectively collect tumor and biological specimens to assess their characteristics and associations:

- Novel approaches to assess angiogenesis markers in tissue, blood and urine as predictors of
disease-free survival and of therapeutic benefit
- The frequency of oncogene and tumor suppressor gene mutations as predictors of disease-free
survival and therapeutic benefit
- Tumor and genetic polymorphisms as predictors of disease-free survival and therapeutic benefit
- DNA methylation profiles as predictors of outcome and of therapeutic benefit
- The relationship of polymorphisms in drug metabolizing enzymes with steady state
concentrations of sorafenib and sunitinib in selected patients
- To study the effect of VEGF targeted therapy on circulating endothelial cells and circulating
endothelial progenitors

Evaluate the cardiac function in a subset of patients to determine if patients treated with sunitinib

or sorafenib experience clinically significant decreases in left ventricular ejection fraction.

Quality of Life Objectives:
To prospectively assess patient-reported fatigue in order to compare the magnitude and trajectory of fatigue
among RCC patients randomized to adjuvant Sunitinib (Arm A) or Sorafenib (Arm B) to placebo (Arm C).
To evaluate the PROMIS Fatigue-SF1, a newly developed state-of-thescience PROMIS measure for fatigue
and to calibrate the PROMIS Fatigue-SF1 with the established, validated FACIT-Fatigue scale.

Study Status Information



Study Activation / Registration Date:	07/26/2006

IRB Review and Approval Date:	07/26/2006

Study Type:	Phase Iii

Recruitment Status:	Closed

Projected Accrual:	1923

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) PRE-SURGERY: Patients must have primary-intact renal cell carcinoma, eligible for nephrectomy with curative intent (only applies to patients registered pre-surgery)

2) PRE-SURGERY: Tumors >/= 4 cm AND/OR macroscopic fully resectable nodes AND/OR surgically resectable renal vein thrombus AND/OR surgically resectable inferior vena cava thrombus by radiologic criteria to be clinically >/= pT1bNany (resectable) M0 disease.

3) PRE-SURGERY: Multifocal ipsilateral renal cell carcinoma is allowed provided fully resectable and does not exceed inclusion criteria.

4) PRE-SURGERY: Patients must have no history of distant metastases

5) PRE-SURGERY: No prior anti-cancer therapy for renal cell carcinoma is permitted in either the adjuvant or neoadjuvant setting. This includes metastectomy for renal cell carcinoma, or radiation therapy to the renal bed

6) PRE-SURGERY: Patients must be at least 18 years of age

7) PRE-SURGERY: Patients must have no other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast. Patients with other malignancies are eligible if they have been continuously disease-free for >/= 5 years prior to the time of randomization

8) PRE-SURGERY: Patients must have QTc interval < 500 msec on baseline EKG.

9) PRE-SURGERY: If female, patient must not be pregnant or breastfeeding. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to preregistration to rule out pregnancy. If pre-registration occurs prior to surgery, the blood or urine study must be repeated within 2 weeks prior to randomization to rule out pregnancy.

10) PRE-SURGERY: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

11) POST-SURGERY: ECOG performance status 0-1

12) POST-SURGERY: POST-SURGERY: Patients must have histologically or cytologically confirmed renal cell carcinoma. Using 2002 (AJCC 6th edition) TNM staging. patients must be one of the Following: a) pT1b G3-4 N0(or pNX where clinically N0) M0 b) pT2 G(any) N0 (or pNX where clinically N0) M0 c) pT3 G(any) N0(or pNX where clinically N0) M0 d) pT4 G(any) N0(or pNX where clinically N0) M0 or e) T(any) G(any) N+(fully resected) M0. Patients with microvascular invasion of the renal vein of any grade or stage are also eligible.

13) POST-SURGERY: Patients must have paraffin-embedded tumor specimen available for central core review of tumor histology and other correlative studies.

14) POST-SURGERY: Patient must have no evidence of residual or metastatic renal cell cancer as documented on CT scan of chest abdomen and pelvis with oral and IV contrast (or MRI scan of the abdomen and pelvis with gadolinium and a CT of the chest with or without IV contrast) within 4 weeks of randomization. Changes on CT scan that are felt to be postsurgical must be documented.

15) POST-SURGERY: Patients must have the following baseline laboratory values within 4 weeks of randomization: Absolute Granulocyte Count (AGC) >/= 1,500/mm^3, Platelet Count >/= 100,000/mm^3, Serum creatinine </= 2.0 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >/= 30ml/min, Total Bilirubin </= 1.5 x ULN, SGOT and SGPT </= 2.5 x ULN

16) POST-SURGERY: Patients must begin protocol treatment 4-12 weeks post surgery. As a result, IT IS STRONGLY RECOMMENDED that the patient is registered at least 7-10 working days prior to the 12-week post-operative limit to ensure adequate time is available for shipment and receipt of the patient's assigned treatment from PMB. Patients must have recovered from any surgical related complications.

17) POST-SURGERY: Patients must be able to swallow pills.

18) POST-SUREGERY: Patients must have an absolute baseline left ventricular ejection fraction of >/= 50% by MUGA scan within 4 weeks prior to randomization.

Exclusion Criteria:

1) PRE-SURGERY: Patients with serious intercurrent illness including, but not limited to, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease or psychiatric illness/social situations that would limit compliance with study requirements.

2) PRE-SURGERY: Patients with any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.

3) PRE-SURGERY: Patients with ongoing ventricular cardiac dysrhythmias of NCI CTCAE Version 3.0 grade >/=2. Patients with a history of serious ventricular arrhythmia (VT or VF>/=3 beats in a row) are also excluded. Additionally, patients with ongoing atrial fibrillation are not eligible.

4) PRE-SURGERY: Patients with hypertension that cannot be controlled by medications (> diastolic blood pressure 100 mm Hg despite optimal medical therapy).

5) PRE-SURGERY: Patient with pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained in the normal range with medication.

6) PRE-SURGERY: Patients with known HIV are excluded due to possible effects on immune system by these agents. The potential impact of pharmacokinetic interactions of retroviral therapy with sunitinib or sorafenib is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.

7) POST-SURGERY: Patients with collecting duct carcinomas or medullary carcinomas.

8) POST-SURGERY: Patients taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), St John's Wort, ketoconazole, dexamethasone, the dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide or flecainide), haloperidol, risperidone, rifampin, grapefruit or grapefuit juice within two weeks of randomization and during the course of therapy. Topical and inhaled steroids are permitted.

9) POST-SURGERY: Patients receiving any other investigational anti-cancer agents during the period on study.

10) POST-SURGERY: Patients with an ongoing or active infection requiring parental antibiotics.

Links

Registration Number: NCT00326898
Study Information on Clinical Trials Registry (clinicaltrials.gov)