Sunitinib Malate With or Without Gemcitabine Hydrochloride in Treating Patients With Advanced Kidney Cancer That Cannot Be Removed By Surgery

Kidney Cancer Clinical Trial

Official title:

A Randomized Phase II Trial of Sunitinib/Gemcitabine or Sunitinib in Advanced Renal Cell Carcinoma With Sarcomatoid Features

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01164228
• Other study ID #: E1808
• Secondary ID: NCI-2011-02055U1
• Status: Completed
• Phase: Phase 2
• Start date: September 17, 2010
• Est. completion date: November 3, 2021

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth or tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving sunitinib malate and gemcitabine hydrochloride together is more effective than sunitinib malate alone in treating patients with kidney cancer.

PURPOSE: This randomized phase II clinical trial is studying giving sunitinib malate together with or without gemcitabine hydrochloride to see how well they work in treating patients with advanced kidney cancer that cannot be removed by surgery.

Description:

OBJECTIVES:

Primary

• To evaluate the response rate to sunitinib malate with vs without gemcitabine hydrochloride in patients with advanced renal cell carcinoma with sarcomatoid features.

Secondary

• To evaluate progression-free survival of these patients.

• To evaluate overall survival of these patients.

• To describe the toxic effects of both sunitinib malate alone and in combination with gemcitabine hydrochloride in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (good risk [clear cell and < 20% sarcomatoid and performance status (PS) 0] vs intermediate risk [20-50% sarcomatoid and PS 0] vs poor risk [non-clear cell or > 50% sarcomatoid or PS 1 or non-clear cell]). Patients are randomized to 1 of 2 treatment arms.

• Arm A: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 22, and 29 and oral sunitinib malate once daily on days 1-14 and 22-35.

• Arm B: Patients receive oral sunitinib malate once daily on days 1-14 and 22-35.

In both arms, courses repeat every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

ACTUAL ACCRUAL: A total of 87 patients (47 in arm A and 40 in arm B) were accrued to this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: November 3, 2021
• Est. primary completion date: March 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed* renal cell carcinoma of any subtype containing any sarcomatoid features NOTE: *Patients must have a paraffin-embedded tumor specimen from the kidney or metastatic site available for central review and confirmation of tumor histology

• Measurable advanced disease that is not resectable by surgery

• Patients with resected or radiated brain metastases or those treated with stereotactic radiation therapy are eligible, provided they have been off steroids for at least 2 weeks

• More than 2 weeks since prior radiotherapy and recovered

• Previously irradiated lesions must not be the sole site of disease

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count (ANC) = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9.0 g/dL (transfusions allowed)

• Serum creatinine clearance = 30 mL/min

• serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) = 2.5 times upper limit of normal (ULN; = 5 times ULN in the presence of liver metastases)

• Total bilirubin = 1.5 times ULN

• Baseline corrected QT interval < 500 msec on EKG

• Able to swallow pills

• Negative pregnancy test

• Fertile patients must use effective contraception before and during study treatment

• More than 2 weeks since prior and no concurrent ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice

• Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been disease free for the time period considered appropriate to not interfere with the outcome of this study

Exclusion Criteria:

• Collecting duct or medullary carcinoma

• Prior systemic therapy for metastatic disease. One prior therapeutic regimen with a non-tyrosine kinase inhibitor, such as an mtor inhibitor is allowed. Patients who were randomized to placebo on an adjuvant study are eligible

• History of stroke within the past 6 months.

• Pregnant or nursing

• Clinically significant cardiovascular disease, defined as one of the following:

• Uncontrolled hypertension (blood pressure > 150/100 mm Hg at the time of enrollment); patients with hypertension and BP = 150/100 mm Hg on stable antihypertensive regimen are eligible

• History of myocardial infarction or unstable angina within the past 24 weeks

• New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris

• Peripheral vascular disease = grade II

• Ongoing ventricular cardiac dysrhythmias = grade 2 as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

• History of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation > 3 beats in a row)

• Ongoing atrial fibrillation

• Pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained at less than or within the normal range with medication

• Serious concurrent illness or active infection that would jeopardize the ability of the patient to receive study treatment

• Known HIV

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

Intervention

Drug:
• Gemcitabine
Given IV
• Sunitinib
Given PO

Locations

Country	Name	City	State
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	UAB Comprehensive Cancer Center	Birmingham	Alabama
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Eureka Community Hospital	Eureka	Illinois
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	St. Rita's Medical Center	Lima	Ohio
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	McDonough District Hospital	Macomb	Illinois
United States	Cancer Center of Kansas, PA - McPherson	McPherson	Kansas
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Stanford Cancer Center	Stanford	California
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	St. John Macomb Hospital	Warren	Michigan
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Response	Response is defined as either complete response (CR, disappearance of all lesions) or partial response (PR, at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters, or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits).	Assessed every 3 months for 2 years and every 6 months for year 3.
Secondary	Progression-free Survival	Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is defined as follows: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.; Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	Assessed every 3 months for 2 years and every 6 months for year 3.
Secondary	Overall Survival	Overall survival is defined as the time from randomization to death or date last known alive.	Assessed every 3 months for 2 years and every 6 months for year 3.