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

NCT ID: NCT01164228

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-17
• Study Completion Date: 2021-11-03

Brief 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.

Detailed 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.

Conditions

Kidney Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (Sunitinib + Gemcitabine)

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. Each cycle was 42 days (6 weeks) and was to be repeated for a total of one year.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Given IV

Sunitinib

Intervention Type: DRUG

Given PO

Arm B (Sunitinib)

Patients receive oral sunitinib malate once daily on days 1-14 and 22-35. Each cycle was 42 days (6 weeks) and was to be repeated for a total of one year.

Group Type: EXPERIMENTAL

Sunitinib

Intervention Type: DRUG

Given PO

Interventions

Gemcitabine

Given IV

Intervention Type: DRUG

Sunitinib

Given PO

Intervention Type: DRUG

Other Intervention Names

2'-Deoxy-2'; 2'-difluorocytidine monohydrochloride; Gemzar; SU011248 L-Malate salt; SU010398; PHA-290940AD; Sutent; SU011248

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

ECOG-ACRIN Cancer Research Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Naomi S. Balzer-Haas, MD

Role: PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at Penn Medicine

Locations

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Stanford Cancer Center

Stanford, California, United States

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

St. Joseph Medical Center

Bloomington, Illinois, United States

Graham Hospital

Canton, Illinois, United States

Memorial Hospital

Carthage, Illinois, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Hematology and Oncology Associates

Chicago, Illinois, United States

Eureka Community Hospital

Eureka, Illinois, United States

Galesburg Clinic, PC

Galesburg, Illinois, United States

Kellogg Cancer Care Center

Highland Park, Illinois, United States

Provena St. Mary's Regional Cancer Center - Kankakee

Kankakee, Illinois, United States

North Shore Oncology and Hematology Associates, Limited - Libertyville

Libertyville, Illinois, United States

McDonough District Hospital

Macomb, Illinois, 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

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, United States

Proctor Hospital

Peoria, Illinois, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, United States

Methodist Medical Center of Illinois

Peoria, Illinois, United States

OSF St. Francis Medical Center

Peoria, Illinois, United States

Illinois Valley Community Hospital

Peru, Illinois, United States

Hematology Oncology Associates - Skokie

Skokie, Illinois, United States

Elkhart General Hospital

Elkhart, Indiana, United States

Howard Community Hospital

Kokomo, Indiana, United States

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, United States

Saint Joseph Regional Medical Center

Mishawaka, Indiana, United States

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

Memorial Hospital of South Bend

South Bend, Indiana, United States

McFarland Clinic, PC

Ames, Iowa, United States

McCreery Cancer Center at Ottumwa Regional

Ottumwa, Iowa, United States

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States

Mercy Medical Center - Sioux City

Sioux City, Iowa, United States

St. Luke's Regional Medical Center

Sioux City, Iowa, United States

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, 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

Cancer Center of Kansas - Fort Scott

Fort Scott, Kansas, United States

Cancer Center of Kansas-Independence

Independence, Kansas, United States

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, United States

Lawrence Memorial Hospital

Lawrence, Kansas, United States

Cancer Center of Kansas, PA - Liberal

Liberal, Kansas, United States

Cancer Center of Kansas, PA - McPherson

McPherson, Kansas, United States

Cancer Center of Kansas, PA - Newton

Newton, Kansas, United States

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, United States

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, United States

Cancer Center of Kansas, PA - Salina

Salina, Kansas, 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

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Union Hospital of Cecil County

Elkton, Maryland, United States

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Hurley Medical Center

Flint, Michigan, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Foote Memorial Hospital

Jackson, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Sparrow Regional Cancer Center

Lansing, Michigan, United States

St. Mary Mercy Hospital

Livonia, Michigan, United States

St. Joseph Mercy Oakland

Pontiac, Michigan, United States

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, 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

St. John Macomb Hospital

Warren, Michigan, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Beth Israel Medical Center - Petrie Division

New York, New York, United States

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

St. Rita's Medical Center

Lima, Ohio, United States

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States

Geisinger Hazleton Cancer Center

Hazleton, Pennsylvania, 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

Geisinger Medical Group - Scenery Park

State College, Pennsylvania, United States

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, United States

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States

Mary Babb Randolph Cancer Center at West Virginia University Hospitals

Morgantown, West Virginia, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Countries

United States

References

Carthon BC, Kim SE, McDermott DF, Dutcher JP, Puligandla M, Manola J, Pins M, Carducci MA, Plimack ER, Appleman LJ, MacVicar GR, Kohli M, Kuzel TM, DiPaola RS, Haas NB. Results From a Randomized Phase II Trial of Sunitinib and Gemcitabine or Sunitinib in Advanced Renal Cell Carcinoma with Sarcomatoid Features: ECOG-ACRIN E1808. Clin Genitourin Cancer. 2023 Oct;21(5):546-554. doi: 10.1016/j.clgc.2023.06.012. Epub 2023 Jul 3.

Reference Type: DERIVED

PMID: 37455214 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCT01164228

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2011-02055

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

E1808

Identifier Type: -

Identifier Source: org_study_id