Sunitinib Malate Related Fatigue in Patients With Metastatic Kidney Cancer

Exploration of the Neuromuscular Mechanisms Associated With Sunitinib Related Fatigue

The purpose of this research study is to determine how sunitinib (sunitinib malate) causes fatigue. Patients will be asked to complete a brief questionnaire (survey) to rate their levels of fatigue every two weeks while they are participating in this research study. The questionnaire takes approximately 10-15 minutes to complete and is 9 questions. A series of physical measurements for fatigue will be performed before the first dose of sunitinib and again (4) weeks later to see if there are any changes in physical level of fatigues

Study Overview

• Status: Terminated
• Conditions: Fatigue; Stage IV Renal Cell Cancer; Recurrent Renal Cell Cancer
• Intervention / Treatment: Other: survey administration; Drug: sunitinib malate; Procedure: transcranial magnetic stimulation; Procedure: electromyography

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the mechanisms associated with sunitinib related fatigue by recording EMG signals during a submaximal elbow contraction, twitch force and TMS prior to and at the end of 4 weeks of sunitinib in metastatic RCC patients.

OUTLINE:

Patients receive sunitinib malate orally (PO) daily for 4 weeks. Patients undergo neuromuscular testing at baseline and on day 28 and complete fatigue assessment at baseline and on days 14 and 28.

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• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically proven renal cell cancer with metastases; pathology from either primary or metastatic tumor; no histologic subtype restriction
• Evidence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or evaluable disease
• Eastern Cooperative Oncology Group (ECOG) performance score 0 to 1
• Hemoglobin >= 9 gram/dL
• Common Terminology Criteria for Adverse Events (CTCAE) fatigue levels pre-treatment < 2
• Signed and dated informed consent

Exclusion Criteria:

• Greater than 2 previous systemic treatments for RCC
• Heart failure, New York Heart Association (NYHA) class 3 and 4
• Unstable angina (defined as ongoing use of nitrates or cardiac ischemia in the prior 6 months)
• Arrhythmia uncontrolled by medication
• Hypertension (> 160/90 mmHg) not controlled with medical management
• Brain metastases or previous cranial radiation, leptomeningeal cancer
• Surgery within 2 weeks of study entrance
• History of stroke, myasthenia gravis, multiple sclerosis, polyneuropathy
• Pregnancy or breast feeding
• Central-nervous system active medications, intake or withdrawal of which lowers seizure threshold (determination made in consultation with study's responsible treating physician)
• Any history of epilepsy, convulsion or seizure
• Medication-resistant epilepsy in a first-degree relative
• Cochlear implants or internal pulse generators or cardiac pacemakers or intracardiac lines
• Metallic implants in the vicinity of discharging coil in the head or cervical spine
• Unexplained fainting spells/syncope or multiple concussions
• History of severe head trauma (followed by loss of consciousness)
• Implanted brain or spinal cord electrodes/stimulation
• Medication infusion device
• Frequent/severe headaches or severe migraines
• Past or current medical history of diagnosed or undiagnosed tinnitus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supportive care (sunitinib malate, neuromuscular testing); Patients receive sunitinib malate PO daily for 4 weeks. Patients undergo neuromuscular testing at baseline and on day 28 and complete fatigue assessment at baseline and on days 14 and 28.	Other: survey administration; Ancillary studies; Drug: sunitinib malate; Given PO; Other Names: Sutent; SU11248; sunitinib; Procedure: transcranial magnetic stimulation; Undergo TMS; Other Names: TMS; Procedure: electromyography; Undergo EMG; Other Names: EMG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Muscular (Peripheral) Fatigue Maximal Twitch Force (MTF)	The MTF will be elicited by supramaximal-intensity electrical stimulation of the muscle before and after the sustained contraction (SC). If the muscle is fatigued at the end of the SC, the MTF will be reduced because the ability of muscle to generate force declines with fatigue. If the sunitinib treatment results in minimal muscular fatigue, the MTF will not have as much reduction in the 2nd as that in the 1st session.	Baseline and 28 days
Change in EMG Amplitude and Power Frequency	EMG amplitude will increase (for low-intensity SC) and mean power frequency (MPF) decrease with muscle fatigue. The EMG signals recorded during the SC, its amplitude and MPF will be analyzed to determine their changes at the end vs. beginning of the SC. If the sunitinib results in minimal muscular fatigue, the amount of EMG increase and MPF decrease will be reduced in the 2nd compared with those the 1st session.	Baseline and 28 days
Changes in Motor Evoked Potential (MEP) by TMS	TMS illustrates the changes in corticospinal excitability occurring in association with fatigue. Central muscle evoked response (MEP) will be elicited using transcranial magnetic stimulation (TMS) using single stimulus pulses applied to the scalp overlying the primary motor cortex.	Baseline and 28 days

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Brian Rini, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: November 30, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 4, 2012

Study Record Updates

• Last Update Posted (Actual): December 6, 2018
• Last Update Submitted That Met QC Criteria: November 14, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Fatigue; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: CASE8811; NCI-2012-00988 (Registry Identifier: CTRP (Clinical Trial Reporting Program))