Ethyl Icosapentate and Physical Activity in Treating Fatigue in Patients With Advanced Cancer
Condition: Advanced Malignant Neoplasm; Fatigue
MeSH terms: Neoplasms; Fatigue
Intervention: Ethyl Icosapentate; Exercise Intervention; Exercise Intervention; Laboratory Biomarker Analysis; Placebo; Quality-of-Life Assessment; Questionnaire Administration
Intervention description: Given by mouth 2 gm orally daily plus physical activity; Complete resistance exercises and undergo walking program; Meet with exercise specialist and complete stretching exercises; Correlative studies; Given PO; Ancillary studies; Ancillary studies
Intervention MeSH terms: Eicosapentaenoic acid ethyl ester
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well ethyl icosapentate and physical activity work
      in treating fatigue in patients with cancer that has spread from where it started to other
      places in the body. Ethyl icosapentate and physical activity may provide more robust and
      clinically effective improvement of cancer related fatigue, which may facilitate patients
      continuing cancer therapy since it would be tolerated and effective in controlling disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of advanced cancer

          -  Patients should describe fatigue as being present for a minimum of 2 weeks

          -  Patients should rate the severity of fatigue as 4/10 in a 0-10 ESAS scale, where 0 =
             no fatigue, 10 = worse fatigue possible

          -  If patients are on opioids for the treatment of cancer pain, they must have had no
             major dose change (> 25%) for at least 48 hours prior to study entry; change in opioid
             dose after study entry is allowed

          -  Presence of relatively intact cognition defined by normal memorial delirium assessment
             scale (< 7/30); sign written informed consent

          -  Patient willing to keep a daily diary, engage in telephone follow up with a nurse

          -  Patient must have telephone access to be contacted by the research nurse

          -  Hemoglobin of >= 10 g/dl within 2 weeks of enrollment; if the patient has not had
             blood drawn for a hemoglobin level in the past two weeks, one will be done to
             determine the eligibility

          -  Patients should have a Zubrod =< 1

          -  Life expectancy of >= 4 months

          -  Subjects must be able to understand and be willing to sign the written informed
             consent form; a signed informed consent form must be appropriately obtained prior to
             the conduct of any trial-specific procedure

          -  Total bilirubin =< 1.5 x the upper limits of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) =< 2.5 x ULN (=<
             5 x ULN for subjects with liver involvement of their cancer)

          -  Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for subjects with liver
             involvement of their cancer)

          -  Serum creatinine =< 1.5 x the ULN

          -  International normalized ratio (INR)/ partial thromboplastin time (PTT) =< 1.5 x ULN

          -  Platelet count > 100000/mm^3

          -  Hemoglobin (Hb) > 9 g/dL

          -  Absolute neutrophil count (ANC) 1500/mm^3

          -  Blood transfusion to meet the inclusion criteria will not be allowed

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of study drug; post-menopausal women (defined as no
             menses for at least 1 year) and surgically sterilized women are not required to
             undergo a pregnancy test; the definition of adequate contraception will be based on
             the judgment of the investigator

          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the informed consent form (ICF) until at
             least 2 months after the last dose of study drug; the definition of adequate
             contraception will be based on the judgment of the principal investigator or a
             designated associate

          -  Subject must be able to swallow and retain oral medication

          -  Patients on pain medications (non-opioids), including nonsteroidal anti-inflammatory
             drugs (NSAIDS) and acetaminophen, may be enrolled as long as they have been using it
             chronically, at least more than 2 weeks

        Exclusion Criteria:

          -  Major contraindication to fish oil i.e. hypersensitivity to fish/oil or physical
             activity

          -  Currently on fish oil or has been on fish oil within the last 10 days

          -  Inability to complete the baseline assessment forms or to understand the
             recommendations for participation in the study

          -  Pregnant or lactating women; childbearing age women are not on birth control

          -  Reports a fall in the past 30 days

          -  Patient reported regular participation in moderate- or vigorous-intensity physical
             activity for at >= 30 minutes at least 5 times a week and strength training for >= 2
             days/week

          -  Signs of third spacing as determined by the treating physician (e.g., pedal edema,
             pleural effusion, ascites)

          -  Previous assignment to treatment during this study; subjects permanently withdrawn
             from study participation will not be allowed to re-enter study

          -  Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm
             Hg [National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events
             (CTCAE) version (v)4.0] on repeated measurement) despite optimal medical management

          -  Active or clinically significant cardiac disease including: a. congestive heart
             failure-New York Heart Association (NYHA) > class II; b. active coronary artery
             disease; c. cardiac arrhythmias requiring anti-arrhythmic therapy other than beta
             blockers or digoxin; d. unstable angina (anginal symptoms at rest), new-onset angina
             within 3 months before randomization, or myocardial infarction within 6 months before
             randomization

          -  Evidence or history of bleeding diathesis or coagulopathy

          -  Any hemorrhage or bleeding event >= NCI CTCAE grade 3 within 4 weeks prior to start of
             study medication

          -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
             accident (including transient ischemic attacks) deep vein thrombosis or pulmonary
             embolism within 6 months of start of study treatment within 6 months of informed
             consent

          -  Patients with any previously untreated or concurrent cancer that is distinct in
             primary site or histology except cervical cancer in-situ, treated ductal carcinoma in
             situ of the breast, curatively treated nonmelanoma skin carcinoma, noninvasive
             aerodigestive neoplasms, or superficial bladder tumor; subjects surviving a cancer
             that was curatively treated and without evidence of disease for more than 3 years
             before registration are allowed; all cancer treatments must be completed at least 3
             years prior to registration

          -  Patients with phaeochromocytoma

          -  Known history of human immunodeficiency virus (HIV) infection or current chronic or
             active hepatitis B or C infection requiring treatment with antiviral therapy

          -  Ongoing infection > grade 2 NCI-CTCAE v4.0

          -  Symptomatic metastatic brain or meningeal tumors

          -  Presence of a non-healing wound, non-healing ulcer, or bone fracture

          -  Major surgical procedure or significant traumatic injury within 28 days before start
             of study medication

          -  Renal failure requiring hemo-or peritoneal dialysis

          -  Dehydration grade > 1 NCI-CTCAE v4.0

          -  Patients with seizure disorder requiring medication

          -  History of persistent proteinuria >= grade 3 NCI-CTCAE v4.0

          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed
             consent

          -  Pleural effusion or ascites that causes respiratory compromise (>= NCI-CTCAE version
             4.0 grade 2 dyspnea); a) history of organ allograft (including corneal transplant); b)
             known or suspected allergy or hypersensitivity to any of the study drugs, study drug
             classes, or excipients of the formulations given during the course of this trial; c)
             any malabsorption condition; d) any condition which, in the investigator's opinion,
             makes the subject unsuitable for trial participation; e) substance abuse, medical,
             psychological or social conditions that may interfere with the subject's participation
             in the study or evaluation of the study results

          -  Concurrent use of another investigational drug or device therapy (i.e., outside of
             study treatment) during, or within 4 weeks of trial entry (signing of the informed
             consent form)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             before start of study medication

          -  Therapeutic anticoagulation with vitamin-K antagonists (e.g., warfarin) or with
             heparins and heparinoids; however, prophylactic anticoagulation as described below is
             allowed: 1. low dose warfarin (1 mg orally, once daily) with prothrombin time [PT]-INR
             =< 1.5 x ULN is permitted; we will monitor the PT/INR weekly for patients on warfarin
             and liver function test every 2 weeks (total bilirubin, and AST (serum glutamic
             oxaloacetic transaminase [SGOT]) and ALT (serum glutamic pyruvic transaminase [SGPT])
             if hepatic metastases are present or if patients are on potentially hepatoxic agents
             such as acetaminophen or statins; 2. low dose aspirin (=< 100 mg daily); and 3.
             prophylactic doses of heparin

          -  Use of any herbal remedy (e.g. St. John's wort [Hypericum perforatum])

          -  Use of dexamethasone for cancer related fatigue