American Ginseng in Treating Patients With Fatigue Caused by Cancer

Study Overview
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Brief Summary
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RATIONALE: American ginseng may reduce fatigue in patients with cancer. It is not yet known whether American ginseng is more effective than a placebo in treating cancer-related fatigue. PURPOSE: This randomized phase III trial is studying American ginseng to see how well it works in treating patients with fatigue caused by cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate the efficacy of American ginseng (Panax quinquefolius) as therapy for cancer-related fatigue as measured by the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Secondary To evaluate toxicities and tolerability of American ginseng when used for cancer-related fatigue. To examine stress as a mediating variable on the effects of American ginseng on cancer-related fatigue. To explore the impact of American ginseng on various dimensions of fatigue as measured by the other subscales of the MFSI-SF, functional interference as measured by the Brief Fatigue Inventory (BFI), stress as measured by the Perceived Stress Scale, and well being as measured by the Profile of Mood States (POMS), as well as the single measure of fatigue. To determine clinically significant changes in fatigue scores using the global impression of change. To evaluate whether there are differences in the efficacy of American ginseng for fatigue based on minority populations. Tertiary To describe cortisol and cytokine values in fatigued cancer survivors and to evaluate the relationship of cortisol and cytokines to fatigue severity as well as to patterns of alterations previously documented in fatigued breast cancer survivors. To evaluate whether Wisconsin Ginseng impacts the expression of cortisol and cytokine in fatigued cancer survivors. To evaluate the role of cortisol and cytokine changes as the mechanism by which Wisconsin Ginseng can ameliorate cancer related fatigue. To evaluate the relationships between cytokine and cortisol levels with secondary outcomes such as mood and stress. OUTLINE: This is a multicenter study. Patients are stratified according to baseline fatigue score (4-7 vs 8-10), disease status of current cancer (initial diagnosis vs recurrent disease), current treatment (chemotherapy, radiation, endocrine therapy [i.e., tamoxifen or aromatase inhibitors], or other targeted therapy) ( yes vs no), duration of all prior cancer treatment in patient's lifetime (none vs ≤ 180 days vs > 180 days), and current tumor type (hematologic vs solid tumor malignancy). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral American ginseng twice daily for 14 days. Treatment repeats every 2 weeks for 4 courses until disease progression or unacceptable toxicity. Arm II: Patients receive oral placebo twice daily for 14 days. Treatment repeats every 2 weeks for 4 courses. Patients are instructed to complete the Ginseng Symptom Experience Diary and the Linear Analogue Scale weekly. Patients also complete the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), the Profile of Mood States (POMS), and the Brief Fatigue Inventory (BFI) questionnaires at baseline and periodically during study therapy. Patients who are not actively receiving chemotherapy or radiation therapy undergo blood and saliva sample collection at baseline and periodically during study therapy for correlative studies.

Official Title
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The Use of American Ginseng (Panax Quinquefolius) to Improve Cancer-Related Fatigue: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

Conditions
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Chronic Myeloproliferative Disorders, Fatigue, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: American ginseng
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Required characteristics ≥ 18 years of age Men or women with a history of cancer-related fatigue as defined by an average score ≥ 4 over the past 30 days on the numeric analogue scale (1 - 10) The presence of fatigue ≥ 1 month prior to randomization ECOG performance score 0, 1, or 2 Histologic or cytologic proven cancer other than brain cancer or CNS lymphoma, undergoing curative intent therapy (including anti-hormonal therapies such as tamoxifen or leuprolide) or those having completed curative intent therapy who were diagnosed within the past 2 years Note: If a patient is receiving treatment for their disease such as chemotherapy, targeted therapies, immunotherapy or radiation therapy then, the patient must have completed ≥ 1 cycle of chemotherapy, targeted therapy, or ≥ 1 week of radiation treatment. Laboratory values obtained prior to randomization: Hgb ≥ 11 (must be obtained ≤ 30 days; patients must not be transfused ≤ 30 days to meet this criterion) Creatinine ≤ 1.2 x UNL (must be obtained ≤ 180 days prior to randomization) AST (SGOT) or ALT (SGPT) ≤ 1.5 x UNL (must be obtained ≤ 180 days prior to randomization) Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only Ability to complete patient questionnaires alone or with assistance Controlled: Pain (≤ 4 on Linear Analogue Scale) Insomnia (≤ 4 on Linear Analogue Scale) Willingness to provide blood/saliva samples for correlative studies. Note: These samples are only required for those not receiving active treatment for their disease. Active treatment is defined as chemotherapy, radiation therapy, or immunotherapy, not anti-hormone therapy such as tamoxifen, aromatase inhibitors or leuprolide. Contraindications Hypersensitivity to ginseng Prior use of ginseng capsules for fatigue in the past year Note: Prior use of teas or drinks containing ginseng is allowed, however, patients will be asked to avoid these beverages while on the study. Uncontrolled hypertension on more than one occasion (diastolic blood pressure > 100, systolic > 160) measured ≤ 90 days prior to randomization Currently using any other pharmacologic agents or nonpharmacologic interventions to specifically treat fatigue including psychostimulants, antidepressants, acupuncture, etc. Note: Antidepressants used to treat items other than fatigue (such as hot flashes) are allowed if the patient has been on a stable dose for ≥ 1 month and plans to continue for ≥ 1 month. Erythropoietin agents to treat anemia are allowed. Exercise is allowed. Known brain metastasis or primary CNS malignancy Chronic systemic steroid use (including CHOP therapy or as part of any regular cancer treatment, however, steroids used as prophylaxis for nausea and vomiting are allowed) to prevent rash with Alimta, low dose dexamethasone will be allowed. Diabetes Type I or II (defined by being on oral hypoglycemics or insulin). Psychiatric disorder such as severe depression, manic depressive disorder, obsessive compulsive disorder or schizophrenia. (Defined per medical history). ≤ 4 weeks from major surgery to randomization, including any procedure that requires general anesthetic Any of the following: Pregnant women Nursing women Women of childbearing potential who are unwilling to employ adequate contraception Pain requiring opioid pain medication, however, over the counter analgesics such as Tylenol or ibuprofen are allowed. Use of full dose of anticoagulant therapy (Exception: 1 mg/day of Coumadin for preventing catheter clots is allowed). Use of MAO inhibitors. Planning to start or complete any type of cancer therapy during the 8 week, double blind, course of the study, once randomized on the study. Note: If not currently getting treatment, no chemotherapy agents ≤ 21 days prior to randomization. Combination treatment regimens that have components ending at different times are allowed, as long as any part of the initially started treatment continues through the double blind portion of the study. Malnutrition, active infection, significant pulmonary disease and cardiovascular disease as determined by the physician, as they could impact fatigue. Use of any over the counter herbal/dietary supplement marketed for fatigue or energy (for example, products containing any type of ginseng, rhodiola rosea, high doses of caffeine, guarana, or anything called an adaptogen). Uncontrolled nausea or vomiting or any symptom that would prevent the ability to comply with daily oral ginseng/placebo treatment. Uncontrolled thyroid disorder. Currently receiving single agent on blinded placebo controlled treatment trials.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral American ginseng twice daily for 14 days. Treatment repeats every 2 weeks for 4 courses. | Drug: American ginseng<br>* Given orally<br>|
| Placebo Comparator: Arm II<br>Patients receive oral placebo twice daily for 14 days. Treatment repeats every 2 weeks for 4 courses. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 4 in the General Subscale of the MFSI-SF | Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) general subscale is a six-item subscale to measure the subjective experience of fatigue. The items include feeling pooped, worn out, fatigued, sluggish, run down and tired. Answers are on a 5-point scale, ranging from 0 (not at all) to 4 (extremely). The subscale scores were the sum of all six items. The scores were converted to a 100-point scale, with higher numbers indicating less fatigue. Change from baseline to week 4 was calculated by subtracting the baseline scores from the scores at week 4. | Baseline and week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Related Grade 2 to 3 Adverse Events >=1% Incidence | Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death. | Week 1 to Week 8 | 
| Change From Baseline to Week 4 in the Impact on Physical, Mental, and Emotional States and Vigor as Measured by Other Subscales of the MFSI-SF | Each MFSI-SF subscale consist of 6 items on a 5-point scale, ranging from 0 (not at all) to 4 (extremely). The subscale scores were the sum of all six items. The scores were then converted to a 100-point scale, with higher numbers indicating less fatigue. Change from baseline to week 4 was calculated by subtracting the baseline scores from the scores at week 4. | Baseline and Week 4 | 
| Change From Baseline to Week 4 Fatigue as Measured by the BFI and Linear Analogue Scale of Fatigue | Brief Fatigue Inventory (BFI) consist of 3 items that assess the severity of fatigue and 6 items that assess the impact of fatigue on daily functioning in a 10-points scale with 0 as no fatigue or does not interfere with daily functioning and 10 as bad fatigue or completely interferes. The scores for the six items were summed up to form a total interference score. The linear analogue scale of fatigue was a 10-points scale with 0 as no fatigue and 10 as bad fatigue. All scores were then transformed into 0 to 100 scale, with 100 as less fatigue/less interference. Change from baseline to week 4 was calculated by subtracting the baseline scores from the scores at week 4. | Baseline and Week 4 | 
| Change From Baseline to Week 4 Vigor/Activity and Fatigue-inertia as Measured by POMS | Profile of Mood States (POMS) measures a variety of mood states including tension/anxiety, depression/dejection, anger/hostility, vigor/activity, fatigue/inertia and confusion/bewilderment. Each subscale consist of 5 items with a 5 points-scale (0=not at all, 1=a little, 2=moderately, 3=quite a bit and 4=extremely). The subscale scores were the sum of all five items. The scores were then transformed into a 100-point scale with higher numbers indicating less fatigue. Change from baseline to week 4 was calculated by subtracting the baseline scores from the scores at week 4. | Baseline and Week 4 | 
| Change From Baseline to Week 4 for the Impact on Stress as Measured by Perceived Stress Scale (PSS) | PSS consist of 14 items that assess the impact on stress in a 5-points scale (0=never, 1=almost never, 2=sometimes, 3=fairly often and 4=very often). The total scores were the sum of all 14 items. The scores were then transformed into a 100-point scale with higher numbers indication less stress. Change from baseline to week 4 was calculated by subtracting the baseline scores from the scores at week 4. | Baseline and Week 4 | 
| Change From Baseline to Week 8 in the Impact on General, Physical, Mental, and Emotional States and Vigor as Measured by Other Subscales of the MFSI-SF | Each MFSI-SF subscale consist of 6 items on a 5-point scale, ranging from 0 (not at all) to 4 (extremely). The subscale scores were the sum of all six items. The scores were then converted to a 100-point scale, with higher numbers indicating less fatigue. Change from baseline to week 8 was calculated by subtracting the baseline scores from the scores at week 8. | Baseline and week 8 | 
| Change From Baseline to Week 8 Fatigue as Measured by the BFI and Linear Analogue Scale of Fatigue | Brief Fatigue Inventory (BFI) consist of 3 items that assess the severity of fatigue and 6 items that assess the impact of fatigue on daily functioning in a 10-points scale with 0 as no fatigue or does not interfere with daily functioning and 10 as bad fatigue or completely interferes. The scores for the six items were summed up to form a total interference score. The linear analogue scale of fatigue was a 10-points scale with 0 as no fatigue and 10 as bad fatigue. All scores were then transformed into 0 to 100 scale, with 100 as less fatigue/less interference. Change from baseline to week 8 was calculated by subtracting the baseline scores from the scores at week 8. | Baseline and Week 8 | 
| Change From Baseline to Week 8 Vigor/Activity and Fatigue-inertia as Measured by POMS | Profile of Mood States (POMS) measures a variety of mood states including tension/anxiety, depression/dejection, anger/hostility, vigor/activity, fatigue/inertia and confusion/bewilderment. Each subscale consist of 5 items with a 5 points-scale (0=not at all, 1=a little, 2=moderately, 3=quite a bit and 4=extremely). The subscale scores were the sum of all five items. The scores were then transformed into a 100-point scale with higher numbers indicating less fatigue. Change from baseline to week 8 was calculated by subtracting the baseline scores from the scores at week 8. | Baseline and week 8 | 
| Change From Baseline to Week 8 for the Impact on Stress as Measured by Perceived Stress Scale (PSS) | PSS consist of 14 items that assess the impact on stress in a 5-points scale (0=never, 1=almost never, 2=sometimes, 3=fairly often and 4=very often). The total scores were the sum of all 14 items. The scores were then transformed into a 100-point scale with higher numbers indication less stress. Change from baseline to week 8 was calculated by subtracting the baseline scores from the scores at week 8. | Baseline and Week 8 | 
| Average Change From Baseline to Week 4 in Fatigue for Those Who Perceive a Change of +2 and +3 | Changes in fatigue as measured using subscales of MFSI-SF, the interference scale of the BFI and the linear analogue scale (LASA) fatigue question were compared between arms for those participants who express a perceived change in fatigue via the global impression score of a +2 (moderately better) and +3 (very much better). | Baseline and Week 4 | 
| Average Change From Baseline to Week 8 in Fatigue for Those Who Perceive a Change of +2 and +3 | Changes in fatigue as measured using subscales of MFSI-SF, the interference scale of the BFI and the linear analogue scale fatigue question were compared between arms for those participants who express a perceived change in fatigue via the global impression score of a +2 (moderately better) and +3 (very much better). | Baseline and Week 8 | 
| Change From Baseline to Week 4 in the General Subscale of the MFSI-SF for Minority Populations | Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) general subscale is a six-item subscale to measure the subjective experience of fatigue. The items include feeling pooped, worn out, fatigued, sluggish, run down and tired. Answers are on a 5-point scale, ranging from 0 (not at all) to 4 (extremely). The subscale scores were the sum of all six items. The scores were converted to a 100-point scale, with higher numbers indicating less fatigue. Change from baseline to week 4 was calculated by subtracting the baseline scores from the scores at week 4. | Baseline and Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV adult Hodgkin lymphoma, fatigue, unspecified adult solid tumor, protocol specific, accelerated phase chronic myelogenous leukemia, acute undifferentiated leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), atypical chronic myeloid leukemia, BCR-ABL1 negative, blastic phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, mast cell leukemia, progressive hairy cell leukemia, initial treatment, prolymphocytic leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult T-cell leukemia/lymphoma, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, stage 0 chronic lymphocytic leukemia, stage I adult T-cell leukemia/lymphoma, stage I chronic lymphocytic leukemia, stage II adult T-cell leukemia/lymphoma, stage II chronic lymphocytic leukemia, stage III adult T-cell leukemia/lymphoma, stage III chronic lymphocytic leukemia, stage IV adult T-cell leukemia/lymphoma, stage IV chronic lymphocytic leukemia, T-cell large granular lymphocyte leukemia, untreated adult acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous B-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, Waldenström macroglobulinemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, contiguous stage II adult lymphoblastic lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II grade 3 follicular lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II marginal zone lymphoma, contiguous stage II small lymphocytic lymphoma, stage I adult Burkitt lymphoma, stage I adult diffuse large cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage I mantle cell lymphoma, stage I marginal zone lymphoma, stage I small lymphocytic lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, intraocular lymphoma, post-transplant lymphoproliferative disorder, chronic eosinophilic leukemia, chronic neutrophilic leukemia, primary myelofibrosis, essential thrombocythemia, polycythemia vera, extramedullary plasmacytoma, isolated plasmacytoma of bone, monoclonal gammopathy of undetermined significance, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, primary systemic amyloidosis, refractory multiple myeloma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable