Quality of Life
Conditions
Brief summary
This study is examine the effect of the addition of naturopathic on immunologic and/or inflammatory parameters and/or quality of life in women receiving neoadjuvant chemotherapy for breast cancer.
Interventions
BIOLOGICALReishi mushroom extract
Reishi mushroom preparation produced water-ethanol extraction.
DRUGCoenzyme Q10
Preparation of coenzyme Q10
DRUGMelatonin
Preparation of melatonin
Sponsors
Midwestern Regional Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female * 18 years or older * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 * Biopsy proven diagnosis of invasive adenocarcinoma of the breast * Recommendation for neoadjuvant chemotherapy. * Left Ventricular Ejection Fraction (LVEF) assessment by multigated acquisition scan or echocardiogram within 3 months of entering study * Blood counts: * Absolute Neutrophil Count ≥1200 cells/mm\^3 * Platelet count ≥100,000/mm\^3 * Hemoglobin ≥10g/dL * Serum creatinine ≤ Upper Limit of Normal (ULN) for the laboratory range * Total bilirubin ≤ ULN for the laboratory range, unless the patient has an elevation \>ULN to 1.5 times the ULN resulting from Gilbert's disease or similar syndrome * Alkaline phosphatase less than or equal to 2.5 x ULN; and * Aspartate aminotransferase (AST) less than or equal to 1.5 x ULN for the laboratory range * If skeletal pain present or alkaline phosphatase \>ULN (but less than or equal to 2.5x ULN), bone scan or Positron Emission Tomography (PET) scan must not demonstrate metastatic disease * AST or alkaline phosphatase greater than ULN, no metastatic disease liver identified by CT, MRI or PET scan * Able to swallow oral medication * Willing to forego naturopathic treatment for the first 2 treatment cycles * Willing to start and continue naturopathic interventions as prescribed * Willing to forego the use of nutritional or botanical supplements during the study
Exclusion criteria
* Stage 4 disease * Present treatment with Warfarin. * Synchronous bilateral invasive breast cancer * Treatment including radiation, chemotherapy, and/or targeted therapy for the currently diagnosed breast cancer prior to entering study * Any sex hormonal therapy e.g. birth control, ovarian hormone replacement therapy, etc. during participation in the study) * Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators * Prior history of breast cancer, including Ductal Carcinoma In Situ (subjects with a history of Lobular Carcinoma In Situ are eligible) * Prior therapy with chemotherapy or targeted therapy agents for any malignancy * Cardiac disease that would preclude the use of the certain drugs. This includes but is not confined to: * Active cardiac disease * Angina pectoris requiring treatment * Ventricular arrhythmias except controlled benign premature ventricular contractions * Conduction abnormality requiring a pacemaker * Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled by medication * Clinical significant valvular disease * History of cardiac disease * Myocardial infarction * Congestive heart failure * Cardiomyopathy * Uncontrolled hypertension, (blood pressure above 150/90 mm/Hg on antihypertensive treatment) * History or current symptomatic interstitial pneumonitis or pulmonary fibrosis * Sensory/motor neuropathy ≥ grade 2 * Malabsorption syndrome, ulcerative colitis, resection the stomach or small bowel, or other disease significantly affecting gastrointestinal function * Other non-malignant systemic disease precluding treatment with study regimens or required follow up * Contraindication of corticosteroids * Administration of an investigational agent within 30 days prior to entering study. * Administration of therapeutic doses of the supplements being studied including maitake, melatonin and Coenzyme Q10 in the previous 30 days. * Administration of therapeutic doses of immune modulating botanicals in the previous 30 days. * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject Reported Quality of Life Score | Initial visit and study visits at 3-week intervals up to 4 months | Subject quality of life as measured by a self-administered questionnaire (0 to 10 Likert scale with 0=No Effect to 10=Worst Effect) at each study visit. The symptoms or impact on activities scored included: Pain, Fatigue, Nausea, Sleep Disturbance, Distress, Shortness of Breath, Memory/Recall Problems, Appetite, Drowsiness, Dry Mouth, Sadness, Vomiting, Numbness, General Activities, Mood, Work, Relationships, Walking or Enjoyment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of C-reactive Protein in Serum (mg/L) | Initial visit and study visits at 3-week intervals up to 4 months | The serum concentration of C-reactive protein will be measured by approved methods. |
| Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Initial visit and study visits at 3-week intervals up to 4 months | The serum concentration of circulating tumor cells will be measured by approved methods. |
| Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Initial visit and study visits at 3-week intervals up to 4 months | The erythrocyte sedimentation rate will be measured by approved methods. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Immediate and Continuous Dosing Subjects will be dosed with Reishi mushroom extract, Coenzyme Q10 and Melatonin beginning with Cycle 1 Day 1 of their prescribed neoadjuvant chemotherapy.
Reishi mushroom extract: Reishi mushroom preparation produced water-ethanol extraction.
Coenzyme Q10: Preparation of coenzyme Q10
Melatonin: Preparation of melatonin | 3 |
| Delayed Dosing Subjects will be dosed with Reishi mushroom extract, Coenzyme Q10 and Melatonin beginning with Cycle 3 Day 1 of their prescribed neoadjuvant chemotherapy.
Reishi mushroom extract: Reishi mushroom preparation produced water-ethanol extraction.
Coenzyme Q10: Preparation of coenzyme Q10
Melatonin: Preparation of melatonin | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Immediate and Continuous Dosing | Delayed Dosing | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
Subject Reported Quality of Life Score
Subject quality of life as measured by a self-administered questionnaire (0 to 10 Likert scale with 0=No Effect to 10=Worst Effect) at each study visit. The symptoms or impact on activities scored included: Pain, Fatigue, Nausea, Sleep Disturbance, Distress, Shortness of Breath, Memory/Recall Problems, Appetite, Drowsiness, Dry Mouth, Sadness, Vomiting, Numbness, General Activities, Mood, Work, Relationships, Walking or Enjoyment.
Time frame: Initial visit and study visits at 3-week intervals up to 4 months
Population: One subject in the 'Delayed' arm withdrew consent following Study Visit 2. One subject in the 'Immediate' arm did not complete the Quality of Life Questionnaire at Visit 2. One subject in the 'Delayed' arm did not complete the Quality of Life Questionnaire at Visit 5. One subject in the 'Immediate' Arm withdrew consent prior to completing Visit 5.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 1) | 1.7 units on a scale | Standard Deviation 1.7 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 5) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 3) | 1.7 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 5) | 3.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 1) | 2.3 units on a scale | Standard Deviation 1.2 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 3) | 1.0 units on a scale | Standard Deviation 0.8 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 5) | 3.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 5) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 1) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 3) | 1.0 units on a scale | Standard Deviation 0.8 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 5) | 2.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 1) | 0.7 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 3) | 2.0 units on a scale | Standard Deviation 2.8 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 4) | .05 units on a scale | Standard Deviation 0.05 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 5) | 2.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 1) | 1.0 units on a scale | Standard Deviation 0.8 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 3) | 1.0 units on a scale | Standard Deviation 0.8 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 5) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 3) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 15 | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 1) | 1.3 units on a scale | Standard Deviation 1.2 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 3) | 0.3 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 5) | 2.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 3) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 5) | 2.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 2) | 1.5 units on a scale | Standard Deviation 1.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 3) | 1.0 units on a scale | Standard Deviation 1.4 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 5) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 3) | 0.7 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 5) | 2.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 1) | 1.7 units on a scale | Standard Deviation 1.2 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 3) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 5) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 1) | 1.0 units on a scale | Standard Deviation 1.4 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 3) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 5) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 1) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 3) | 0.7 units on a scale | Standard Deviation 0.7 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Enjoyment (Visit 1) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Enjoyment (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | 1Worst Effect on Enjoyment (Visit 3) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Enjoyment (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Effect on Enjoyment (Visit 5) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 5) | 2.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Pain (Visit 1) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst pain (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Pain (Visit 3) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Pain (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Pain (Visit 5) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 1) | 1.0 units on a scale | Standard Deviation 0.8 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 3) | 1.3 units on a scale | Standard Deviation 1.2 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 4) | 1.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 5) | 1.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 1) | 0.7 units on a scale | Standard Deviation 0.9 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 3) | 0.3 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 4) | 0.5 units on a scale | Standard Deviation 0.5 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 5) | 3.0 units on a scale | Standard Deviation 0 |
| Immediate and Continuous Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 1) | 3.3 units on a scale | Standard Deviation 0.9 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 2) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 1) | 1.5 units on a scale | Standard Deviation 0.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Enjoyment (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Pain (Visit 1) | 2.0 units on a scale | Standard Deviation 1 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 2) | 2.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst pain (Visit 2) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 1) | 2.0 units on a scale | Standard Deviation 1 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Pain (Visit 3) | 2.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 3) | 3.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Pain (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Drowsiness (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 1) | 1.5 units on a scale | Standard Deviation 0.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 1) | 2.0 units on a scale | Standard Deviation 2 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 2) | 3.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 3) | 2.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 3) | 3.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 1) | 0.5 units on a scale | Standard Deviation 0.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Fatigue (Visit 4) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Enjoyment (Visit 1) | 1.5 units on a scale | Standard Deviation 0.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 2) | 1.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on General Activities (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 2) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 3) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Nausea (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Dry Mouth (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 1) | 3.0 units on a scale | Standard Deviation 1 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 1) | 2.0 units on a scale | Standard Deviation 2 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 1) | 1.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 3) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Disturbance (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 2) | 1.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 2) | 2.0 units on a scale | Standard Deviation 1 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 1) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 2) | 1.0 units on a scale | Standard Deviation 1 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sadness (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Sleep Distress (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | 1Worst Effect on Enjoyment (Visit 3) | 2.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Mood (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 3) | 2.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Shortness of Breath (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Vomiting (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 1) | 2.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Walking (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 2) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 3) | 2.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 1) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Memory/Recall (Visit 4) | 3.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Relationships (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 2) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 1) | 1.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 2) | 0.5 units on a scale | Standard Deviation 0.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 2) | 1.5 units on a scale | Standard Deviation 1.5 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 3) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Enjoyment (Visit 2) | 1.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Appetite (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Numbness (Visit 4) | 0.0 units on a scale | Standard Deviation 0 |
| Delayed Dosing | Subject Reported Quality of Life Score | Worst Effect on Work (Visit 3) | 2.0 units on a scale | Standard Deviation 0 |
Secondary
Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter)
The serum concentration of circulating tumor cells will be measured by approved methods.
Time frame: Initial visit and study visits at 3-week intervals up to 4 months
Population: Circulating tumor cells were not determined for one subject in the 'Immediate' Arm at Visit 1, one subject in the 'Delayed' Arm at Visit 2 and one subject in the 'Immediate' Arm at Visit 3 due to blood sample not collected. One subject in each arm withdrew consent after visits 2 and 4, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate and Continuous Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 2 | 0.0 cells/ml | Standard Deviation 0 |
| Immediate and Continuous Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 4 | 0.0 cells/ml | Standard Deviation 0 |
| Immediate and Continuous Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 3 | 0.0 cells/ml | Standard Deviation 0 |
| Immediate and Continuous Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 5 | 0.0 cells/ml | Standard Deviation 0 |
| Immediate and Continuous Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 1 | 0.0 cells/ml | Standard Deviation 0 |
| Delayed Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 5 | 0.0 cells/ml | Standard Deviation 0 |
| Delayed Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 1 | 0.0 cells/ml | Standard Deviation 0 |
| Delayed Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 2 | 0.0 cells/ml | Standard Deviation 0 |
| Delayed Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 3 | 0.0 cells/ml | Standard Deviation 0 |
| Delayed Dosing | Concentration of Circulating Tumor Cells in Blood (Cells Per Milliliter) | Visit 4 | 0.0 cells/ml | Standard Deviation 0 |
Secondary
Concentration of C-reactive Protein in Serum (mg/L)
The serum concentration of C-reactive protein will be measured by approved methods.
Time frame: Initial visit and study visits at 3-week intervals up to 4 months
Population: C-reactive protein was not determined for one subject in the 'Immediate' Arm at Visit 1, one subject in the 'Delayed' Arm at Visit 2 and one subject in the 'Immediate' Arm at Visit 3 due to blood sample not collected. One subject in each arm withdrew consent after visits 2 and 4, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate and Continuous Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 2 | 0.50 mg/dl | Standard Deviation 0.12 |
| Immediate and Continuous Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 4 | 0.40 mg/dl | Standard Deviation 0.1 |
| Immediate and Continuous Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 3 | 0.30 mg/dl | Standard Deviation 0.1 |
| Immediate and Continuous Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 5 | 0.30 mg/dl | Standard Deviation 0 |
| Immediate and Continuous Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 1 | 0.20 mg/dl | Standard Deviation 0 |
| Delayed Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 5 | 0.10 mg/dl | Standard Deviation 0 |
| Delayed Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 1 | 0.15 mg/dl | Standard Deviation 0.05 |
| Delayed Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 2 | 0.03 mg/dl | Standard Deviation 0 |
| Delayed Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 3 | 0.03 mg/dl | Standard Deviation 0 |
| Delayed Dosing | Concentration of C-reactive Protein in Serum (mg/L) | Visit 4 | 0.03 mg/dl | Standard Deviation 0 |
Secondary
Sedimentation Rate of Erythrocytes in Blood (mm/hr)
The erythrocyte sedimentation rate will be measured by approved methods.
Time frame: Initial visit and study visits at 3-week intervals up to 4 months
Population: Sedimentation rate was not determined for one subject in the 'Immediate' Arm at Visit 1, one subject in the 'Delayed' Arm at Visit 2 and one subject in the 'Immediate' Arm at Visit 3 due to blood sample not collected. One subject in each arm withdrew consent after visits 2 and 4, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate and Continuous Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 2 | 17.3 mm/hr | Standard Deviation 8.3 |
| Immediate and Continuous Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 4 | 14.0 mm/hr | Standard Deviation 0 |
| Immediate and Continuous Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 3 | 20.5 mm/hr | Standard Deviation 9.5 |
| Immediate and Continuous Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 5 | 13.0 mm/hr | Standard Deviation 0 |
| Immediate and Continuous Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 1 | 13.5 mm/hr | Standard Deviation 9.5 |
| Delayed Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 5 | 18.0 mm/hr | Standard Deviation 0 |
| Delayed Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 1 | 17.0 mm/hr | Standard Deviation 7 |
| Delayed Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 2 | 11.0 mm/hr | Standard Deviation 0 |
| Delayed Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 3 | 13.0 mm/hr | Standard Deviation 0 |
| Delayed Dosing | Sedimentation Rate of Erythrocytes in Blood (mm/hr) | Visit 4 | 16.0 mm/hr | Standard Deviation 0 |