Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Unresectable Malignant Neoplasm
Conditions
Brief summary
This phase I trial studies the side effects and the best dose of muscadine grape skin extract (MGE) in treating patients with malignancy (tumor or cancer) that has spread to other parts of the body or cannot be removed by surgery. MGE is a nutritional supplement containing an extract of the skin of muscadine grape that has shown anti-cancer activity in laboratory studies and may be able to fight or kill malignant cells.
Detailed description
PRIMARY OBJECTIVES: I. To determine the safety and maximum tolerated dose (MTD) of MGE (muscadine grape skin extract) after 4 weeks of administration for patients with metastatic cancer. Secondary Objectives: I. To monitor adverse events/toxicity every 4 weeks while on treatment. II. To evaluate change in phenolic levels (total and component, blood and urine) from baseline to 4 and 8 weeks. III. To evaluate change in serum cytokines and growth factors from baseline to 4 and 8 weeks on MGE. IV. To observe the response rate of MGE in patients with metastatic cancer. V. To assess overall and progression-free survival in patients with metastatic cancer receiving MGE. VI. To assess global quality of life (Functional Assessment of Cancer Therapy-General \[FACT-G\] and fatigue (Patient Reported Outcomes Measurement Information System \[PROMIS\]-fatigue Short Form \[SF\]) in cancer patients taking MGE. VII. To assess adherence to MGE treatment. OUTLINE: This is a dose-escalation study. Patients receive muscadine grape skin extract orally (PO) twice daily (BID). Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 6 weeks.
Interventions
DIAGNOSTIC_TESTLaboratory Biomarker Analysis
Correlative studies
DRUGMuscadine Grape Skin Extract
Given PO
PROCEDUREQuality-of-Life Assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed malignancy that is metastatic or unresectable and have failed standard therapies * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Absolute neutrophil count \>= 1000/mcL * Platelets \>= 50,000/mcL * Total bilirubin within normal institutional limits * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit or normal * Creatinine clearance \>= 40 mL/min * Stable supplement usage for \> 2 weeks prior to starting and agrees not to change while on this study * Life expectancy \> 3 months
Exclusion criteria
* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier * Patients may not be receiving any other investigational cancer-directed agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to MGE * Patients unable to take oral medications or those with history of malabsorption due to bowel resection * Patients with uncontrolled diarrhea or persistent nausea/vomiting requiring daily antiemetic therapy for symptom management * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study; breastfeeding should be discontinued * Patients with primary brain tumors are excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicity | 29 days | Maximum tolerable dose of muscadine grape extract is defined as the dose level immediately below the dose level that induced a dose-limiting toxicity (DLT) in \>= 2 patients, as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0DLT will be assessed by severity of adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Response | At the end of treatment, up to 1 year | Best response will be characterized using a frequency table. Evaluation of new or enlarging effusions to differentiate between Progressive Disease and Response/Stable Disease. Measurements will be obtained from usual care imaging and assessed by the principal investigators in confirmation with the physician of record. Clinical lesions will only be considered measurable when they are superficial and ≥10 mm in diameter as assessed using calipers. For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended. |
| Change in Total Phenolic Levels in Blood | Baseline to up to 8 weeks | A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8. |
| Change in Total Phenolic Levels in Urine | Baseline to up to 8 weeks | A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8. |
| Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Baseline to up to 1 year | A mixed model ANOVA model will be fit with phenolic level as the outcome and time (baseline, every 4 weeks) as a fixed effect and subject as a random effect. Contrasts will be use to estimate changes from baseline to each follow-up time period. Score scales from 0 (not at all) to 4 (very much). Sum of scores range 0-28 for social, functional and physical well being and 0-24 for emotional well being and multiplied by 6. All four scores are totaled with a score range of 0-108. A mean of the combined group scores will be used. A higher score indicates a higher worse outcome of the illness on the participant. |
| Change in Systemic Cytokine Levels | Baseline to up to 8 weeks | A mixed model ANOVA model will fit with the outcome of interest (cytokine or growth factor) as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8. |
| Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0 | Up to 1 year | AEs/toxicity will be assessed at weeks 4, 8 and every 4 weeks thereafter if patients remain on treatment. Any expected toxicities, any laboratory based toxicities, and any grade 3 or higher gastrointestinal toxicities, and any grade 4 or higher toxicities will be summarized using frequency tables overall and by week. |
| Overall Response Rate of MGE (Complete Response, Partial Response, and Stable Disease) | At 8 weeks | Response will be characterized using a frequency table. |
| Adherence to MGE Treatment, as Measured by Percent of Pills Taken at the End of Every 4 Week Period | Up to 1 year | Pill count will be calculated from counting the number of pills returned as well as by summarizing the patient's pill diary. The percent of pills taken will be summarized by dose level using the median and 95% confidence interval. Investigators will summarize the percent of pills taken at the end of every 4 week period i using the formula: Percent of pills taken)i = (Dose Level ×7 ×4)i minus Pill Count divided by Dose Level ×7 ×4)i |
| Progression-free Survival (PFS) | Up to 4 years | PFS will summarized using the Kaplan-Meier method. |
| Change in Component Phenolic Levels in Urine | Baseline to up to 8 weeks | A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8. |
| Change in Component Phenolic Levels in Blood | Baseline to up to 8 weeks | A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8. |
| Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by PROMIS-Fatigue SF | Baseline to up to 1 year | A mixed model ANOVA model will be fit with phenolic level as the outcome and time (baseline, every 4 weeks) as a fixed effect and subject as a random effect. Contrasts will be use to estimate changes from baseline to each follow-up time period. A 6-item questionnaire with T-score responses ranging from a minimum of 33.4 to a maximum of 76.8. Higher scores equals more of the concept being measured. |
| Change in Systemic Cytokine Levels (Log IL-8) | Baseline to up to 8 weeks | A mixed model ANOVA model will fit with the outcome of interest (cytokine or growth factor) as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8. |
| Change in Systemic Cytokine Levels (Log VEGF) | Baseline to up to 8 weeks | A mixed model ANOVA model will fit with the outcome of interest (cytokine or growth factor) as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8. |
| Overall Survival (OS) | Up to 4 years | OS will summarized using the Kaplan-Meier method. Median survival rates and associated 95% confidence intervals will be calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill Times a Day Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Muscadine Grape Skin Extract: Given PO
Quality-of-Life Assessment: Ancillary studies | 3 |
| Arm 2 (Muscadine Grape Skin Extract) 2 Pills Times a Day Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Muscadine Grape Skin Extract: Given PO
Quality-of-Life Assessment: Ancillary studies | 7 |
| Arm 3 (Muscadine Grape Skin Extract) 3 Pills Times a Day Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Muscadine Grape Skin Extract: Given PO
Quality-of-Life Assessment: Ancillary studies | 3 |
| Arm 4 (Muscadine Grape Skin Extract) 4 Pills Times a Day Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Muscadine Grape Skin Extract: Given PO
Quality-of-Life Assessment: Ancillary studies | 5 |
| Arm 5 (Muscadine Grape Skin Extract) 5 Pills Times a Day Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Muscadine Grape Skin Extract: Given PO
Quality-of-Life Assessment: Ancillary studies | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Patient hospitalized prior to start | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1 (Muscadine Grape Skin Extract) 1 Pill Times a Day | Total | Arm 5 (Muscadine Grape Skin Extract) 5 Pills Times a Day | Arm 4 (Muscadine Grape Skin Extract) 4 Pills Times a Day | Arm 3 (Muscadine Grape Skin Extract) 3 Pills Times a Day | Arm 2 (Muscadine Grape Skin Extract) 2 Pills Times a Day |
|---|---|---|---|---|---|---|
| Age, Continuous | 81.3 years STANDARD_DEVIATION 3.29 | 69.8 years STANDARD_DEVIATION 12.2 | 70 years STANDARD_DEVIATION 11.8 | 64 years STANDARD_DEVIATION 7.13 | 62.6 years STANDARD_DEVIATION 6.24 | 73.4 years STANDARD_DEVIATION 13.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 24 Participants | 6 Participants | 5 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 23 Participants | 6 Participants | 5 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United States | 3 participants | 24 participants | 6 participants | 5 participants | 3 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 10 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 14 Participants | 4 Participants | 2 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 6 | 0 / 3 | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 1 / 6 | 0 / 3 | 0 / 3 | 1 / 6 |
Outcome results
Primary
Number of Participants With Dose-Limiting Toxicity
Maximum tolerable dose of muscadine grape extract is defined as the dose level immediately below the dose level that induced a dose-limiting toxicity (DLT) in \>= 2 patients, as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0DLT will be assessed by severity of adverse events.
Time frame: 29 days
Population: As pre-specified in the protocol, data collection and analysis for all arms will be combined. MTD was not determined, as there was not a dose level with ≥2 dose limiting toxicities (DLT). One DLT at dose level 2 and therefore 3 additional participants were enrolled. No subsequent DLTs and the study was stopped at dose level 5, per protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Number of Participants With Dose-Limiting Toxicity | 0 Participants |
| Arm 2 (Muscadine Grape Skin Extract) 2 Pills 2 Times a Day | Number of Participants With Dose-Limiting Toxicity | 1 Participants |
| Arm 3 (Muscadine Grape Skin Extract) 3 Pills 2 Times a Day | Number of Participants With Dose-Limiting Toxicity | 0 Participants |
| Arm 4 (Muscadline Grape Skin Extract) 4 Pills 2 Times a Day | Number of Participants With Dose-Limiting Toxicity | 0 Participants |
| Arm 5 (Muscadine Grape Skin Extract) 5 Pills 2 Times a Day | Number of Participants With Dose-Limiting Toxicity | 0 Participants |
Secondary
Adherence to MGE Treatment, as Measured by Percent of Pills Taken at the End of Every 4 Week Period
Pill count will be calculated from counting the number of pills returned as well as by summarizing the patient's pill diary. The percent of pills taken will be summarized by dose level using the median and 95% confidence interval. Investigators will summarize the percent of pills taken at the end of every 4 week period i using the formula: Percent of pills taken)i = (Dose Level ×7 ×4)i minus Pill Count divided by Dose Level ×7 ×4)i
Time frame: Up to 1 year
Population: As pre-specified in the protocol, this study is not intended to be analyzed by arm for most analyses and data collection. Analysis for all arms will be combined for Adherence to EMG treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Adherence to MGE Treatment, as Measured by Percent of Pills Taken at the End of Every 4 Week Period | 97.8 percentage of pills |
Secondary
Best Response
Best response will be characterized using a frequency table. Evaluation of new or enlarging effusions to differentiate between Progressive Disease and Response/Stable Disease. Measurements will be obtained from usual care imaging and assessed by the principal investigators in confirmation with the physician of record. Clinical lesions will only be considered measurable when they are superficial and ≥10 mm in diameter as assessed using calipers. For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended.
Time frame: At the end of treatment, up to 1 year
Population: As pre-specified in the protocol, this study is not intended to be analyzed by arm for most analyses and data collection. Analysis for all arms will be combined for Best Response
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Best Response | Stable Disease | 8 Participants |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Best Response | Progressive Disease | 8 Participants |
Secondary
Change in Component Phenolic Levels in Blood
A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.
Time frame: Baseline to up to 8 weeks
Population: Outcome measure was not measured
Secondary
Change in Component Phenolic Levels in Urine
A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.
Time frame: Baseline to up to 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Component Phenolic Levels in Urine | Baseline | 0.4 ug/ml | Standard Error 7.9 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Component Phenolic Levels in Urine | Week 4 | 19.7 ug/ml | Standard Error 8.2 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Component Phenolic Levels in Urine | Week 8 | 16.6 ug/ml | Standard Error 8.6 |
Secondary
Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G
A mixed model ANOVA model will be fit with phenolic level as the outcome and time (baseline, every 4 weeks) as a fixed effect and subject as a random effect. Contrasts will be use to estimate changes from baseline to each follow-up time period. Score scales from 0 (not at all) to 4 (very much). Sum of scores range 0-28 for social, functional and physical well being and 0-24 for emotional well being and multiplied by 6. All four scores are totaled with a score range of 0-108. A mean of the combined group scores will be used. A higher score indicates a higher worse outcome of the illness on the participant.
Time frame: Baseline to up to 1 year
Population: As pre-specified in the protocol, this study is not intended to be analyzed by arm for most analyses and data collection. Analysis for all arms will be combined for change in quality of life. All participants did not complete intervention for outcome measures are various time points (i.e., week 4 and week 8)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | FACT-G Overall Score - at Baseline | 80.6 score on a scale | Standard Error 3.9 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Fact G - Overall Score - at Week 4 | 79.4 score on a scale | Standard Error 3.9 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Fact G - Overall Score - at Week 8 | 81.1 score on a scale | Standard Error 4 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Functional well being - at Baseline | 17.7 score on a scale | Standard Error 1.6 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Functional well being - at Week 4 | 17.7 score on a scale | Standard Error 1.6 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Functional well being - at Week 8 | 16.5 score on a scale | Standard Error 1.7 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Emotional Well being - at Baseline | 17.8 score on a scale | Standard Error 0.9 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Emotional well being - at Week 4 | 17.8 score on a scale | Standard Error 0.9 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Emotional well being - at Week 8 | 18.8 score on a scale | Standard Error 1 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Physical well being - at Baseline | 20.6 score on a scale | Standard Error 1.5 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Physical well being - at Week 4 | 19.3 score on a scale | Standard Error 1.5 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Physical well being - at Week 8 | 20.4 score on a scale | Standard Error 1.6 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Social well being - at Baseline | 24.5 score on a scale | Standard Error 0.7 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Social well being - at Week 4 | 24.9 score on a scale | Standard Error 0.7 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G | Social well being - at Week 8 | 25.4 score on a scale | Standard Error 0.8 |
Comparison: Overall FACT G score p value baseline to week 8p-value: 0.76ANOVA
Comparison: Fact G functional well being p value baseline to week 8p-value: 0.25ANOVA
Comparison: FACT G emotional well being p value baseline to week 8p-value: 0.18ANOVA
Comparison: Fact G physical well being p value baseline to week 8p-value: 0.87ANOVA
Comparison: Fact G social well being p value baseline to week 8p-value: 0.22ANOVA
Secondary
Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by PROMIS-Fatigue SF
A mixed model ANOVA model will be fit with phenolic level as the outcome and time (baseline, every 4 weeks) as a fixed effect and subject as a random effect. Contrasts will be use to estimate changes from baseline to each follow-up time period. A 6-item questionnaire with T-score responses ranging from a minimum of 33.4 to a maximum of 76.8. Higher scores equals more of the concept being measured.
Time frame: Baseline to up to 1 year
Population: As pre-specified in the protocol, this study is not intended to be analyzed by arm for most analyses and data collection. Analysis for all arms will be combined for change in quality of life. Not all participants completed intervention at the week 4 and week 8 time frames to be analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by PROMIS-Fatigue SF | Baseline | 56.2 T-score | Standard Error 2.5 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by PROMIS-Fatigue SF | Week 4 | 57.3 T-score | Standard Error 2.6 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by PROMIS-Fatigue SF | Week 8 | 55.3 T-score | Standard Error 2.7 |
p-value: 0.67ANOVA
Secondary
Change in Systemic Cytokine Levels
A mixed model ANOVA model will fit with the outcome of interest (cytokine or growth factor) as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.
Time frame: Baseline to up to 8 weeks
Population: Arms were combined for cytokine and phenolic analyses as pre-specified per protocol
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Baseline to Week 8 IL-1 alpha | NA pg/mL | — |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Baseline to 8 weeks IL-1 beta | NA pg/mL | — |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Baseline to 8 weeks IL-6 | NA pg/mL | — |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Baseline TNF alpha | 4.74 pg/mL | Standard Error 0.39 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Week 4 TNF alpha | 4.95 pg/mL | Standard Error 0.39 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Week 8 TNF alpha | 4.97 pg/mL | Standard Error 0.41 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Baseline IL-6R | 10905.9 pg/mL | Standard Error 1013.7 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Week 4 IL-6R | 11111.7 pg/mL | Standard Error 993.7 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels | Week 8 IL-6R | 12402.9 pg/mL | Standard Error 1077.9 |
Secondary
Change in Systemic Cytokine Levels (Log IL-8)
A mixed model ANOVA model will fit with the outcome of interest (cytokine or growth factor) as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.
Time frame: Baseline to up to 8 weeks
Population: Arms were combined for cytokine and phenolic analyses as pre-specified per protocol
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels (Log IL-8) | Baseline Log IL-8 | 1.49 log pg/mL | Standard Error 0.16 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels (Log IL-8) | Week 4 Log IL-8 | 1.32 log pg/mL | Standard Error 0.17 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels (Log IL-8) | Week 8 Log IL-8 | 1.40 log pg/mL | Standard Error 0.17 |
Comparison: Baseline v. 4 weeks log IL-8p-value: 0.119ANOVA
Comparison: Baseline v. 8 weeks log IL-8p-value: 0.414ANOVA
Secondary
Change in Systemic Cytokine Levels (Log VEGF)
A mixed model ANOVA model will fit with the outcome of interest (cytokine or growth factor) as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.
Time frame: Baseline to up to 8 weeks
Population: Arms were combined for cytokine and phenolic analyses as pre-specified per protocol
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels (Log VEGF) | Baseline Log VEGF | 2.78 log pg/mL | Standard Error 0.23 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels (Log VEGF) | Week 4 Log VEGF | 2.81 log pg/mL | Standard Error 0.23 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Systemic Cytokine Levels (Log VEGF) | Week 8 Log VEGF | 2.84 log pg/mL | Standard Error 0.23 |
Comparison: Baseline v. 4 weeks p value log VEGFp-value: 0.851ANOVA
Comparison: Baseline vs. 8 weeks p value log VEGFp-value: 0.688ANOVA
Secondary
Change in Total Phenolic Levels in Blood
A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.
Time frame: Baseline to up to 8 weeks
Population: As pre-specified in the protocol, this study is not intended to be analyzed by arm for most analyses and data collection. Analysis for all arms will be combined for change in total phenolic levels in blood.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Total Phenolic Levels in Blood | Baseline | 2123.8 ug/ml | Standard Error 69.1 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Total Phenolic Levels in Blood | Week 4 | 2049.3 ug/ml | Standard Error 69.1 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Total Phenolic Levels in Blood | Week 8 | 2308.1 ug/ml | Standard Error 71.7 |
Secondary
Change in Total Phenolic Levels in Urine
A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.
Time frame: Baseline to up to 8 weeks
Population: Arms were combined for cytokine and phenolic analyses as pre-specified per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Total Phenolic Levels in Urine | Baseline | 1107.2 ug/ml | Standard Error 142.4 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Total Phenolic Levels in Urine | Week 4 | 1024.5 ug/ml | Standard Error 142.3 |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Change in Total Phenolic Levels in Urine | Week 8 | 1274.6 ug/ml | Standard Error 150.7 |
Secondary
Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0
AEs/toxicity will be assessed at weeks 4, 8 and every 4 weeks thereafter if patients remain on treatment. Any expected toxicities, any laboratory based toxicities, and any grade 3 or higher gastrointestinal toxicities, and any grade 4 or higher toxicities will be summarized using frequency tables overall and by week.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0 | 3 Participants |
| Arm 2 (Muscadine Grape Skin Extract) 2 Pills 2 Times a Day | Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0 | 3 Participants |
| Arm 3 (Muscadine Grape Skin Extract) 3 Pills 2 Times a Day | Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0 | 2 Participants |
| Arm 4 (Muscadline Grape Skin Extract) 4 Pills 2 Times a Day | Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0 | 2 Participants |
| Arm 5 (Muscadine Grape Skin Extract) 5 Pills 2 Times a Day | Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0 | 5 Participants |
Secondary
Overall Response Rate of MGE (Complete Response, Partial Response, and Stable Disease)
Response will be characterized using a frequency table.
Time frame: At 8 weeks
Population: As pre-specified in the protocol, data will be collected and analyzed for all arms combined. At 8 weeks, only 16 patients were evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Overall Response Rate of MGE (Complete Response, Partial Response, and Stable Disease) | Stable Disease | 8 Participants |
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Overall Response Rate of MGE (Complete Response, Partial Response, and Stable Disease) | Progressive Disease | 8 Participants |
Secondary
Overall Survival (OS)
OS will summarized using the Kaplan-Meier method. Median survival rates and associated 95% confidence intervals will be calculated.
Time frame: Up to 4 years
Population: As pre-specified in the protocol, this study is not intended to be analyzed by arm for most analyses and data collection. Analysis for all arms will be combined for overall survival.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Overall Survival (OS) | 7.2 months |
Secondary
Progression-free Survival (PFS)
PFS will summarized using the Kaplan-Meier method.
Time frame: Up to 4 years
Population: As pre-specified in the protocol, this study is not intended to be analyzed by arm for most analyses and data collection. Analysis for all arms will be combined for progression free survival.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day | Progression-free Survival (PFS) | 3.0 months |