Clinical trial NCT02583269: Muscadine Grape Skin Extract in Treating Patients With Malignancy That Is Metastatic or Cannot Be Removed by Surgery
Official title: Phase I Study of Muscadine Grape Extract (MGE) in Advanced Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Malignant Neoplasm
Metastatic Malignant Neoplasm
Unresectable Malignant Neoplasm
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-10-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicity
timeFrame: 29 days
Secondary outcomes:
measure: Adherence to MGE Treatment, as Measured by Percent of Pills Taken at the End of Every 4 Week Period
timeFrame: Up to 1 year
measure: Best Response
timeFrame: At the end of treatment, up to 1 year
measure: Change in Total Phenolic Levels in Blood
timeFrame: Baseline to up to 8 weeks
measure: Change in Total Phenolic Levels in Urine
timeFrame: Baseline to up to 8 weeks
measure: Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G
timeFrame: Baseline to up to 1 year
measure: Change in Systemic Cytokine Levels
timeFrame: Baseline to up to 8 weeks
measure: Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0
timeFrame: Up to 1 year
measure: Overall Response Rate of MGE (Complete Response, Partial Response, and Stable Disease)
timeFrame: At 8 weeks
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 4 years
measure: Change in Component Phenolic Levels in Urine
timeFrame: Baseline to up to 8 weeks
measure: Change in Component Phenolic Levels in Blood
timeFrame: Baseline to up to 8 weeks
measure: Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by PROMIS-Fatigue SF
timeFrame: Baseline to up to 1 year
measure: Change in Systemic Cytokine Levels (Log IL-8)
timeFrame: Baseline to up to 8 weeks
measure: Change in Systemic Cytokine Levels (Log VEGF)
timeFrame: Baseline to up to 8 weeks
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Heidi Klepin
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bitting RL, Tooze JA, Isom S, Petty WJ, Grant SC, Desnoyers RJ, Thomas A, Thomas CY, Alistar AT, Golden SL, Pleasant K, Chappell MC, Tallant EA, Gallagher PE, Klepin HD. Phase I Study of Muscadine Grape Extract for Patients With Advanced Cancer. Am J Clin Oncol. 2021 Jun 1;44(6):239-246. doi: 10.1097/COC.0000000000000814.