Clinical trial NCT06044025: A Feasibility Study Evaluating a Role for Maintenance Therapy in Patients With Biochemically Progressive Castration Sensitive Prostate Cancer on Intermittent Androgen Deprivation Therapy
Official title: A Feasibility Study Evaluating a Role for Maintenance Therapy in Patients With Biochemically Progressive Castration Sensitive Prostate Cancer on Intermittent Androgen Deprivation Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Castration Sensitive Prostate Cancer
Lead sponsor: University of Arkansas
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal of this clinical trial is to assess the feasibility of adding a combination of metformin and turmeric as part of a nutritional intervention regimen to the current standard of care, namely, intermittent Androgen Deprivation Therapy (iADT), for patients with castration sensitive biochemical progressive prostate cancer.

The main objectives are:

* Assess the feasibility of the study population and enrollment.
* Evaluate time to PSA relapse with nutritional intervention on iADT.

Participants who are receiving iADT will be dispensed Metformin and turmeric and complete a pill diary. Participants will also have blood and stool samples collected and complete quality of life questionnaires.

The long-term goal is to further assess the efficacy and safety of this nutritional regimen and the roles of metabolic syndrome, microenvironment/microbiome, and genomic vs epigenomic profiles in the care of these patients through a clinical trial.

Detailed description: The purpose of this research is to determine if a nutritional plan of metformin and turmeric is feasible for individuals receiving iADT for prostate cancer. Turmeric is an over-the-counter supplement that is believed to provide anti-inflammatory effects. Metformin is an FDA-approved medication for diabetes to help lower blood sugar. This feasibility study will be conducted according to the standard of care (SoC) for eligible subjects receiving iADT but coordinated and streamlined in a prospective manner to care for subjects while collecting and annotating data for the duration of their care.

All subjects will receive iADT + turmeric + metformin + dietary consultation.

SoC laboratory tests will be performed in accordance with clinical practice for the care of patients with prostate cancer on or off iADT. Additional vials of blood will be collected for research purposes in order to assess epigenetic biomarkers, CSC biomarkers, and cancer dormancy biomarkers. Stool samples will be used to obtain microbiome profiles. QOL instruments (FACT-P and AMS) will also be administered.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older.
* History of prior prostatectomy and/or radiation therapy to the prostate.
* Currently have rising PSA levels ≥ 0.2 ng/ml if they have undergone radical prostatectomy, or a PSA ≥ nadir + 2 if they have received only radiotherapy. Patients who were not offered salvage radiotherapy as an alternative treatment will be considered ineligible (due to a high PSA, other medical concerns).
* Currently have at least 2 consecutively rising serum PSA levels more than 1 week apart
* Currently have a PSA doubling time \< 9 months obtained within 60 days of consent.
* Eugonad with testosterone \> 150 ng/dl at time of consent.
* Prior ADT (including iADT) for up to 24 months in association with definitive treatment is permitted if completed at least 12 months prior to consent.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
* Willing to take study agents at the dose specified with meals.
* Willing to discontinue current vitamin/mineral supplements and use only those provided by study. Herbal supplements may still be used.

Exclusion Criteria:

* Current Chronic Lymphocytic Leukemia (CLL), Monoclonal Gammopathy of Unknown Significance (MGUS), Renal Cell Carcinoma (RCC) or another cancer requiring active treatment. Indolent or stable malignancies such as non-melanoma skin cancers are allowed.
* Any active or deteriorating liver or renal disease, Human Immunodeficiency Virus (HIV), Hepatitis B, Hepatitis C or bone marrow deficiency.
* Any history of allergic reactions attributed to turmeric, metformin, or other compounds of similar chemical or biologic compositions.
* History of lactic acidosis or risk factors for lactic acidosis (e.g., renal impairment, concomitant use of carbonic anhydrase inhibitors such as topiramate, hypoxic states such as acute congestive heart failure, excessive alcohol intake, and hepatic impairment).
* Any other condition that, in the opinion of the investigator, might interfere with the safe conduct of the study.

Primary outcomes:
measure: Assess feasibility of recruitment
timeFrame: 12 months of enrollment being open
measure: Evaluate time to PSA relapse with nutritional intervention on iADT.
timeFrame: up to 27 months
Secondary outcomes:
measure: Quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P), Version 4.
timeFrame: up to 27 months
measure: Quality of Life (QOL) assessed by the Aging Male Symptoms Questionnaire (AMS Questionnaire).
timeFrame: up to 27 months
Other outcomes:
measure: Expression levels of Metabolomic biomarkers from blood samples
timeFrame: up to 16 months
measure: Expression levels of CSC biomarkers including EMT and miRNAS from blood samples
timeFrame: up to 16 months
measure: Expression levels of Cancer dormancy Biomarkers (miR-200s, TGF-beta, BMPs, immune and inflammatory factors) from blood samples
timeFrame: up to 16 months
measure: Microbiome profiling from the stool samples to assess gut microbiome
timeFrame: up to 16 months
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Shi-Ming Tu, MD
role: PRINCIPAL_INVESTIGATOR
References: