COAST Therapy for Prostate Cancer
(COAST Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Medical University of South Carolina
Must not be taking: Coumadin, Apixaban, others
Disqualifiers: Cardiac disease, Psychiatric disorder, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this Phase I/II study is to determine the safety and effectiveness of up to 5 study drugs used together for the treatment of solid tumor cancers. The drugs are hydroxychloroquine, metformin, sirolimus, dasatinib and nelfinavir and are given orally.
Will I have to stop taking my current medications?
The trial requires that patients stop using statins (cholesterol-lowering drugs) within 48 hours before starting the study treatment if they are taking nelfinavir mesylate. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.
What data supports the effectiveness of the COAST Therapy drugs for prostate cancer?
Research suggests that metformin, one of the drugs in the COAST Therapy, may improve survival in prostate cancer patients and has potential anticancer effects. It is also being tested in combination with standard treatments for high-risk prostate cancer.
12345Is Metformin safe for use in humans?
Metformin is considered a safe and well-tolerated treatment, commonly used for type 2 diabetes and being explored for prostate cancer treatment.
12467What makes the COAST Therapy drug unique for prostate cancer?
The COAST Therapy drug is unique because it combines multiple agents like Hydroxychloroquine, Metformin, Sirolimus, Dasatinib, and Nelfinavir, which are not typically used together for prostate cancer. This combination targets different pathways in cancer cells, potentially offering a novel approach compared to standard treatments like docetaxel-based therapies.
89101112Eligibility Criteria
Adults with advanced solid tumors or prostate cancer, who have tried standard treatments without success. They must be relatively healthy, with stable vital signs and organ function, not on certain blood thinners or statins, and willing to use contraception if they can have children.Inclusion Criteria
Platelet count ≥ 75,000 cells / mm3
I can take care of myself and am up and about more than half of the day.
Serum creatinine ≤ 1.5 times ULN
+15 more
Exclusion Criteria
I haven't had radiation, surgery, or experimental treatments in the last 28 days.
I am currently taking blood thinners like coumadin or apixaban.
I have a serious health condition that might affect the study's goals.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment Phase I
Phase I cohort receives increasing components of the COAST regimen following a traditional 3+3 escalation design to determine the maximum tolerated dose.
Minimum of 3 months
Regular visits for dose escalation and monitoring
Treatment Phase II
Phase II evaluates the anti-tumor activity of the COAST RP2D combination in patients with advanced prostate cancer.
16 weeks
Regular visits for treatment and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of PSA progression-free rate.
4 weeks
Participant Groups
The trial is testing a combination of five drugs: hydroxychloroquine, nelfinavir, metformin, dasatinib, and sirolimus for their safety and effectiveness in treating solid tumor cancers including advanced prostate cancer.
6Treatment groups
Experimental Treatment
Group I: Dose level 4Experimental Treatment1 Intervention
Group II: Dose level 3bExperimental Treatment1 Intervention
Group III: Dose level 3aExperimental Treatment1 Intervention
Group IV: Dose level 2bExperimental Treatment1 Intervention
Group V: Dose level 2aExperimental Treatment1 Intervention
Group VI: Dose level 1Experimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Medical University of South CarolinaCharleston, SC
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Who Is Running the Clinical Trial?
Medical University of South CarolinaLead Sponsor
References
Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform. [2021]Metformin is a safe, well-tolerated, inexpensive treatment that can be given in addition to current standard-of-care therapies for prostate cancer. Its use might mitigate the deleterious side effects of castration and exert an additional anticancer effect. It will be incorporated in the STAMPEDE trial platform in summer 2016. This will test its true utility as a repurposed treatment for men with high-risk locally advanced or metastatic prostate cancer at first presentation.
Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study. [2022]The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM).
The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia. [2018]We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis.
A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways. [2023]Metformin and phenformin, biguanide derivatives that are widely used to treat type 2 diabetes mellitus, have recently been shown to exert potential anticancer effects in prostate cancer. This study compared the antiprostate cancer effects of the novel biguanide derivative IM176 with those of metformin and phenformin.
Prostate Cancer-specific Survival After Radical Prostatectomy Is Improved Among Metformin Users but Not Among Other Antidiabetic Drug Users. [2022]Metformin has been linked to improved survival among diabetic prostate cancer (PCa) patients, while hyperinsulinemia and insulin usage has been related to worse prognosis.
STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway. [2023]Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten-null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa.
Tolerability, safety and pharmacokinetics of ridaforolimus in combination with bicalutamide in patients with asymptomatic, metastatic castration-resistant prostate cancer (CRPC). [2021]Recent data indicate that there is a significant cross-talk between the PI3K/Akt/mTOR and androgen receptor signaling pathways. We evaluated safety and tolerability as well as potential drug-drug interaction of ridaforolimus, a mammalian target of rapamycin (mTOR) inhibitor, when combined with the androgen receptor inhibitor bicalutamide in patients with asymptomatic, metastatic castration-resistant prostate cancer.
A phase I trial of docetaxel/estramustine/imatinib in patients with hormone-refractory prostate cancer. [2018]Docetaxel/estramustine was a commonly used regimen to treat metastatic hormone-refractory prostate cancer. Imatinib inhibits the platelet-derived growth factor receptor that is expressed in prostate cancer and is synergistic with taxanes in preclinical prostate cancer models.
A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone-refractory prostate cancer. [2013]A Phase II prospective trial was performed to study the efficacy of combination therapy with dexamethasone, calcitriol (1,25-dihydroxyvitamin D3), and carboplatin in patients with hormone-refractory prostate cancer (HRPC). Preclinical data from prostate cancer cell lines suggested a synergistic effect of these therapies.
Metformin Has Positive Therapeutic Effects in Colon Cancer and Lung Cancer. [2018]Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase. We investigated survival, recurrences and metastasis in patients with type 2 diabetes mellitus (DM2) along with colorectal cancer (CC) or lung cancer (LC) taking MF using the electronic medical record in Memphis Veterans Affairs Medical Center (colon, n = 202; lung, n = 180).
The current role of chemotherapy in metastatic hormone-refractory prostate cancer. [2022]Since the publication of the Southwest Oncology Group (SWOG) 99-16 and TAX 327 studies, which demonstrated a survival benefit for docetaxel-based therapy, clinicians for the first time have a therapy to offer men with metastatic prostate cancer that is not merely palliative in its effects. Phase 2 and phase 3 trials are now building on the findings of SWOG 99-16 and TAX 327 by evaluating the potential of combination taxane-based therapies, such as docetaxel plus high-dose calcitriol, docetaxel-estramustine-bevacizumab, and docetaxel-thalidomide. The optimal timing of docetaxel-based chemotherapy is still unknown, as there are no prospective clinical trial data to indicate whether earlier treatment (eg, at the time of prostate-specific antigen failure) is more or less effective than later treatment (eg, in metastatic and/or symptomatic disease).
Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer. [2018]To evaluate the safety and efficacy of combined docetaxel-zoledronic acid treatment in patients with metastatic hormone-refractory prostate cancer (HRPC), as bisphosphonates are reported have a synergistic antitumoral effect when combined with taxanes.