COAST Therapy in Advanced Solid Tumors and Prostate Cancer (COAST)

May 11, 2026 updated by: Medical University of South Carolina

Combination of Autophagy Selective Therapeutics (COAST) in Advanced Solid Tumors or Relapsed Prostate Cancer, A Phase I/II 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Phase I/II safety and efficacy study of COAST therapy in patients with advanced cancer for which no satisfactory therapy options exist. An initial Phase I cohort of 18-30 patients with advanced cancer will receive increasing components of the COAST regimen following a traditional 3+3 escalation design. The starting COAST combination includes hydroxychloroquine, sirolimus and metformin (DL1 - base combination). If this three-drug base combination is cleared for safety, two dose levels will be opened for enrollment exploring the safety of the base in combination with either dasatinib or nelfinavir. Patients will be assigned sequentially to DL2A (base + dasatinib) and DL2B (base + nelfinavir). If nelfinavir is deemed unsafe in combination with the base (DL2B is not cleared for safety, regardless of the safety of DL2A), no further drug combinations will be explored since all remaining combinations include nelfinavir. If both dasatinib and nelfinavir are individually safe in combination with the base (DL2A and DL2B are both cleared for safety), two additional dose levels will be explored, the first combining all five drugs and the second exploring nelfinavir at a higher dose. If dasatinib is not safe but nelfinavir is safe in combination with the base (DL2A but not DL2B cleared for safety), then only one additional dose level will be explored combining the base with a higher dose of nelfinavir. If neither DL2A nor DL2B are cleared for safety, then only the base combination may be considered safe. Once a given dose level is cleared for initial DLT evaluation (e.g., 0 of 3 patients have a DLT or at most 1 of 6 have a DLT), additional patients may be enrolled (i.e., 'backfilled') to that dose level while a higher dose level is being evaluated for safety. Prioritization for backfill will be given to dose levels proximal to the current dose level being explored, and to those dose levels with evidence of anti-tumor activity. Backfill patients who are DLT-evaluable will be included in making decisions on dose escalation. Accrual to a dose-level may be halted and additional patients enrolled to a lower dose level that was previously cleared for safety depending on the total number of DLTs observed among all DLT-evaluable patients at that lower dose level (initial and backfill patients). The maximum tolerated mixture is the highest dose level at which at most 1 of 6 patients experiences a DLT or, for a dose level sample size >6 due to additional backfill patients, the highest dose level at which the observed DLT rate is ≤16.7%. The recommended phase 2 dose (RP2D) will be determined based on the totality of data, including the maximum tolerated mixture, dose adjustments, all safety data including any DLT-equivalent events (safety events that meet the criteria for a DLT regardless of treatment cycle and trial phase), and any response data. The study team may recommend a dose level lower than the maximum tolerated mixture as the RP2D based on their review of the data in aggregate. However, the RP2D will not exceed the dose level corresponding to the maximum tolerated mixture. The phase II efficacy trial will evaluate the anti-tumor activity of the COAST RP2D combination in patients with advanced prostate cancer based on a Simon two stage optimum design. The primary endpoint is the16-week PSA progression-free rate following treatment initiation, where PSA progression is defined per PCWG3. A maximum of 29 patients will be enrolled. In the first stage, 10 patients will be accrued. If none of the first 10 patients are PSA progression-free at 16 weeks, we will halt registration. If one or more patients are PSA progression-free at 16 weeks, an additional 19 patients will be enrolled. If 4 or more out of the 29 patients are PSA progression-free at 16 weeks, the treatment will be declared promising. This study is powered at 80% with a one-sided type I error rate of 5%. Specifically, this study has an 80% chance of declaring promise if the true 16-week PSA progression-free rate is at least 20%. If instead the true 16-week PSA progression-free rate is at most 5%, then the study has a 5% chance of declaring promise and a 60% chance of early termination. Phase I patients treated at the RP2D who meet inclusion and exclusion criteria for phase II will be included in the phase II cohort. Treatment will continue until there is 1) unacceptable toxicity (grade 3 or 4 toxicity that does not resolve to grade 1 or less by 28 days after drug withdrawal), 2) institution of new additional cancer therapy, 3) withdrawal of consent, 4) any condition that, in the opinion of the treating physician, renders continued COAST treatment to not be in the patient's best interest, 5) lack of compliance with study procedures by the patient, or 6) PSA progression by 16 weeks of COAST therapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
76

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • Brian Orr, MD
        • Sub-Investigator:
          • Joseph Delaney, PhD
        • Sub-Investigator:
          • Michael B Lilly, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patient must have advanced solid tumor cancer of any type (Phase I) or advanced prostate cancer (Phase II). Prostate cancer patients must have a PSA of at least 0.1 ng/mL.
  2. Tissue diagnosis documented by pathology report, or clinic note attesting to same.
  3. Measurable / evaluable tumor by RECIST, quantitative blood biomarker, or radionuclide imaging
  4. Voluntary, signed and dated, Institutional Review Board (IRB) approved consent form in accordance with regulatory and institutional guidelines.
  5. Documented progression of disease during treatment with one or more standard systemic regimens. Single or multiple regimens of chemotherapy, hormone suppression therapy, radiation therapy, surgery, immunotherapy, or adoptive cell therapy are allowed.
  6. 18 years of age or older.
  7. ECOG performance status of 0-2.
  8. Bilirubin ≤ 1.5 times upper limit of normal (ULN) and AST / ALT ≤ 3 times ULN. Subjects with Gilbert's syndrome may be included if the total bilirubin is < 3 times ULN and the direct bilirubin is within normal limits.
  9. Serum creatinine ≤ 1.5 times ULN.
  10. Absolute neutrophil count (ANC) ≥ 1,000 cells / mm3
  11. Platelet count ≥ 75,000 cells / mm3
  12. Hemoglobin ≥ 9 g/ dL.
  13. Fasting glucose ≤ 160 mg/dL or non-fasting glucose ≤ 200 mg/dL.
  14. Urinalysis with no clinically significant abnormalities.
  15. Adequately controlled blood pressure as determined by the treating investigator.
  16. Subjects with the potential to produce children must agree to effective contraceptive method use during study participation.
  17. Patients requiring narcotic analgesics must be on stable doses for at least 2 weeks prior to study entry.
  18. Patients being considered for a dose level containing nelfinavir mesylate must discontinue any statin use within 48 hours of beginning study treatment.

Exclusion Criteria:

  1. New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or history of ischemia on ECG.
  2. Underlying psychiatric disorder requiring hospitalization within the last two years.
  3. Clinically significant neurological disorder (Parkinson's disease, dementia, multiple sclerosis), as determined by the enrolling investigator.
  4. Active, uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.
  5. Treatment with local or systemic radiation therapy, surgery, or investigational therapy within 28 days prior to registration.
  6. Unwillingness or inability to comply with procedures required in this protocol.
  7. Serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator.
  8. Patients who are receiving, coumadin, apixaban, argatroban or rivaroxaban.
  9. Patients who are currently participating in any other clinical trial of an investigational product.
  10. Any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator.
  11. Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose level 1
Combination product: Hydroxychloroquine, Metformin, Sirolimus
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily
Experimental: Dose level 4
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir, Dasatinib
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 1250mg twice daily Dasatanib 20mg daily
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir, Dasatinib
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 2500mg twice daily Dasatanib 20mg daily
Experimental: Dose level 2a
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Dasatanib
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Dasatinib 20mg daily
Experimental: Dose level 2b
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 1250mg twice daily
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 2500mg twice daily
Experimental: Dose level 3a
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir, Dasatinib
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 1250mg twice daily Dasatanib 20mg daily
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir, Dasatinib
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 2500mg twice daily Dasatanib 20mg daily
Experimental: Dose level 3b
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 1250mg twice daily
Combination product: Hydroxychloroquine, Metformin, Sirolimus, Nelfinavir
Hydroxychloroquine 600mg twice daily Metformin 500mg daily for 7 days, then increase to 1000mg daily Sirolimus 0.5mg daily Nelfinavir 2500mg twice daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) - Phase I
Time Frame: Minimum of 3 months after start of treatment on each dose level
Maximum dose achievable without dose limiting toxicities (DLT's)
Minimum of 3 months after start of treatment on each dose level
Measure of proportion of patients with disease control - Phase II
Time Frame: Minimum of 16 weeks after start of treatment, per patient
Stable disease by RECIST or PCWG3 criteria after 16 weeks of treatment on study.
Minimum of 16 weeks after start of treatment, per patient

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Quality of Life (QOL) score
Time Frame: Minimum of 16 weeks of treatment on study
To document the change in QOL (via disease-specific FACT questionnaire, composite score) in patients treated with COAST) after two and four cycles of treatment
Minimum of 16 weeks of treatment on study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of South Carolina

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 3, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 21, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 21, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 103352

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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