A Pilot Study to Enhance F18 FDG-PET Imaging of Prostate Cancers With the Metabolic Inhibitor Ranolazine

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Colorado, Denver
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01992016
First received: November 12, 2013
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

This pilot clinical trial studies fludeoxyglucose F18 (FDG)-positron emission tomography (PET) in imaging patients with prostate cancer treated with ranolazine. Diagnostic procedures, such as FDG-PET, may help find prostate cancer and find out how far the disease has spread. Giving ranolazine may enhance FDG-PET imaging by increasing the amount of glucose available for uptake by the scan.


Condition Intervention
Adenocarcinoma of the Prostate
Bone Metastases
Soft Tissue Metastases
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Stage IV Prostate Cancer
Drug: Ranolazine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Pilot Study to Enhance F18 FDG-PET Imaging of Prostate Cancers With the Metabolic Inhibitor Ranolazine

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Rate of successful enhancement of FDG-PET imaging [ Time Frame: Within 1 week after completion of ranolazine treatment ] [ Designated as safety issue: No ]
    The proportion of success and its exact 90% confidence limits will be reported for each of the two arms.


Secondary Outcome Measures:
  • Quantitative change in FDG-PET imaging [ Time Frame: Within 1 week after completion of ranolazine treatment ] [ Designated as safety issue: No ]
    T-test or logistic regression will be used to assess if there is any difference in tumor size between the enhanced and not enhanced imagining. Logistic regression will be used to evaluate if tumor size is associated with the outcome. Effect size (from t-test) and odds ratio (from logistic regression) will be reported. Successful enhancement rate for each tumor location will be summarized.

  • Rate of successful enhancement of FDG-PET imaging [ Time Frame: Within 1 week after completion of ranolazine treatment ] [ Designated as safety issue: No ]
    The proportion of success and its exact 90% confidence limits will be reported for each of the two arms.

  • Quantitative change in PET imaging signal [ Time Frame: Within 1 week after completion of ranolazine treatment ] [ Designated as safety issue: No ]
    The proportion of success and its exact 90% confidence limits will be reported for each of the two arms.


Estimated Enrollment: 40
Study Start Date: November 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (localized prostate cancer)
Patients receive ranolazine PO BID for 5 days. Patients undergo FDG-PET/CT scan at baseline and after ranolazine treatment. Patients may then undergo robotic or open radical prostatectomy.
Drug: Ranolazine
1000mg given orally twice daily for 5 days
Other Name: Ranexa
Experimental: Arm II (metastatic prostate cancer)
Patients receive ranolazine and undergo FDG-PET/CT as in Arm I.
Drug: Ranolazine
1000mg given orally twice daily for 5 days
Other Name: Ranexa

Detailed Description:

PET scans have traditionally not been very good at detecting prostate cancers. This is because prostate cancer cells do not take up glucose well so the signals are very weak. The ability of PET imaging to detect cancers requires that the cancer cells take up glucose into the cells. Different methods are being tested to see if we can improve the detection of prostate cancers using PET scans.

Ranolazine is a drug that is already approved by the FDA for treatment of chronic chest pain in people with heart disease. Ranolazine has been studied in the laboratories at the University of Colorado Denver, Anschutz Medical Campus. Ranolazine has been added to prostate cancer cells and grown in petri dishes and in animals in the laboratory. It has been shown to increase the glucose uptake of prostate cancer cells. The goal of this study is to see if patients taking ranolazine will have better PET imaging of their prostate cancers.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent has been obtained.
  2. Adults over 18 years of age.
  3. Histological or cytologically confirmed prostate adenocarcinoma.
  4. Arm 1 patients must have treatment-naïve, Gleason ≥ 7 prostate cancer based on transrectal ultrasound (TRUS) biopsy, have localized disease, and have decided to undergo radical prostatectomy (open or robotic) as definitive treatment for their prostate cancer.
  5. Arm 2 patients must have lymph node, soft tissue, bone, or visceral metastatic disease measuring ≥ 1 cm (lytic component if bone), documented by either CT or MRI imaging within 6 weeks of signing consent. Arm 2 patients may have hormone-sensitive or castrate-resistant disease and may be receiving treatment with hormonal therapies.
  6. For Arm 1 patients, the time from the TRUS prostate biopsy to the planned first study PET scan must be ≥ 1 month. For patients who have undergone prior prostate mapping biopsy, the time from the mapping biopsy to the planned first study PET scan must be ≥ 2 months.
  7. For Arm 1 patients, participation in this study, in the opinion of the treating physicians, will not introduce delays in surgery that would adversely affect the patient.
  8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  9. Fasting blood glucose ≤ 120 mg/dL.
  10. Adequate renal function (Creatinine ≤ 1.5 X ULN)
  11. Adequate hepatic function (bilirubin < 1.5 X upper limit of normal (ULN), alanine aminotransferase (ALT) < 1.5 X ULN, aspartate aminotransferase (AST) < 1.5 X ULN, and albumin ≥ 3 g/dL. For patients with known bone metastases, alkaline phosphatase < 5 X ULN is acceptable.
  12. Must be able to take oral medication without crushing, dissolving or chewing tablets.
  13. Written authorization for use and release of health and research study information has been obtained.
  14. Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection during the study and for 1 week after the last dose of ranolazine.

Exclusion Criteria:

  1. Have small cell carcinoma or neuroendocrine component >50%.
  2. Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of ranolazine.
  3. Documented hypersensitivity to any component of ranolazine (Ranexa®) pills.
  4. Need for medications that are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir), moderate CYP3A inhibitors (e.g. diltiazem, verapamil, erythromycin, fluconazole, grapefruit juice or grapefruit-containing products), CYP3A inducers (e.g. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's wort), CYP3A substrates with a narrow therapeutic range (e.g. cyclosporine, tacrolimus, sirolimus), P-gp inhibitors or substrates (e.g. cyclosporine, digoxin), polypeptide 6 (CYP2D6) substrates (e.g. tricyclic antidepressants and antipsychotics),or simvastatin at doses > 20 mg/day.
  5. Have corrected QT interval (QTc)> 450 msec (male) or > 470 msec (female) on 12-lead electrocardiogram.
  6. Poorly controlled diabetes, hemoglobin A1c (Hgb A1C) >9 or random blood glucose >250mg/dL).
  7. Active or symptomatic viral hepatitis or chronic liver disease.
  8. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class III-IV heart disease or cardiac ejection fraction measurement of <50%.
  9. Active infection requiring antibiotics.
  10. Major surgery or radiation treatment within 3 months.
  11. Cytotoxic chemotherapy within 4 weeks.
  12. Immunotherapy within 6 months.
  13. Any prior therapy with Radium-223, Samarium, or Strontium.
  14. Arm 1 patients may not have received any prior luteinizing-hormone-releasing hormone (LHRH) agonists/antagonists, anti-androgens, or chemotherapy for their prostate cancer. 5-alpha reductase inhibitors (finasteride, dutasteride) may be allowed.
  15. Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01992016

Contacts
Contact: Michael Wacker 720-848-3427 michael.wacker@ucdenver.edu

Locations
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Michael Wacker    720-848-3427    michael.wacker@ucdenver.edu   
Principal Investigator: Elaine Lam, MD         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Elaine Lam, MD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01992016     History of Changes
Other Study ID Numbers: 13-1908.cc, NCI-2013-02000
Study First Received: November 12, 2013
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Prostate cancer
F18 FDG-PET
Imaging
Ranolazine
Bone metastases
Soft tissue metastases

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Neoplasm Metastasis
Neoplasms, Second Primary
Bone Neoplasms
Bone Marrow Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014