A Study of Experimental Combination of Enzalutamide and Indomethacin For Recurrent or Metastatic Hormone-Resistant Prostate Cancer

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"This is a research study for patients with prostate cancer that has become resistant to first-line androgen deprivation therapy."
Age: 19 years or older
Gender:
Male
Healthy Volunteers: No
Keywords: Castration-Resistant Prostate Cancer, CRPC, prostate cancer
Type: Drug study, Phase [ 1 , 2]
Target:
38 Participants
Investigator:
Description
You are being asked to take part in this study because you have prostate cancer. Your cancer has become resistant to the first-line androgen deprivation therapy. We call this castration-resistant prostate cancer or CRPC. It has also become resistant to another FDA-approved medication abiraterone.

This study will determine if the combination of enzalutamide (a FDA-approved medication for CRPC) and indomethacin (a FDA-approved medication for pain) can improve the treatment outcome of CRPC. This will be compared to enzalutamide therapy alone.

Enzalutamide and indomethacin have been used in clinic but we have not studied them together. During the first stage, we will determine the dose and schedule of these two drugs. After we know the dose and schedule, the safety and efficacy of the combination of these drugs will be studied.

We will study the following to help us decide if the combination of enzalutamide and indomethacin is safe and effective:
- Your physical state
- Changes in the size of the tumor
- Laboratory tests
This study requires

If you decide to participate in this study and you meet all of the requirements to join the study, you will be asked to do the following:

Take indomethacin by mouth followed by a big glass of water. The dose of indomethacin is 50 to 100 mg once a day. Indomethacin should be taken with food. Always follow the instructions for use of indomethacin given to you by your study doctor. You should take indomethacin around the same time each day. You will also take four enzalutamide pills once a day by mouth (160 mg per day). It can be taken with or without food. This medication is not a study medication; it has been approved by the FDA. You will likely need to take this medication whether you participate in this study or not. Do not miss any tablets/capsules.

You will also be asked to complete a document called a pill diary. At the beginning of each cycle you will be given a pill diary. You will use the pill diary to track when you take your enzalutamide and indomethacin. At the end of each cycle you will be asked to return the completed and signed pill diary, your pill bottles and any remaining enzalutamide and indomethacin to your study doctor. If your study doctor feels it is necessary or if you experience severe side effects, enzalutamide and/or indomethacin may be stopped and then started again at a lower dose or may be stopped completely depending on the results of your laboratory tests. You may continue to be treated with indomethacin until your disease gets worse, you decide not to take part in the study any longer, or your doctor decides it is in your best interest to stop treatment.

Clinic visits will occur every 2 weeks during the first 8 weeks while on-study, and every 4 weeks from then on. At each visit, tell the study staff about any medications you are taking during the study. This includes prescriptions drugs, over-the- counter medicines and vitamins. This is very important. Please tell your study doctor or study staff if you have any unusual symptoms. You will be asked questions about your medical history and about any medications you are currently taking or have taken in the past. You will have a complete physical exam and your vital signs will be taken. You will be asked about your ability to perform every day activities. Up to 10 mL of blood will be taken (less than 1 tablespoon) for routine tests and will be collected every month. Repeat radiologic scans (an X-Ray and/or a CT and/or an MRI) will be taken every other month for the first four months, then every three months.

The study team will discuss the tests and procedures required in greater detail.

Who can participate

Inclusion criteria:

  • Patients must have histologically or cytologically confirmed prostate cancer (CaP); CaP can be recurrent disease after definitive therapy (radical prostatectomy or radiation therapy) for localized CaP, or metastatic CaP
  • Patients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):
  • Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug
  • Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)
  • Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measure
  • Measurable disease is not required
  • Patients who have measurable disease must have had X-rays, scans or physical examinations used for tumor measurement completed within 28 days prior to initial administration of drug
  • Patients must have non-measurable disease (such as nuclear medicine bone scans) and non-target lesions (such as PSA level) assessed within 28 days prior to initial administration of drug
  • Soft tissue disease that has been radiated within two months prior to registration is not assessable as measurable disease; soft tissue disease that has been radiated two or more months prior to registration is assessable as measurable disease provided that the lesion has progressed following radiation; as the biology of previously irradiated tumors may be different from non-irradiated tumors, patients must have at least one measurable lesion outside the previously irradiated region in order to be considered to have measurable disease
  • If PSA is the only indicator of disease and patients do not have any metastatic disease, PSA value must be 5.0 or higher
  • Patients must have been surgically or medically castrated; if the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists; serum testosterone must be at castration levels (< 50 ng/dL) within 3 months prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 6 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 1.5 x institutional upper limit of normal
  • Creatinine =< 1.5 x institutional upper limit of normal
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of enzalutamide administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents within the preceding 4 weeks
  • Patients on herbs or other alternative medicines for the treatment of prostate cancer, including but not limited to saw palmetto, PC-SPES
  • Patient has received enzalutamide or ketoconazole for the treatment of prostate cancer; however, previous treatment with other hormonal therapy (bicalutamide, abiraterone, flutamide, and nilutamide) or chemotherapy (docetaxel, cabazitaxel, or mitoxantrone) is allowed
  • Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin or other stage 0 or I cancers
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or indomethacin
  • 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
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Patients with an active bleeding diathesis
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol
  • Patients with symptomatic metastatic prostate cancer such as moderate to severe pain, impaired organ function, or spinal cord compression will be excluded from this study unless these issues have been taken care of
  • Patients with a history of seizure disorder, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation
  • Patients with a history of peptic ulcer disease or gastrointestinal bleeding
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
You will take part for as long as your cancer is not growing and you are not having any unmanageable side effects. After you finish taking indomethacin and enzalutamide, you will be asked to visit the office for at least one follow-up exam. After that, we will collect follow-up information about your cancer and any further treatment you receive.
Recruitment period
From Sept. 21, 2016
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Research Topic
Conditions:
  • Metastatic Prostate Carcinoma
  • Recurrent Prostate Carcinoma
  • Stage IV Prostate Cancer

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