Clinical trial NCT03646162: Study of VERU-944 to Ameliorate Hot Flashes in Men With Advanced Prostate Cancer
Official title: Randomized, Double-blind, Placebo Controlled, Dose Finding Phase 2 Study Comparing Oral Daily Dosing of VERU-944 to Ameliorate the Vasomotor Symptoms Resulting From ADT in Men With Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer Metastatic
Lead sponsor: Veru Inc.
Sponsor class: INDUSTRY
First posted: 2018-08-24
Enrollment: 93
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized, double-blind, placebo controlled, dose finding Phase 2 study comparing oral daily dosing of VERU-944 after a week of loading (daily dosing) with placebo to ameliorate the vasomotor symptoms resulting from androgen deprivation therapy in men with advanced prostate cancer

Detailed description: This study is a multicenter, randomized, double-blind, placebo controlled, dose finding study of VERU-944 to treat hot flashes (vasomotor symptoms) in men with advanced prostate cancer on ADT. The study will have four arms with 30 subjects per arm. The subjects participating in the study will have advanced prostate cancer and will be undergoing androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone (LHRH) therapy (agonist or antagonist) for at least the three months prior to randomization and be experiencing regular moderate to severe hot flashes while on ADT. Subjects will all continue to receive ADT and will be randomized to receive, for the first four days, a loading dose followed by daily doses of placebo or VERU-944 (10 mg, 50 mg or 100 mg) orally for a total period of 12 weeks.

Eligibility criteria: Inclusion Criteria

1. Be over 18 years of age;
2. Be able to communicate effectively with the study personnel;
3. Have histologically confirmed prostate cancer;
4. Have been treated with an LHRH agonist or LHRH antagonist for at least the 3 months prior to randomization;
5. Be continued on an LHRH agonist or LHRH antagonist throughout this study;
6. Have experienced hot flashes for at least one month prior to study entry;
7. Have moderate or severe vasomotor symptoms (hot flashes) (defined as a minimum of 4 moderate to severe hot flashes per day or 12 per week at baseline);
8. ECOG performance status of 0 to 2
9. Be willing to uses electronic data capture for the relevant medical events

   • Must be at least 80% compliant during the screening period
10. Subjects must agree to use acceptable methods of contraception:

    * If their female partners are pregnant or lactating, acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication must be used. Acceptable methods are: Condom used with spermicidal foam/gel/film/cream/suppository. If the subject has undergone surgical sterilization (vasectomy with documentation of azospermia), a condom with spermicidal foam/gel/film/cream/suppository should be used.
    * If the male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 6 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository \[i.e., barrier method of contraception\], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom used with spermicidal foam/gel/film/cream/suppository).
    * If the female partner has undergone documented tubal ligation (female sterilization), a barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used.
    * If the female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used.
11. Subject is willing to comply with the requirements of the protocol through the end of the study.

Exclusion Criteria

1. Have a serum total testosterone concentration \> 50 ng/dL at screening;
2. Known hypersensitivity or allergy to estrogen or estrogen like drugs;
3. Any disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk;
4. Subjects with a personal history of abnormal blood clotting or thrombotic disease, including venous or arterial thrombotic events such as a history of stroke, deep vein thrombosis (DVT), and/or pulmonary embolus (PE);
5. Any subjects, as determined by a central laboratory, that have a:

   * Factor V Leiden gene mutation
   * Prothrombin gene mutation
6. Uncontrolled symptomatic congestive heart failure (NYHA Class III - IV), unstable angina pectoris, cardiac arrhythmia, or uncontrolled atrial fibrillation;
7. History of MI
8. The presence of consistently abnormal laboratory values which are considered clinically significant. In addition, any subject with liver enzymes (ALT or AST) above 2 times the upper limit of normal, total bilirubin above 2 times the upper limit of normal, or serum creatinine above 1.5 times the upper limit of normal will NOT be admitted to the study;
9. Received an investigational drug within a period of 90 days prior to enrollment in the study;
10. Received the study medication (VERU-944) previously;
11. Have previously taken within 6 months prior to screening or are currently taking diethylstilbestrol, other estrogens;
12. Currently taking gabapentin, estrogen, diethylstilbestrol, medroxyprogesterone acetate, clomiphene, selective serotonin reuptake inhibitors (SSRIs), other treatments for hot flashes
13. Recent hospitalization for more than 24 hours (within 30 days of screening);
14. Recent surgery (within 30 days of screening);
15. Have been previously diagnosed or treated for active cancer (other than prostate cancer or non-melanoma skin cancer) within the previous five years;
16. Have a BMI \>40.

Primary outcomes:
measure: Change in Frequency of Moderate to Severe Hot Flashes at 6 Weeks
timeFrame: 6 weeks
Secondary outcomes:
measure: Percentage Change in Severity of Moderate to Severe Hot Flashes at 6 Weeks
timeFrame: 6 weeks
measure: Change of Frequency of Moderate to Severe Hot Flashes at Week 12
timeFrame: Weeks 12
measure: Change in Severity of Moderate to Severe Hot Flashes at Week 12
timeFrame: Week 12
measure: Change in Bone Turnover Markers C-telopeptide (CTX)
timeFrame: 84 days
measure: Change in Bone Turnover Markers Alkaline Phosphatase
timeFrame: 84 days
Other outcomes:
measure: Change in Serum PSA
timeFrame: 84 Days
measure: Change in Serum Total Testosterone
timeFrame: 84 Days
measure: Change in Serum Free Testosterone
timeFrame: 84 days
measure: Change in Serum SHBG
timeFrame: 84 days
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)Sess Safety
timeFrame: 114 days
Locations:
city: Glendale
country: United States
facility: Gen1 Research
state: Arizona
city: Los Angeles
country: United States
facility: Tower Urology
state: California
city: San Bernardino
country: United States
facility: Urology of San Bernardino
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Golden
country: United States
facility: Foothills Urology
state: Colorado
city: Doral
country: United States
facility: Universal Axon Clinical Research
state: Florida
city: Miami
country: United States
facility: Medical Research Center
state: Florida
city: Coeur d'Alene
country: United States
facility: North Idaho Urology
state: Idaho
city: Jeffersonville
country: United States
facility: First Urology
state: Indiana
city: Shreveport
country: United States
facility: Regional Urology LLC
state: Louisiana
city: Towson
country: United States
facility: Chesapeake Urology
state: Maryland
city: Brick
country: United States
facility: Coastal Urology
state: New Jersey
city: Edison
country: United States
facility: Premier Urology Group
state: New Jersey
city: Elmont
country: United States
facility: Advance Urology
state: New York
city: Garden City
country: United States
facility: AccuMed Research
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals
state: New York
city: Middleburg Heights
country: United States
facility: Clinical Research Solutions
state: Ohio
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: Urology Clinics of North Texas
state: Texas
city: Houston
country: United States
facility: Houston Urology Partners
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio
state: Texas
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
Study officials:
affiliation: Veru Inc.
name: Barnette
role: STUDY_CHAIR
References: