Hot Flashes, Prostate Cancer
Conditions
Keywords
recurrent prostate cancer, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, stage IV prostate cancer, hot flashes
Brief summary
RATIONALE: Soy protein/isoflavones and venlafaxine may help relieve hot flashes in patients receiving hormone therapy for prostate cancer. It is not yet known whether soy protein/isoflavones are more effective than venlafaxine when given together or with a placebo in treating hot flashes. PURPOSE: This randomized phase III trial is studying soy protein/isoflavones and venlafaxine to compare how well they work when given together or with a placebo in treating hot flashes in patients receiving hormone therapy for prostate cancer.
Detailed description
OBJECTIVES: Primary * Assess the effect of soy protein/isoflavones and venlafaxine on the hot flash symptom severity score in patients undergoing hormonal manipulation for treatment of prostate cancer. Secondary * Assess the effect of soy protein/isoflavones and venlafaxine on quality of life of these patients. * Monitor and assess the participant drop out rate. OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to severity of disease (metastatic vs nonmetastatic) and baseline severity of hot flashes. Patients are randomized to 1 of 4 treatment arms. * Arm I: Patients receive oral placebo pill and oral soy protein/isoflavones powder once daily. * Arm II: Patients receive oral venlafaxine and oral placebo powder once daily. * Arm III: Patients receive oral venlafaxine and oral soy protein/isoflavones powder once daily. * Arm IV: Patients receive oral placebo pill and oral placebo powder once daily. Treatment in all arms continues for 12 weeks in the absence of disease progression or unacceptable toxicity. After 12 weeks of treatment, patients in arms I and III receive a tapered dose of oral venlafaxine once daily for 1 week. Patients complete a vasomotor symptom diary once daily beginning 7 days before the initiation of study treatment and continuing until the completion of study treatment. Quality of life is assessed at baseline and at week 12. PROJECTED ACCRUAL: A total of 176 patients will be accrued for this study.
Interventions
DIETARY_SUPPLEMENToral soy protein/isoflavones powder
Soy protein powder (20gm) orally 160 mg of total isoflavones isocaloric supplement of casein protein
DRUGVenlafaxine
Patients receive oral venlafaxine 75mg.
DIETARY_SUPPLEMENTPlacebo Powder
Placebo powder (20gm casein protein) orally 0 mg of total isoflavones
DRUGPlacebo Pill
Patients receive oral placebo pill.
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic documentation of prostate cancer, any stage Life expectancy of \> nine months * Prior or current androgen deprivation for treatment or control of prostate cancer to include: * Bilateral Orchiectomy * LHRH agonist (with or without antiandrogen therapy) ie: leuprolide (Lupron), goserelin (Zoladex), bicalutamide (Casodex), flutamide (Eulexin), or similar agents * Chemotherapy * Radiation (Patients may undergo concurrent radiation therapy to the prostate, prostate + seminal vesicles, and/or pelvis). Seed implants are allowed * Participant report of hot flash frequency of an average of four or more per day, as defined by sweating, flushing, sensation of warmth, night sweats (Average of 28 per week) * Hot flashes must be moderate or severe (See appendix A for hot flash definitions) * Grade 2 (Moderate flashes) are warmer, produce obvious perspiration, and last 2 to 3 minutes * Grade 3 (Severe flashes) causes profuse perspiration, generate intense heat, last longer and interfere with ongoing activity * Age \>21 * No allergies to soy or dairy products * No current use of SSRIs, SNRI's, MAOIs, or Linezolide * No uncontrolled hypertension (160/90) or greater than Class I American Heart Association functional capacity * No history of mania, hypomania, bipolar disorder, or anorexia nervosa * No history of seizures * No history of hepatic dysfunction) * Must have a telephone * Signed protocol-specific Informed Consent * Participants consuming soy foods or soy based supplements must continue on a stable regimen during study participation * Patients should maintain same treatment and medications for prostate cancer throughout entire study. * No change in treatment for 2 weeks prior to registration. * Current use of medications and herbal supplements for hot flashes are allowed if on a stable regimen throughout the entire study. (Does not include anti-depressants)
Exclusion criteria
* Anticipated changes in prostate cancer treatment plan (i.e., hormonal manipulation, changes in chemotherapy) * Concurrent antidepressant therapy * History of intolerance to venlafaxine * Recent (within 14 days) use of venlafaxine (Effexor XRTM), monoamine oxidase inhibitor, SSRI (selective serotonin reuptake inhibitor), or SNRI (selective norepinephrine reuptake inhibitor) * History of seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hot Flash Symptom Severity Score | 12 weeks | The primary objective of this randomized trial is to assess the effect of soy and Venlafaxine on the hot flash symptom severity score in men undergoing hormonal manipulation for treatment of prostate cancer. Hot flash severity will be quantitated using the symptom diary (as the sum of the number of hot flashes (any number greater than or equal to 0) times their severity (0=none, 1=mild, 2=moderate, 3=severe)). The primary end point is the 12 week hot flash score relative to the baseline value (i.e., 100\*(12 week score)/baseline score). The range is 0 to infinity. Lower values represent a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life | 12 weeks | Quality of life is quantified by the Functional Assessment of Cancer Therapy - Prostate questionnaire (FACT-P). The FACT-P consists of four general subscales (functional, emotional, social, and physical) consisting of a total of 27 questions as well as a Prostate specific subscale consisting of 12 questions. Each question is answered on a 0 to 4 scale. The FACT-P score ranges from 0 to 156; higher scores denote better quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I - Placebo Patients receive oral placebo pill and oral placebo powder once daily. | 30 |
| Arm II - Soy Patients receive oral placebo pill and oral soy protein/isoflavones powder once daily. | 30 |
| Arm III - Venlafaxine Patients receive oral venlafaxine pill and oral placebo powder once daily. | 30 |
| Arm IV - Soy + Venlafaxine Patients receive oral venlafaxine pill and oral soy protein/isoflavones powder once daily. | 30 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 5 | 5 |
| Overall Study | Off/Toxicity | 3 | 7 | 5 | 5 |
Baseline characteristics
| Characteristic | Arm II - Soy | Arm III - Venlafaxine | Arm I - Placebo | Arm IV - Soy + Venlafaxine | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 18 Participants | 19 Participants | 19 Participants | 77 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 12 Participants | 11 Participants | 11 Participants | 43 Participants |
| Age, Continuous | 71.0 years STANDARD_DEVIATION 8.2 | 67.8 years STANDARD_DEVIATION 9.9 | 67.8 years STANDARD_DEVIATION 8.8 | 67.5 years STANDARD_DEVIATION 9.1 | 68.5 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 30 participants | 30 participants | 30 participants | 30 participants | 120 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 30 Participants | 30 Participants | 30 Participants | 30 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 30 | 23 / 27 | 29 / 29 | 27 / 28 |
| serious Total, serious adverse events | 4 / 30 | 5 / 27 | 5 / 29 | 5 / 28 |
Outcome results
Primary
Hot Flash Symptom Severity Score
The primary objective of this randomized trial is to assess the effect of soy and Venlafaxine on the hot flash symptom severity score in men undergoing hormonal manipulation for treatment of prostate cancer. Hot flash severity will be quantitated using the symptom diary (as the sum of the number of hot flashes (any number greater than or equal to 0) times their severity (0=none, 1=mild, 2=moderate, 3=severe)). The primary end point is the 12 week hot flash score relative to the baseline value (i.e., 100\*(12 week score)/baseline score). The range is 0 to infinity. Lower values represent a better outcome.
Time frame: 12 weeks
Population: All randomized participants were analyzed in a repeated measures mixed model. This allowed inclusion of all study participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Placebo | Hot Flash Symptom Severity Score | 52.3 percent of baseline score | Standard Error 10.8 |
| Arm II - Soy | Hot Flash Symptom Severity Score | 77.2 percent of baseline score | Standard Error 11.6 |
| Arm III - Venlafaxine | Hot Flash Symptom Severity Score | 68.9 percent of baseline score | Standard Error 12.1 |
| Arm IV - Soy + Venlafaxine | Hot Flash Symptom Severity Score | 73.8 percent of baseline score | Standard Error 11.9 |
Comparison: The null hypothesis was that there was no difference in the hot flash severity score at 12 weeks.p-value: 0.3455Mixed Models Analysis
Secondary
Quality of Life
Quality of life is quantified by the Functional Assessment of Cancer Therapy - Prostate questionnaire (FACT-P). The FACT-P consists of four general subscales (functional, emotional, social, and physical) consisting of a total of 27 questions as well as a Prostate specific subscale consisting of 12 questions. Each question is answered on a 0 to 4 scale. The FACT-P score ranges from 0 to 156; higher scores denote better quality of life.
Time frame: 12 weeks
Population: Participants with baseline and 12 week quality of life data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Placebo | Quality of Life | 115.6 units on a scale | Standard Error 2.4 |
| Arm II - Soy | Quality of Life | 121.5 units on a scale | Standard Error 2.5 |
| Arm III - Venlafaxine | Quality of Life | 114.3 units on a scale | Standard Error 2.7 |
| Arm IV - Soy + Venlafaxine | Quality of Life | 117.7 units on a scale | Standard Error 2.8 |
Comparison: Null hypothesis was that there was no difference in quality of life between the four groups at 12 weeks.p-value: 0.2081ANCOVA