Clinical trial NCT00765479: Soy Protein in Preventing Recurrent Cancer in Patients Who Have Undergone Surgery for Stage II Prostate Cancer
Official title: Randomized Placebo-Controlled Adjuvant Study of Prevention of Prostate Cancer Recurrence After Radical Prostatectomy by Soy Protein Isolate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Prostate Cancer
Keywords: stage IIB prostate cancer
stage IIA prostate cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-10-03
Enrollment: 284
Sex: MALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Soy protein may help prevent prostate cancer recurrence in patients who have undergone surgery for prostate cancer.

PURPOSE: This randomized phase II/III trial is studying how well soy protein works and compares it to a placebo in preventing recurrent cancer in patients who have undergone surgery for stage II prostate cancer.

Detailed description: OBJECTIVES:

* Determine whether soy protein isolate reduces the PSA failure rate and time to PSA failure within 2 years following radical prostatectomy in patients who are at high risk for prostate cancer recurrence.
* Determine the effects of soy protein isolate on intermediate biomarkers of steroid hormone axis (testosterone, estradiol, and SHBG) and thyroid activity (T3 and T4).
* Determine the effects of soy protein isolate on intermediate biomarkers of apoptosis (soluble Fas and Fas-ligand), angiogenesis (VEGF and bFGF), antioxidant activity (8-isoprostanes), and IGF axis (IGF-1 and IGFBP-3).
* Compare patients who are equol producers to those who are non-producers.

OUTLINE: This is a multicenter study. Patients are stratified according to hospital/clinic site (NYU vs UIC or Jesse Brown VA Medical Center vs other sites), number of high-risk characteristics (1 vs \> 1), and race (African American vs non-African American \[i.e., non-Hispanic White, Hispanic, Asian, and other\]). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive an oral soy protein isolate beverage once daily.
* Arm II: Patients receive an oral casein placebo beverage once daily. Treatment in both arms continues for up to 2 years in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for biomarker laboratory studies. Samples are analyzed to measure PSA levels by Tosoh PSA assay; cholesterol levels; isoflavone and equol concentrations by HPLC and ESA; and indicators of steroid hormone axis (testosterone, estradiol, and SHBG), indicators of thyroid activity (T3 and T4), indicators of apoptosis (soluble Fas and Fas-ligand), indicators of angiogenesis (VEGF and bFGF), indicators of oxidative stress (8-isoprostanes), and indicators of IGF axis (IGF-1 and IGFBP-3) by ELISA.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of prostate cancer

  * Clinically localized (T1c or T2) disease
* At high risk for recurrence, as defined by ≥ 1 of the following:

  * Preoperative PSA \> 20.0 ng/mL
  * Seminal vesicle invasion
  * Extracapsular extension (excluding the bladder neck)
  * Positive surgical margins (excluding apical margins)
  * Micrometastases in any removed pelvic lymph nodes
  * Final Gleason score of ≥ 8
* Must have undergone radical prostatectomy for prostate cancer within the past 4 months
* Must have an undetectable PSA (\< 0.07 ng/mL) at baseline, as measured by Tosoh PSA assay
* No clinical evidence of locally recurrent or metastatic disease

PATIENT CHARACTERISTICS:

* No significant intake of soy (i.e., more than once a week) at baseline including, but not limited to, any of the following:

  * Vegetarians who regularly consume soy products (e.g., tofu)
  * Individuals with customary Asian dietary habits, including regular intake of soy products
  * Individuals who use soy-based milk replacements
* No anemia, iron deficiency problems, or subclinical iron deficiency at baseline
* No diabetes
* No thyroid disease
* No requirement for a sodium-free diet
* No substantive tendency to be constipated (i.e., ≥ grade 2 constipation experienced regularly)
* No medical problem that would preclude the consumption of the soy containing beverage powder, including allergies against soy (or milk protein)
* No concurrent major disease, including major mental disease or major substance abuse problems
* No significant side effects from medication

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No concurrent radiotherapy or hormonal therapy
* No other concurrent adjuvant therapy for prostate cancer

Primary outcomes:
measure: Two-year PSA failure rate (as surrogate for recurrence)
measure: Time to PSA failure
Secondary outcomes:
measure: Isoflavone uptake or compliance as measured by serum isoflavone concentration
measure: Serum total cholesterol levels
measure: Steroid hormone axis as measured by serum testosterone, estradiol, and SHBG levels
measure: Thyroid activity as measured by serum T3 and T4 levels
measure: Apoptotic activity as measured by serum soluble Fas and Fas-ligand levels
measure: Angiogenesis as measured by serum VEGF and bFGF levels
measure: Oxidative stress as measured by serum 8-isoprostane levels
measure: IGF axis as measured by serum IGF-1 and IGFBP-3 levels
measure: Equol production as measured by serum equol concentration
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Maarten C. Bosland, DVSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Illinois at Chicago
name: Roohollah Sharifi, MD
References:
citation: Bosland MC, Enk E, Schmoll J, Schlicht MJ, Randolph C, Deaton RJ, Xie H, Zeleniuch-Jacquotte A, Kato I. Soy protein supplementation in men following radical prostatectomy: a 2-year randomized, placebo-controlled clinical trial. Am J Clin Nutr. 2021 Apr 6;113(4):821-831. doi: 10.1093/ajcn/nqaa390.
citation: Bosland MC, Huang J, Schlicht MJ, Enk E, Xie H, Kato I. Impact of 18-Month Soy Protein Supplementation on Steroid Hormones and Serum Biomarkers of Angiogenesis, Apoptosis, and the Growth Hormone/IGF-1 Axis: Results of a Randomized, Placebo-Controlled Trial in Males Following Prostatectomy. Nutr Cancer. 2022;74(1):110-121. doi: 10.1080/01635581.2020.1870706. Epub 2021 Jan 12.
citation: Bosland MC, Kato I, Zeleniuch-Jacquotte A, Schmoll J, Enk Rueter E, Melamed J, Kong MX, Macias V, Kajdacsy-Balla A, Lumey LH, Xie H, Gao W, Walden P, Lepor H, Taneja SS, Randolph C, Schlicht MJ, Meserve-Watanabe H, Deaton RJ, Davies JA. Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: a randomized trial. JAMA. 2013 Jul 10;310(2):170-8. doi: 10.1001/jama.2013.7842.