Sipuleucel-T with or without Low-Protein Diet in Treating Patients with Metastatic Castration-Resistant Prostate Cancer
This randomized pilot phase II trial studies how well sipuleucel-T with or without low-protein diet works in treating patients with castration-resistant prostate cancer that has spread to other parts of the body (metastatic). Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Giving a low-protein diet may help sipuleucel-T work better than it does when giving with a standard protein-diet in treating patients with prostate cancer.
Inclusion Criteria
- Histologically documented adenocarcinoma of the prostate
- Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone scan and/or computed tomography (CT) scan of the chest, abdomen, and pelvis
- Castration resistant prostate cancer; subjects must have current or history of surgical or medical castration. Castration levels of testosterone (< 50 ng/dL) achieved via medical or surgical castration; surgical castration must have occurred at least 3 months prior to registration; subjects who are not surgically castrate must be receiving medical castration therapy, have initiated such therapy at least 3 months prior to registration, and continue such therapy until the time of confirmed objective disease progression
- Patients currently on non-steroidal antiandrogens (i.e. bicalutamide, abiraterone, enzalutamide etc.) have the choice of continuing the drug treatment or interrupting it
- Life expectancy of at least 6 months
- White blood cell (WBC) >= 2,500 cells/uL
- Absolute neutrophil count (ANC) >= 1,000 cells/uL
- Platelet count >= 100,000 cells/uL
- Hemoglobin (HgB) >= 9.0 g/dL
- Creatinine =< 2.0 mg/dL
- Total bilirubin =< 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (aspartate aminotransaminase [AST], serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
- Alanine aminotransferase (alanine aminotransaminase [ALT], serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN
Exclusion Criteria
- The presence of lung, liver, or known brain metastases, malignant pleural effusions, or malignant ascites
- Moderate or severe symptomatic metastatic disease; subjects who meet either of the following criteria must be excluded: * A requirement for treatment with opioid analgesics for any reason within 28 days prior to registration * Average weekly pain score of 4 or more as reported on the 10-point Visual Analog Scale (VAS) on the Registration Pain Log
- Eastern Cooperative Oncology Group (ECOG) performance status > 2
- Treatment with any of the following medications or interventions within 28 days of registration: * Systemic corticosteroids; however, use of inhaled, intranasal, and topical steroids is acceptable * Ketoconazole * High dose calcitriol [1,25(OH)2VitD] (i.e., > 7.0 ug/week) * Any other systemic therapy for prostate cancer (except for medical castration)
- Prior treatment with sipuleucel-T (on clinical trial or as part of standard of care)
- Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression
- Paget’s disease of bone
- A history of stage III or greater cancer, excluding prostate cancer; basal or squamous cell skin cancers must have been adequately treated and the subject must be disease-free at the time of registration; subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for >= 3 years at the time of registration
- A requirement for systemic immunosuppressive therapy for any reason
- Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 degrees Fahrenheit [F] or 38.1 degrees Celsius [C]) within 1 week prior to registration
- A known allergy, intolerance, or medical contraindication to receiving the contrast dye required for the protocol-specified CT imaging
- Any medical intervention or other condition which, in the opinion of the principal investigator, could compromise adherence with study requirements or otherwise compromise the study’s objectives
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03329742.
PRIMARY OBJECTIVE:
I. To assess the feasibility of low-protein diet intervention in patients with metastatic castrate-resistant prostate cancer (CRPC) receiving immunotherapy with sipuleucel-T.
SECONDARY OBJECTIVES:
I. To assess whether low-protein diet intervention augments the immune response to sipuleucel-T in men with metastatic CRPC.
II. To assess the safety and tolerability of the combination of sipuleucel-T and low-protein diet intervention.
III. To obtain preliminary evidence of clinical efficacy of the combination of sipuleucel-T and low-protein diet compared to sipuleucel-T and control-diet, including objective response rate (partial + complete response), progression-free survival (PFS) and overall survival (OS), and changes in prostate-specific antigen (PSA).
EXPLORATORY OBJECTIVES:
I. To assess the immune response at week 0, 6, 12, and 24 (weeks post first infusion) using the following testing: T cell immunity to prostatic acid phosphatase (PAP), T cell immunity to prostate antigen (PA)202, IgM and IgG antibodies to PAP and PA2024, C45 cells, effector CD4 T cells, effector CD8 T cells, foxP3+ CD4+ regulatory T cells, CD11b+ CD14+ HLA-DR low/neg myeloid-derived suppressor cell (MDSC), CD14+Dump-HLA-DR+.
II. To measure circulating tumor cells and compare numeration at week 0, 6, 12, and 24 (weeks post first infusion).
III. To assess nutritional status, hand grip strength, appetite, mood, stress, and quality of life at week 0, 3, and 6 (weeks post first infusion).
IV. To collect stool samples at week 0 and 6 for bacterial deoxyribonucleic acid (DNA) analysis.
V. To assess the change of lean body mass as assessed by full body dual X-ray absorptiometry (DXA) scan performed at baseline and at week 12 post diet intervention.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients consume a standard 20% protein diet on days -7 to +42. Patients also receive sipuleucel-T intravenously (IV) over 60 minutes on day 1. Treatment with sipuleucel-T repeats every 14 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients consume a low 10% protein diet on days -7 to +42. Patients also receive sipuleucel-T IV over 60 minutes on day 1. Treatment with sipuleucel-T repeats every 14 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at day 43, day 72, week 12, week 24, and then every 3-6 months.
Trial PhaseNo phase specified
Trial Typetreatment
Lead OrganizationIndiana University/Melvin and Bren Simon Cancer Center
Principal InvestigatorNabil Adra
- Primary IDIUSCC-0614
- Secondary IDsNCI-2018-00086
- ClinicalTrials.gov IDNCT03329742