Actively Recruiting
PROMIZE: Assessing Safety and Anti-Tumor Activity of Oral Antibiotic Combinations with Enzalutamide in Metastatic Castration-Resistant Prostate Cancer
Led by Institute of Cancer Research, United Kingdom · Updated on 2025-11-24
39
Participants Needed
2
Research Sites
52 weeks
Total Duration
On this page
Sponsors
I
Institute of Cancer Research, United Kingdom
Lead Sponsor
P
Prostate Cancer Foundation
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, tolerability, and anti-tumor effects of a combination of oral antibiotics with enzalutamide in patients who have metastatic castration-resistant prostate cancer (mCRPC) that has progressed after prior treatments including taxane chemotherapy and novel androgen axis therapies. This Phase I/II trial aims to explore whether adding antibiotics to enzalutamide can be safely administered and show signs of anti-cancer activity in this patient group. The study involves two phases. Phase I assesses the safety and tolerability of two sequential antibiotic combinations—amoxicillin plus metronidazole for 2 weeks followed by ciprofloxacin plus vancomycin for 2 weeks—given in 4-week cycles alongside daily enzalutamide (160 mg). Enzalutamide treatment continues beyond antibiotic cycles until disease progression or intolerance. Phase II uses a two-stage design to evaluate anti-tumor activity of the safe dose and schedule identified in Phase I, enrolling up to 33 patients who have progressed after prior therapies. Participants will undergo regular monitoring including tumor assessments using RECIST and PCWG3 criteria, biochemical tests, and safety evaluations throughout the 28-day dose-limiting toxicity period and beyond. Study visits include blood tests, imaging, biopsies when feasible, and collection of biological samples for biomarker analysis. Researchers will measure safety, tolerability, response rates, progression-free survival, and other markers related to prostate cancer progression over the course of treatment and follow-up, with recruitment expected to complete within 24 months.
CONDITIONS
Brief Title
Combination Study of Antibiotics With Enzalutamide (PROMIZE)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed metastatic castration-resistant prostate cancer or adenocarcinoma refractory to conventional treatment, or no conventional therapy exists or is declined
- Documented prostate cancer progression by RECIST v1.1 or PCWG3 criteria including soft tissue, bone, PSA progression, or clinical worsening
- Progressed after at least 12 weeks of treatment with a novel androgen axis therapy within 6 months prior to trial entry
- Previously progressed on at least one line of taxane chemotherapy or not fit/willing to receive taxane
- Ongoing androgen deprivation therapy maintaining serum testosterone below 50 ng/dL (less than 2.0 nM)
- Life expectancy of at least 12 weeks
- Able to swallow tablets
- Archival tumor tissue available for analyses
- Willing to have pre- and post-treatment biopsies if feasible
- WHO performance status 0-2
- Hematological and biochemical measures within specified ranges
- Age 18 years or older
- Signed informed consent and able to comply with study requirements including blood, biopsy, urine, rectal swab, and stool sample collection
You will not qualify if you...
- Anti-cancer therapy (surgery, radiotherapy, chemotherapy) within 4 weeks prior to trial entry (6 weeks for bicalutamide)
- Ongoing toxic effects from previous treatments, except certain mild toxicities
- Systemic antibiotic treatment within 12 weeks prior to study entry
- Known allergy or intolerance to penicillin, amoxicillin, metronidazole, vancomycin, ciprofloxacin, or enzalutamide
- History of tendon disorders related to quinolones
- Use of prohibited medications including CYP450 inducers/inhibitors or grapefruit products within 4 weeks prior
- Concurrent treatment with medications causing ototoxicity, neurotoxicity, or nephrotoxicity
- Known or suspected leptomeningeal or untreated brain metastases
- History of stroke, epilepsy, excessive alcohol intake, or significant hearing loss
- Patients with partners of child-bearing potential not agreeing to effective contraception
- Conditions affecting drug absorption or significant gastrointestinal disorders
- High medical risk due to uncontrolled infection or systemic disease
- Significant liver disease or cirrhosis
- Positive for hepatitis B, hepatitis C, or HIV
- Certain cardiac conditions including rhythm abnormalities or QT prolongation
- Prior bone marrow transplant or extensive radiotherapy to marrow within 8 weeks
- Active autoimmune disease requiring immunosuppression
- Current participation in another interventional clinical trial
- Other conditions judged unsuitable by the investigator
- Recent malignancy other than prostate cancer within 3 years (with exceptions)
- Symptoms or current infection with COVID-19
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 8 weeks for antibiotic cycles; enzalutamide continues until disease progression or withdrawal
Participants receive a combination of antibiotics and enzalutamide. Phase I evaluates safety and tolerability of amoxicillin plus metronidazole for 2 weeks followed by ciprofloxacin plus vancomycin for 2 weeks, repeated in 2 cycles (8 weeks total). Enzalutamide is taken daily and continues beyond antibiotic treatment until disease progression, intolerance, or withdrawal.
Visits during treatment cycles with safety monitoring; exact visit frequency varies
Duration - Up to 12 months
Participants are monitored for ongoing safety, tolerability, and anti-tumour activity after antibiotic treatment while continuing enzalutamide. This includes assessments of progression-free survival and response evaluation.
Regular visits for safety and efficacy assessments during follow-up
Trial Site Locations
Total: 2 locations
1
Oncolgy Institute of Southern Switzerland (IOSI)
Bellinzona, Switzerland
Actively Recruiting
2
The Royal Marsden NHS Foundation Trust
Sutton, United Kingdom, SM2 5PT
Actively Recruiting
Research Team
P
PROMIZE Team
B
Bindu Rao Baikady, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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