Combination Study of Antibiotics With Enzalutamide (PROMIZE)
PROMIZE: A Phase I/II Trial to Assess the Safety, Tolerability and Preliminary Anti-tumour Activity of Oral Combination Antibiotic Therapy to Modulate the Microbiome in Combination With Enzalutamide With Metastatic Castration Resistant Prostate Cancer (mCRPC).
1 other identifier
interventional
39
2 countries
2
Brief Summary
PROMIZE is an open-label, multi-centre, single-arm, Phase I/II clinical trial, evaluating the safety, tolerability and anti-tumuor efficacy of an antibiotic combination and enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Nov 2023
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 25, 2023
CompletedStudy Start
First participant enrolled
November 2, 2023
CompletedFirst Posted
Study publicly available on registry
November 13, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
November 24, 2025
November 1, 2025
2.7 years
October 25, 2023
November 19, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Confirm the safety and tolerability of the combination of amoxicillin plus metronidazole (2 weeks) followed by ciprofloxacin plus vancomycin (2 weeks) along with enzalutamide in Phase I in mCRPC patients.
Determine a dose at which no more than one patient out of up to 6 patients experiences a highly probable or probably drug-related DLT, during the 28-day DLT period.
28 days
Describe the safety profile of the antibiotic combinations along with enzalutamide in Phase I.
Causality and grading severity of each adverse event related to the investigational agents according to the NCI CTCAE v5.0.
28 days
Determine the response rate of the antibiotic combinations in patients with mCRPC in Phase II.
Anti-tumour activity will be defined by response rate on the basis of the following outcomes. If any of the following occur, patients will be considered to have responded: * PSA decline ≥ 50% criteria confirmed 4 weeks or later, and/or * Confirmed soft tissue objective response by RECIST (v1.1) in patients with measurable disease.
28 days
Secondary Outcomes (12)
To document possible anti-tumour activity in patients in Phase I.
28 days
To evaluate progression-free survival (PFS) in mCRPC patients receiving the antibiotic combinations in Phase I.
12 months
To evaluate PFS in mCRPC patients receiving the antibiotic combinations along with enzalutamide in Phase II.
12 months
To determine the time to PSA progression from the date of antibiotic commencement
28 days
To determine the duration of PSA decline as an estimate of the biochemical anti-tumour activity of the combination of amoxicillin plus metronidazole (2-weeks) followed by ciprofloxacin plus vancomycin (2-weeks) along with enzalutamide.
28 days
- +7 more secondary outcomes
Other Outcomes (5)
To report the effect of the antibiotic combinations on the circulating immune cell repertoire.
28 days
To report the effect of the antibiotic combinations on the tumour.
28 days
To report the effect of the antibiotic combinations on the circulating chemokine and cytokine expression.
28 days
- +2 more other outcomes
Study Arms (1)
mCRPC patients dose with a combination of enzalutamide and antibiotics
EXPERIMENTALPhase I: The evaluation of the safety and tolerability of the combinations of amoxicillin plus metronidazole, and ciprofloxacin plus vancomycin with enzalutamide. Phase II: Determination of the anti-tumour activity of the combinations of amoxicillin plus metronidazole, and ciprofloxacin plus vancomycin with enzalutamide.
Interventions
Enzalutamide is presented in 40mg yellow film-coated tablets. They are supplied in a cardboard wallet incorporated a PVC/PCTFE/aluminium blister pack which holds 28 tablets. Each carton contains 4 wallets (112 tablets in total)
Red / Buff coloured size '0' capsules containing white to off white powder printed with 'AMOXY 500 ' in black ink OR White to off-white granular powder filled in hard gelatine capsule shells size '0'. Scarlet colour cap, buff colour body printed with 'AMOXY' on cap and '500' on body OR White/Maroon size '0' capsules containing white to yellowish granular powder
Yellow, circular (11mm), biconvex, film-coated tablets with '400' debossed on one side and plain on other side OR White to off white coloured, caplet shaped (17.00 x 6.00 mm) film-coated tablets, debossed "400" on one side and plain on other side OR Off-white coloured, round, biconvex uncoated tablets engraved "MZ 400" \& break line on one side and plain on other
Grey/pink 17.8 ± 0.40 mm hard capsules each containing 125mg, containing white to off white congealed liquid mixture as solid mass OR Dark blue and brown hard capsules, imprinted with 3125 in red ink OR Brown 21.4 ± 0.40 mm hard capsule, containing white to off white congealed liquid mixture as solid mass
White to off white, capsule shaped, film coated tablets, with a score line on one side and debossed with 'F22' on the other side. The tablet can be divided into equal doses. The size is 18.2 mm x 8.1 mm OR White, caplet shaped film-coated tablets debossed with '500' on one side and plain on the other side OR White to off-white, capsule shape, biconvex with bevelled edge, film coated tablet with inscription 'CI' on one side and plain on the other side OR White, oval shaped film-coated tablets debossed 'C500' on one side and breakline on other side
Eligibility Criteria
You may qualify if:
- Histologically or cytologically proven metastatic castration-resistant prostate cancer or adenocarcinoma refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient.
- Documented prostate cancer progression as assessed by the investigator with RECIST (v1.1) and PCWG3 criteria with at least one of the following criteria:
- Progression of soft tissue/visceral disease by RECIST (v1.1) and/or,
- Progression of bone disease by PCWG3 bone scan criteria and/or,
- Progression of PSA by PCWG3 PSA criteria and/or
- Clinical progression with worsening pain and need for palliative radiotherapy for bone metastases.
- Phase I: Patients that have progressed after at least 12 weeks of treatment with a NAAT within the previous 6 months Phase II: Patients that have progressed after at least 12 weeks of treatment with a NAAT within the previous 6 months (for combination treatment) or more than 6 months prior to trial entry (for enzalutamide alone resistance run-in).
- Previously progressed on at least one line of taxane chemotherapy (or not fit or not willing to receive a taxane).
- Ongoing androgen deprivation maintaining serum testosterone of less than 50 ng/dL (less than 2.0 nM) is mandatory.
- Life expectancy of at least 12-weeks.
- Able to swallow tablets.
- Archival tumour tissue must be available for analyses.
- Willing to have pre- and post-treatment biopsies if biopsy is feasible.
- World Health Organisation (WHO) performance status of 0-2 (Appendix 1).
- Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) prior to the patient's first dose of IMP.
- +11 more criteria
You may not qualify if:
- Patients receiving enzalutamide immediately preceding the trial will be able to continue on enzalutamide without washout.
- Prior flutamide treatment during previous 4-weeks. N.B. Patients whose PSA did not decline in response to antiandrogens given as a second line or later intervention will only require a 14-day washout;
- Prior bicalutamide (Casodex) and nilutimide (Nilandron) treatment during previous 6-weeks;
- Prior progesterone, medroxyprogesterone, progestins, cyproterone acetate, tamoxifen, and 5-alpha reductase inhibitors during previous 2-weeks (14-days).
- Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the DDU should not exclude the patient.
- Previous treatment with any systemic antibiotic within 12 weeks of study entry.
- Known hypersensitivity reaction or intolerance to any penicillin, amoxicillin, metronidazole, vancomycin, ciprofloxacin or enzalutamide.
- History of tendon disorder secondary to quinolones
- Use of drugs that are listed in the prohibited concomitant medications section including strong inducers and inhibitors of CYP450 (please refer to http://medicine.iupui.edu/clinpharm/ddis/table.aspx). Seville orange or grapefruit products and any herbal medications should be avoided for 4 weeks prior to starting trial treatment.
- Concurrent treatment with prohibited medications which include medications that causes ototoxicity, neurotoxicity, and nephrotoxicity.
- Known or suspected leptomeningeal metastases or untreated brain metastasis. Patients with brain metastases that have been treated and have been shown to be radiologically stable for more than 6 months may be considered for the trial.
- History of stroke, epilepsy or current excessive alcohol intake. History of clinically significant hearing loss including but not limited to congenital hearing loss, need for hearing aids, ongoing acute or chronic ear infection, history of tympanic membrane perforation, tinnitus, vertigo, Meniere disease, cerebrovascular ischemia.
- History of clinically significant hearing loss including but not limited to congenital hearing loss, need for hearing aids, ongoing acute or chronic ear infection, history of tympanic membrane perforation, tinnitus, vertigo, Meniere disease, cerebrovascular ischemia.
- Patients with partners of child-bearing potential (unless they agree to use a barrier method of contraception \[condom plus spermicide\] or to sexual abstinence effective from the first administration of any of the investigational agents, throughout the trial and for 6 months afterwards. Patients with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence). Patients with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate.
- NB. Abstinence is only considered to be an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Oncolgy Institute of Southern Switzerland (IOSI)
Bellinzona, Switzerland
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT, United Kingdom
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Johann De Bono, MD
National Health Service, United Kingdom
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 25, 2023
First Posted
November 13, 2023
Study Start
November 2, 2023
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2027
Last Updated
November 24, 2025
Record last verified: 2025-11