Informazioni generali
  • Categoria della malattia Cancro della prostata (BASEC)
  • Fase dello studio Phase 1/Phase 2 (ICTRP)
  • Stato di reclutamento reclutamento in corso (BASEC/ICTRP)
  • Luogo dello studio
    Bellinzona
    (BASEC)
  • Responsabile dello studio Professor Andrea Alimonti andrea.alimonti@ior.iosi.ch (BASEC)
  • Fonte dati BASEC: Importato da 29.04.2025 ICTRP: Importato da 06.06.2025
  • Ultimo aggiornamento 06.06.2025 02:00
HumRes66033 | SNCTP000006175 | BASEC2024-01366 | NCT06126731

Clinical study to evaluate the safety and efficacy of an antibiotic therapy in combination with enzalutamide in metastatic hormone-resistant prostate cancer

  • Categoria della malattia Cancro della prostata (BASEC)
  • Fase dello studio Phase 1/Phase 2 (ICTRP)
  • Stato di reclutamento reclutamento in corso (BASEC/ICTRP)
  • Luogo dello studio
    Bellinzona
    (BASEC)
  • Responsabile dello studio Professor Andrea Alimonti andrea.alimonti@ior.iosi.ch (BASEC)
  • Fonte dati BASEC: Importato da 29.04.2025 ICTRP: Importato da 06.06.2025
  • Ultimo aggiornamento 06.06.2025 02:00

Descrizione riassuntiva dello studio

Patients with progression on enzalutamide or another NAAT within 6 months of study entry will start taking the combination of antibiotics and enzalutamide simultaneously. Patients with progression on enzalutamide or another NAAT more than 6 months prior to study entry will start taking only enzalutamide (run-in for enzalutamide resistance) to confirm resistance to enzalutamide. Once disease progression is confirmed, the patient will start the combination of antibiotics and enzalutamide.

(BASEC)

Intervento studiato

Combination of antibiotics and enzalutamide

(BASEC)

Malattie studiate

metastatic hormone-resistant prostate carcinoma

(BASEC)

Criteri di partecipazione
- Metastatic hormone-resistant prostate carcinoma, histologically or cytologically confirmed - Progression of prostate cancer - Progression after at least one line of chemotherapy with taxanes - Ongoing androgen deprivation maintaining serum testosterone below 50 ng/dL - Willingness to undergo pre- and post-treatment biopsies if biopsy is feasible - 18 years or older (BASEC)

Criteri di esclusione
- Surgical intervention, radiotherapy, chemotherapy, or other antitumor therapy within 4 weeks prior to study entry - Previous treatment with any systemic antibiotic within 12 weeks prior to study entry - Known hypersensitivity or intolerance to penicillin, amoxicillin, metronidazole, vancomycin, ciprofloxacin, or enzalutamide - History of tendon disorders secondary to fluoroquinolones - Use of medications listed in the "Prohibited Concomitant Medications" section of the protocol, including strong inducers and inhibitors of CYP450. - Any medical condition described in the protocol (BASEC)

Luogo dello studio

Bellinzona

(BASEC)

Switzerland, United Kingdom (ICTRP)

Sponsor

Institute of Cancer Research, Sutton, UK CTU-EOC Clinical Trial Unit Ente Ospedaliero Cantonale

(BASEC)

Contatto per ulteriori informazioni sullo studio

Persona di contatto in Svizzera

Professor Andrea Alimonti

+41 91 821 0071

andrea.alimonti@ior.iosi.ch

Istituto oncologico di ricerca (IOR)

(BASEC)

Informazioni generali

National Health Service, United Kingdom

02087224497

andrea.alimonti@ior.iosi.ch

(ICTRP)

Informazioni generali

National Health Service, United Kingdom

02087224497

andrea.alimonti@ior.iosi.ch

(ICTRP)

Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)

Commissione d'etica Ticino

(BASEC)

Data di approvazione del comitato etico

11.11.2024

(BASEC)


ID di studio ICTRP
NCT06126731 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
Studio di fase I/II per valutare la sicurezza, la tollerabilità e l'attività antitumorale preliminare di una terapia antibiotica combinata orale per modulare il microbioma in combinazione con enzalutamide nel carcinoma prostatico metastatico resistente alla castrazione (mCRPC) (BASEC)

Titolo accademico
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). (ICTRP)

Titolo pubblico
Combination Study of Antibiotics With Enzalutamide (PROMIZE) (ICTRP)

Malattie studiate
Metastatic Castration-Resistant Prostate Cancer (mCRPC) (ICTRP)

Intervento studiato
Drug: Vancomycin 125mgDrug: Enzalutamide 40mgDrug: Amoxicillin 500mgDrug: Metronidazole 400mgDrug: Ciprofloxacin 500g (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Inclusion Criteria:

1. 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.

2. Documented prostate cancer progression as assessed by the investigator with RECIST
(v1.1) and PCWG3 criteria with at least one of the following criteria:

1. Progression of soft tissue/visceral disease by RECIST (v1.1) and/or,

2. Progression of bone disease by PCWG3 bone scan criteria and/or,

3. Progression of PSA by PCWG3 PSA criteria and/or

4. Clinical progression with worsening pain and need for palliative radiotherapy
for bone metastases.

3. 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).

4. Previously progressed on at least one line of taxane chemotherapy (or not fit or not
willing to receive a taxane).

5. Ongoing androgen deprivation maintaining serum testosterone of less than 50 ng/dL
(less than 2.0 nM) is mandatory.

6. Life expectancy of at least 12-weeks.

7. Able to swallow tablets.

8. Archival tumour tissue must be available for analyses.

9. Willing to have pre- and post-treatment biopsies if biopsy is feasible.

10. World Health Organisation (WHO) performance status of 0-2 (Appendix 1).

11. 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.

Haemoglobin (Hb): = 9.0 g/dL

Absolute neutrophil count: = 1.5 x 109/L

Platelet count: = 75 x 109/L

Serum bilirubin: = 1.5 x upper limit of normal (ULN)

Alanine aminotransferase (ALT): = 2.5 x (ULN) unless raised due to tumour in which
case up to 5 x ULN is permissible

Aspartate aminotransferase (AST): = 2.5 x (ULN) unless raised due to tumour in which
case up to 5 x ULN is permissible

Serum creatinine / calculated creatinine clearance: = 1.5 x upper limit of normal
(ULN) / GFR = 50 mL/min (uncorrected value)

Serum albumin: >25 g/L

12. 18 years or over

13. Written (signed and dated) informed consent and be capable of co-operating with
treatment and follow-up

14. Willing and able to comply with the study requirement including the collection of
blood, fresh tumour biopsy, urine, rectal swab and stool samples.

Exclusion criteria:

1. Surgery, radiotherapy, chemotherapy, or other anti-cancer therapy within 4-weeks
prior to trial entry into the study (6 weeks for bicalutamide). The use of
bisphosphonates or RANK ligand inhibitors in patients with known osteopenia or
osteoporosis or bone metastases is permitted. Prior antiandrogenic treatment
exclusions as follows:

- 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).

2. 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.

3. Previous treatment with any systemic antibiotic within 12 weeks of study entry.

4. Known hypersensitivity reaction or intolerance to any penicillin, amoxicillin,
metronidazole, vancomycin, ciprofloxacin or enzalutamide.

5. History of tendon disorder secondary to quinolones

6. 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.

7. Concurrent treatment with prohibited medications which include medications that
causes ototoxicity, neurotoxicity, and nephrotoxicity.

8. 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.

9. 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.

10. 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.

11. 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

12. Any condition that would increase enteral absorption in the opinion of the
investigator, including but not limited to malabsorption syndromes, impaired GI
motility, chronic pancreatitis, partial or complete gastric and/or bowel resections,
history of clinically significant gastrointestinal bleeding in the last 6 months,
history of mesenteric ischemia or bowel obstruction, chronic diarrhoea (=Grade 2),
inflammatory bowel disease (Crohn's disease, ulcerative colitis).

13. At high medical risk because of non-malignant syst (ICTRP)

non disponibile

Endpoint primari e secondari
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.;Describe the safety profile of the antibiotic combinations along with enzalutamide in Phase I.;Determine the response rate of the antibiotic combinations in patients with mCRPC in Phase II. (ICTRP)

To document possible anti-tumour activity in patients in Phase I.;To evaluate progression-free survival (PFS) in mCRPC patients receiving the antibiotic combinations in Phase I.;To evaluate PFS in mCRPC patients receiving the antibiotic combinations along with enzalutamide in Phase II.;To determine the time to PSA progression from the date of antibiotic commencement;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.;To determine the maximum percentage and absolute PSA decline from baseline;To determine the radiologic PFS (rPFS) of the combination of antibiotics and enzalutamide in Phase II.;To determine the time to radiologic progression to the combination of antibiotics and enzalutamide in Phase II.;To estimate the OS in mCRPC patients receiving the antibiotic combinations along with enzalutamide in Phase II.;To further characterise the safety and tolerability profile of the antibiotic combinations with enzalutamide in Phase II.;To identify biomarkers of response to the antibiotic combinations and of anti-tumour activity in Phase II.;To evaluate the peripheral circulation neutrophil-to-lymphocyte ratio (NLR) as a determinant of response to to treatment in Phase II. (ICTRP)

Data di registrazione
25.10.2023 (ICTRP)

Inclusione del primo partecipante
non disponibile

Sponsor secondari
Prostate Cancer Foundation (ICTRP)

Contatti aggiuntivi
Johann De Bono, MDHannah Badham, MSc, hannah.badham@icr.ac.uk, 02087224497, National Health Service, United Kingdom (ICTRP)

ID secondari
CCR5461 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT06126731 (ICTRP)

Risultati dello studio

Riepilogo dei risultati

non disponibile

Link ai risultati nel registro primario

non disponibile