Health TrialsbyHealthPanel

Combination Study of Antibiotics With Enzalutamide (PROMIZE)

ConditionMetastatic Castration-Resistant Prostate Cancer (mCRPC)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorInstitute of Cancer Research, United Kingdom

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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

Disqualifiers

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).

Trial design

Design model

Single group

Treatments tested in this trial

  • Enzalutamide 40mg

    Drug

    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)

  • Amoxicillin 500mg

    Drug

    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

  • Metronidazole 400mg

    Drug

    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

  • Vancomycin 125mg

    Drug

    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

  • Ciprofloxacin 500g

    Drug

    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

Treatment groups

39 Participants
are divided into 1 treatment group
Group A: mCRPC patients dose with a combination of enzalutamide and antibioticsExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
28 days
2

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.

Time frame
28 days
3

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.

Time frame
28 days

Secondary outcomes

1

To document possible anti-tumour activity in patients in Phase I.

Antitumour activity will be defined by response rate on the same basis as that used for the primary objective of the Phase II component.

Time frame
28 days
2

To evaluate progression-free survival (PFS) in mCRPC patients receiving the antibiotic combinations in Phase I.

PFS will be measured from the date of antibiotic commencement to the date of progression as determined by radiological criteria (RECIST v 1.1, PCWG3 bone scan criteria) or unequivocal clinical progression necessitating drug discontinuation (e.g. worsening pain, spinal cord compression, need for other anticancer therapy).

Time frame
12 months
3

To evaluate PFS in mCRPC patients receiving the antibiotic combinations along with enzalutamide in Phase II.

PFS will be measured from the date of antibiotic commencement to: * The date of progression as determined by radiological criteria (RECIST v1.1, PCWG3 bone scan criteria) and/or * Unequivocal clinical progression necessitating drug discontinuation (e.g. worsening pain, spinal cord compression, need for other anticancer therapy).

Time frame
12 months
4

To determine the time to PSA progression from the date of antibiotic commencement

This is 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.

Time frame
28 days

Other outcomes

1

To report the effect of the antibiotic combinations on the circulating immune cell repertoire.

Serial peripheral white blood cell immunophenotyping.

Time frame
28 days
2

To report the effect of the antibiotic combinations on the tumour.

Tumour cytokine analyses

Time frame
28 days
3

To report the effect of the antibiotic combinations on the circulating chemokine and cytokine expression.

Whole blood cytokine analyses by ELISA.

Time frame
28 days
4

To evaluate the impact of the antibiotic combinations on whole blood transcriptomes.

Serial whole blood transcriptome analyses.

Time frame
28 days

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institute of Cancer Research, United Kingdom

Lead sponsor

Prostate Cancer Foundation

Collaborator

Source ClinicalTrials.gov
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