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The University of Southampton
Southampton Clinical Trials Unit

SPIRE TRIAL

Title

A phase Ib/randomised IIa open label clinical trial combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer. 

Description

SGI-110 is a DNA methyltransferase inhibitor developed for optimised delivery of the active metabolite decitabine.

Pre-clinical data support that cisplatin resistance in bladder and other cancers is derived, at least in part, through promotor methylation of silenced genes relevant to a cisplatin resistance phenotype. Experimentally this is reversible through co-administration of DNA hypomethylating agents.

The central hypothesis to be tested in this clinical trial is that SGI-110 can be safely combined with GC in bladder cancer at doses able to induce demethylation of genes associated with cisplatin resistance.

Objectives

PrimaryObjective:

  • To establish a safe and biologically effective dose and schedule for SGI-110 in combination with GC chemotherapy for future phase II/III investigation as a neoadjuvant therapy in bladder cancer.

Secondary Objectives:

  • To evaluate the safety and toxicity profile of SGI-110 when combined with GC.
  • To provide evidence of the pharmacodynamic effect of SGI-110 in combination with GC in blood and bladder cancer tissue.
  • To provide pharmacokinetic data for SGI-110 exposure.
  • To evaluate the safety and deliverability of SGI-110 when combined with GC as a neoadjuvant treatment for muscle invasive bladder cancer prior to radical local therapy.

Trial Design

SPIRE is for a phase Ib/IIa clinical trial to develop a combination of SGI-110 with GC. It incorporates an initial Dose Escalation Phase in advanced solid tumours (including advanced/metastatic bladder cancer). This will be followed by a randomised Dose Expansion Phase in bladder cancer patients receiving neoadjuvant chemotherapy. 

Trial Status

Phase II open to recruitment.

Population

Patients with Bladder cancer with a pure or a predominant component of transitional cell carcinoma, planned to commence Gemcitabine/Cisplatin for 3 or 4 cycles with neoadjuvant (i.e. curative) intent prior to a planned radical cystectomy. 

Trial Team:

Senior Trial Manager:

Ellice Marwood (023 8120 5608)

Trial Manager:

Nicky Downs (023 8120 5302)

Clinical Data Coordinator:

Stephanie Harding (023 8120 5675)

Contact information

Email: spire@soton.ac.uk

Fax: 0844 7740 621

SAE Reporting: ctu@soton.ac.uk or 0844 7740 621

Essential Trial Documents

SPIRE - Protocol v5 07-Feb-2019

SPIRE - Site Visit Log v1 08-Mar-2016

SPIRE - Site Delegation Log v1 20-Jan-2016

SPIRE - Master Patient List - v1 20-Jan-2016

SPIRE - Labels for patient records- Phase II - v1 20-Jan-2016

SPIRE - File Note - Blank

SPIRE - Patient Screening Log v2 31-May-2018

Patient Documents

SPIRE - Patient Information Sheet Phase II - v5 07-Feb-2019

SPIRE - GP Letter Phase II - v2 07-Feb-2019

SPIRE - Informed Consent Form Phase II - v5 07-Feb-2019

SPIRE - Phase II Patient Cards v1 20-Nov-2015

Patient Registration

SPIRE - Phase II Trial Randomisation Form v1 31-May-2018

SPIRE - TENALEA User Manual v1 04-JUN-2018

PD & Translational Sample Documents

SPIRE - Phase II Lab Manual - Main Study and Translational Samples v1 16-Jan-2018

SPIRE - Phase II PD Translational Blood Sample Log v1 31-May-2018

SPIRE - Phase II PD Translational Tumour Sample Log v1 31-May-2018

Pharmacy Documents

SPIRE - SGI-110 Receipt-Destruction Log v1.0 01-Apr-2016

SPIRE - Phase II Drug Dispensing Log - SGI-110 - v2 dated 31-May-2018

SPIRE - Diluent Receipt - Destruction Log v1 01-Apr-2016

SPIRE - Drug Dispensing Log - Cisplatin v1 01-Apr-2016

SPIRE - Drug Dispensing Log - Gemcitabine v1 01-Apr-2016

SPIRE - SGI-110 IST Pharmacy Manual EP10 SPIRE v5 Sep-2018

SPIRE - Phase II Patient Specific Drug Dispensing Log v2 dated 31-May-2018

IMP Shipment Requests

SPIRE - IMP Shipment Request Form - Charring Cross

SPIRE - IMP Shipment Request Form - Guy's and St Thomas

SPIRE - IMP Shipment Request Form - Preston

SPIRE - IMP Shipment Request Form - Royal Marsden Hospital

SPIRE - IMP Shipment Request Form - Southampton

SPIRE - IMP Shipment Request Form - The Christie

SPIRE - IMP Shipment Request Form - Weston Park Hospital

SAE Documents

SPIRE - SAE/SUSAR Report Form v2 31-May-2018

SPIRE - Instructions for Adverse and Serious Adverse Event Reporting v2 31-May-2018

SPIRE - IB SGI-110 v8.1

eCRF

SPIRE - Phase II eCRF Completion Guidelines v2 

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