Condition category
Cancer
Date applied
03/02/2016
Date assigned
03/02/2016
Last edited
12/07/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Ms Denise Dunkley

ORCID ID

Contact details

University of Southampton
University Road
Southampton
SO17 1BJ
United Kingdom
+44 (0)23 8120 5328
spire@soton.ac.uk

Additional identifiers

EudraCT number

2015-004062-29

ClinicalTrials.gov number

Protocol/serial number

20447

Study information

Scientific title

SGI-110 to potentiate platinum response: a phase Ib/randomised IIa open label clinical trial combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer

Acronym

Study hypothesis

Phase I:
The aim of this phase is to find the optimum dose of gemcitabine (GC) for the treatment of bladder cancer to use in the phase II of the study.

Phase II:
The aim of this phase is to investigate the whether treatment with a combination of SGI-110 and GC or GC alone is most effective.

Ethics approval

North West - Haydock Research Ethics Committee, 14/01/2016, ref: 15/NW0936

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: Cancer; Subtopic: Bladder Cancer; Disease: Bladder (advanced), Bladder (superficial)

Intervention

Phase I: Dose-escalation phase
Patients will be entered into sequential dose level cohorts and (at the relevant dose level). Escalating dose level cohorts (4 cohorts are planned) of SGI-110 + standard gemcitabine/cisplatin chemotherapy for up to 6 cycles of 21 days each.

Phase II: Dose expansion phase
Patients will be randomised to one of two groups.

Group 1: Participants receive 3-4 cycles (21 days each) of standard GC chemotherapy + SGI-110 (at the RP2D established in Phase I)

Group 2: Participants receive 3-4 cycles (21 days each) of standard GC chemotherapy only.

Intervention type

Drug

Phase

Phase I/II

Drug names

SGI-110, cisplatin, gemcitabine

Primary outcome measure

To establish the Recommended Phase II Dose (RP2D) for SGI-110 when combined with GC within the first year of the study.

Secondary outcome measures

1. Investigation of other potential pharmacodynamic biomarkers for SGI-110 target is measured at the end of the study
2. Pharmacokinetics of SGI-110 when combined with GC are determined within the first year of the study
3. The pathological complete response rate of bladder cancer patients is measured at the end of the study
4. Toxicity profile of SGI-110 when combined with GC is measured throughout the trial

Overall trial start date

01/04/2016

Overall trial end date

01/08/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

All patients:
1. ECOG performance status of 0 or 1
2. Glomerular filtration rate estimation of = 60 mL/min according to either the Cockcroft and Gault formula or by Cr-51EDTA or Tc-99m DTPA clearance
3. Adequate haematological parameters:
3.1. Haemoglobin = 90 g/dL
3.2. Neutrophil count = 1.5 x109/L
3.3. Platelets = 100 x109/L
4. Adequate biochemical parameters
4.1. Bilirubin = 1.5 x ULN
4.2. ALT and ALP = 2.5 x ULN (ALP = 5 x ULN if caused by liver or bone metastases)
5. Aged 16 years or over
6. Life expectancy greater than 3 months
7. Provision of written informed consent

Patients in the dose escalation phase:
Incurable histologically or cytologically confirmed, locally advanced or metastatic, solid cancer, for which the use of gemcitabine and cisplatin is a clinically appropriate treatment in the view of the local principal investigator. Any number of previous lines of systemic chemotherapy is permitted.

Patients in the dose expansion phase:
1. Bladder cancer with a pure or a predominant component of transitional cell carcinoma
2. Clinical stage T2-4a N0 M0
3. Planned to commence GC for 3 or 4 cycles with neoadjuvant (i.e. curative) intent prior to a planned radical cystectomy

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 56; UK Sample Size: 56

Participant exclusion criteria

All patients:
1. Unresolved toxicities from prior therapy greater than CTCAE v4.03 grade 1 (with the exception of alopecia) at the time of registration
2. Prior radiotherapy to > 30% of bone marrow
3. Major surgery within 30 days
4. Any investigational medicinal product within 30 days
5. Allergy or other known intolerance to any of the proposed study drugs including supportive agents and inclusive of G-CSF and locally utilised anti-emetics
6. Previously-identified central nervous system metastases unless treated and clinically stable and not requiring steroids for at least 4 weeks prior to the start of trial treatment
7. Coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris or congestive cardiac failure (New York Heart Association = grade 2) within the last 6 months
8. Women who are pregnant or breast feeding. (Women of child-bearing potential must have a negative pregnancy test performed within 7 days prior to the start of trial treatment)
9. Patients of child-bearing potential who are not using, or who are unwilling to use, a highly effective method of contraception
10. Any patient who, in the judgment of the local investigator, is unlikely to comply with trial procedures, restrictions or requirements
11. Any patient who has received a live vaccine within 4 weeks of initiation of their treatment

Patients in the dose expansion phase:
Recent or current separate other malignancy. Current non-melanoma skin cancer, cervical carcinoma in situ or incidental localised prostate cancer is permissible. Participants with a history of a separate other malignancy having completed all active treatment 2 or more years previously may be entered.

Recruitment start date

01/04/2016

Recruitment end date

01/05/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Southampton
University Road
Southampton
SO17 1BJ
United Kingdom

Sponsor information

Organisation

Southampton University Hospitals NHS Trust

Sponsor details

Tremona Road
Southampton
Hampshire
SO16 6YD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

A ‘Trials in Progress’ abstract was accepted at ASCO (June 2018) for the phase I part of the trial and an abstract has been submitted to ESMO (Oct 2018).

IPD sharing statement
Data won’t automatically be available upon request but the trialists are happy to consider data sharing approaches (based on consent and contractual obligations) through the Trial Management Group, based on scientific merit.

Intention to publish date

01/01/2020

Participant level data

Other

Basic results (scientific)

Publication list

2018 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/29615077

Publication citations

Additional files

Editorial Notes

12/07/2018: IPD sharing statement added. 10/07/2018: The following changes were made to the trial record: 1. The contact details were updated. 2. The recruitment end date was changed from 01/05/2018 to 01/05/2019. 3. The overall trial end date was changed from 01/05/2018 to 01/08/2019. 4. The intention to publish date was changed from 01/05/2019 to 01/01/2020. 5. Publication and dissemination plan added. 06/04/2018: Publication reference added. 02/08/2016: Cancer Help UK lay summary link added.