SGI-110 with cisplatin and gemcitabine chemotherapy in patients with bladder cancer

ISRCTN	ISRCTN16332228
DOI	https://doi.org/10.1186/ISRCTN16332228
EudraCT/CTIS number	2015-004062-29
Secondary identifying numbers	20447

Submission date: 03/02/2016
Registration date: 03/02/2016
Last edited: 04/06/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-sgi-110-with-cisplatin-and-gemcitabine-for-advanced-solid-tumours-spire

Contact information

Ms Denise Dunkley
Public

University of Southampton
University Road
Southampton
SO17 1BJ
United Kingdom

Phone	+44 (0)23 8120 5328
Email	spire@soton.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
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
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(s)	North West - Haydock Research Ethics Committee, 14/01/2016, ref: 15/NW/0936
Condition	Bladder cancer
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
Pharmaceutical study type(s)
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	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 study start date	01/04/2016
Overall study end date	24/04/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	Planned Sample Size: 56; UK Sample Size: 56
Total final enrolment	39
Participant inclusion criteria	Current participant inclusion criteria as of 26/06/2019: 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 Previous 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 exclusion criteria	Current participant exclusion criteria as of26/06/2019: 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. 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 7. 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) 8. Patients of child-bearing potential who are not using, or who are unwilling to use, a highly effective method of contraception 9. Any patient who, in the judgment of the local investigator, is unlikely to comply with trial procedures, restrictions or requirements 10. Any patient who has received a live vaccine within 4 weeks of initiation of their treatment Patients in the dose expansion phase: Current separate other malignancy. Current non‐melanoma skin cancer, cervical carcinoma in situ or incidental localised prostate cancer is permissible. Other prior malignancy is acceptable if the treatment within the SPIRE trial would be given with curative intent. Previous 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	26/09/2019

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University of Southampton

University Road
Southampton
SO17 1BJ
United Kingdom

Sponsor information

Southampton University Hospitals NHS Trust
Hospital/treatment centre

Tremona Road
Southampton
Hampshire
SO16 6YD
England
United Kingdom

"ROR"	https://ror.org/0485axj58

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	31/12/2020
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
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 plan	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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	03/04/2018		Yes	No
Results article	results	01/04/2021	22/01/2021	Yes	No
Plain English results			07/09/2021	No	Yes

Editorial Notes

04/06/2024: Internal review.
07/09/2021: Cancer Research UK lay results summary link added.
22/01/2021: Publication reference added.
15/10/2020: The intention to publish date was changed from 31/08/2020 to 31/12/2020.
15/07/2020: The intention to publish date was changed from 30/06/2020 to 31/08/2020.
22/04/2020: The overall trial end date was changed from 31/03/2020 to 24/04/2020.
01/11/2019: The total final enrolment was added.
31/10/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/08/2019 to 26/09/2019.
2. The overall end date was changed from 31/01/2020 to 31/03/2020.
3. The intention to publish date was changed from 01/01/2021 to 30/06/2020.
26/06/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/05/2019 to 31/08/2019.
2. The overall end date was changed from 01/08/2019 to 31/01/2020.
3. The intention to publish date was changed from 01/01/2020 to 01/01/2021.
4. The participant inclusion criteria were changed.
5. The participant exclusion criteria were changed.
02/04/2019: The condition has been changed from "Topic: Cancer; Subtopic: Bladder Cancer; Disease: Bladder (advanced), Bladder (superficial)" to "Bladder cancer" following a request from the NIHR.
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.