Table 4 Eligibility criteria for the SPIRE trial

Inclusion criteria

All patients

1. Eastern Cooperative Oncology Group 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-51 EDTA or Tc-99m DTPA clearance

3. Adequate haematological parameters:

 • Haemoglobin ≥ 90 g/L

 • Neutrophil count ≥ 1.5 × 10⁹/L

 • Platelets ≥ 100 × 10⁹/L

4. Adequate biochemical parameters:

 • Bilirubin ≤ 1.5 × upper limit of normal (ULN)

 • ALT and ALP ≤ 2.5 × ULN (ALP ≤ 5 × ULN if caused by liver or bone metastases)

5. Aged 16 years or over

6. Life expectancy > 3 months

7. Provision of written informed consent

Patients in the dose escalation phase:

8. 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:

9. Bladder cancer with a pure or predominant component of transitional cell carcinoma

10. Clinical stage T2-4a N0 M0

11. Planned to commence GC for 3 or 4 cycles with neoadjuvant (i.e. curative) intent prior to a planned radical cystectomy

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 of registration/randomisation

4. Any investigational medicinal product within 30 days registration/randomisation

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 ≥ class II) 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 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:

12. 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