Urothelial cancer Cancer Malignant neoplasms of urinary tract
Conditions
Interventions
Current interventions as of 31/07/2023:
DESIGN
RE-ARM is a phase II trial that will take place at several NHS hospitals around the country. It will recruit 102 participants from approximately 20 parti
Sponsors
Institute of Cancer Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 31/07/2023: 1. Histologically confirmed metastatic urothelial carcinoma not amenable to curative treatment with surgery or radiotherapy. Mixed histology is permitted if predominantly TCC 2. Patients experiencing progressive disease (according to local investigator assessment) during up to six months of treatment with either open-label atezolizumab* (first, second or third line¥) or maintenance avelumab (following platinum-based chemotherapy); or patients with an overall best response of stable disease after a minimum of 3 cycles and a maximum of six months of open label atezolizumab 3. At least one extra-cranial metastatic site suitable for radiotherapy (see section 9.1) 4. At least one RECIST v1.1 measurable lesion distant to the planned site of radiotherapy 5. No radiotherapy within four weeks prior to starting pre-study atezolizumab/avelumab or during atezolizumab or avelumab treatment 6. Satisfactory haematological and biochemical profile (Hb >90 g/L, Plt>100 x 109/L, WBC > 3.0 x 109/L, creatinine 90 g/L, Plt>100 x 10^9/L, WBC >3.0 x 10^9/L, creatinine =18 years 9. Written informed consent * In accordance with therapeutic indications as stated in the current summary of product characteristics ¥ Neoadjuvant treatment received more than a year prior to trial entry will not be considered a line of treatment
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 31/07/2023: 1. Any contraindication to atezolizumab treatment in the local investigator’s opinion (e.g. toxicity [see Section 9.2.8], rapidly progressive disease requiring alternative treatment such as chemotherapy) 2. Greater than 8 weeks since the last dose of atezolizumab or maintenance avelumab 3. Over 6 months’ treatment with atezolizumab or maintenance avelumab prior to randomisation 4. Planned or anticipated clinical need for palliative radiotherapy within 9 weeks following trial entry 5. Received any anti-PD1/PD-L1 or anti-CTLA-4 therapy prior to commencement of atezolizumab or maintenance avelumab 6. Received atezolizumab in combination with chemotherapy 7. Immunosuppressive treatment (apart from corticosteroids at a dose equivalent of prednisolone =10 mg daily) within 2 weeks prior to randomisation. 8. Contraindication to radiotherapy (e.g. radiation sensitivity syndrome) 9. Autoimmune disease requiring active immunotherapy treatment or with life-threatening complications. Patients with vitiligo, controlled psoriasis, autoimmune thyroid disease, type 1 diabetes will be eligible 10. History of pneumonitis 11. Presence of known active brain metastases (brain metastases which have received treatment and are controlled do not preclude randomisation) 12. Active HIV, hepatitis B or hepatitis C infection – patients with asymptomatic or controlled disease may join the trial following review and approval by the Chief Investigator. Participants with these conditions, either active or previous, are not eligible to provide samples for the translational substudy 13. Pregnant or lactating women 14. Administration of a live, attenuated vaccine within 28 days prior to study entry 15. Anticipated life expectancy <10 weeks Previous exclusion criteria: 1. Any contraindication to continued atezolizumab treatment in the local investigator’s opinion (e.g. toxicity, rapidly progressive disease requiring alternative treatment such as chemotherapy) 2. Received anti-PD1/PD-L1, anti-CTLA-4 therapy prior to commencement of atezolizumab 3. Received atezolizumab in combination with chemotherapy 4. Immunosuppressive treatment (apart from corticosteroids at a dose equivalent of prednisolone <=10mg daily) within 2 weeks prior to study entry 5. Contraindication to radiotherapy (e.g. radiation sensitivity syndrome) 6. Autoimmune disease requiring active immunotherapy treatment or with life-threatening complications. Patients with vitiligo, controlled psoriasis, autoimmune thyroid disease, and type 1 diabetes will be eligible. 7. History of pneumonitis 8. Presence of known active brain metastases (brain metastases which have received treatment and are controlled do not preclude trial entry) 9. Active HIV, hepatitis B or hepatitis C infection – patients with asymptomatic or controlled disease may join the trial following review and approval by the Chief Investigator 10. Pregnant or lactating women 11. Administration of a live, attenuated vaccine within 28 days prior to study entry 12. Anticipated life expectancy <10 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate according to RECIST v1.1 at 9 weeks after the start of study | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective response rate according to iRECIST at nine weeks after the start of study 2. Clinical benefit according to RECIST v1.1 at nine weeks after the start of study 3. Best response according to RECIST v1.1 at six months after the start of study 4. Duration of response measured using patient records at the end of the study 5. Time to progression measured using patient records at the end of the study 6. Progression free survival measured using patient records at the end of the study 7. Overall survival measured using patient records at the end of the study 8. Treatment related toxicity (CTCAE v5) at the end of the study 9. Patient reported quality of life (EORTC QLQ-C30 & EQ-5D-5L) up to 12 months | — |
Countries
England, United Kingdom
Outcome results
None listed