Comparing 3 vs 6 Cycles of Platinum-based Chemotherapy Prior to Maintenance Avelumab in Advanced Urothelial Cancer

ConditionUrinary Bladder Neoplasms

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorQueen Mary University of London

About this trial

This is an adaptive, open-label, randomised phase II trial that aims to evaluate the impact of 3 vs 6 cycles of first-line platinum-based chemotherapy followed by maintenance avelumab in the quality of life of patients with locally advanced or metastatic urothelial cancer. Initially, 224 eligible and evaluable patients (112 in each arm) will receive 3 cycles vs 6 cycles of 3-weekly gemcitabine plus cisplatin/carboplatin, followed by 2-weekly maintenance avelumab until disease progression or intolerable toxicities. Avelumab treatment will be given up to a maximum of 2 years from the end of chemotherapy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Willing and able to provide written informed consent.

Ability to comply with the protocol, including but not limited to, the repeated completion of the EORTC QLQ-C30 questionnaires.

Age ≥ 18 years.

Histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Patients with squamous or sarcomatoid differentiation or mixed cell types are eligible but a component of urothelial cancer is required.

Disqualifiers

1. Prior treatment with a PD-(L)-1 inhibitor for any advanced malignancy. Treatment with PD-(L)-1 inhibitors in the neoadjuvant or adjuvant setting for UC are permitted.

Trial design

Design model

Parallel

Treatments tested in this trial

Avelumab
Drug
Avelumab treatment will be given up to a maximum of 2 years from the end of chemotherapy

Treatment groups

320 Participants

are divided into 2 treatment groups

Group A: 3 cycles of gemcitabine + cisplatin/carboplatin followed by avelumabExperimental treatment 1 intervention

Group B: 6 cycles of gemcitabine + cisplatin/carboplatin followed by avelumabActive comparator 1 intervention

Trial outcomes

Primary outcomes

To evaluate the effect of 3 vs 6 cycles platinum-based, front-line chemotherapy followed by maintenance avelumab based on patient-reported outcomes (PROs) in the study population.

Change in GHS/QoL scale scores from baseline to completion of 6 cycles of treatment. Patients who withdraw from treatment between Cycles 4 and 6 will be included, provided an EORTC QLQ-C30 questionnaire is completed within 14 days from the date of withdrawal.

Time frame

Cycle 6 (Arm A: 3x cycles of chemotherapy (21 days per cycle) plus 3x cycles of Avelumab (28 days per cycle), Arm B: 6 cycles of chemotherapy only (21 days per cycle)

Secondary outcomes

To evaluate the effect of 3 vs 6 cycles platinum-based, front-line chemotherapy followed by maintenance avelumab based on additional patient-reported outcomes (PROs) in the study population.

Quality of Life Assessment using the GHS/QOL scale score

Time frame

10 cycles of treatment (Arm A: 3x cycles of chemotherapy (21 days per cycle) plus 7x cycles of Avelumab (28 days per cycle), Arm B: 6 cycles of chemotherapy (21 days per cycle) followed by 4x cycles of avelumab (28 days per cycle))

To evaluate the effect of 3 vs 6 cycles platinum-based, front-line chemotherapy followed by maintenance avelumab based on clinician reported outcomes.

Performance Status as measured by the Karnofsky Scale on completion of 6 cycles of treatment.

Time frame

On completion of 6 cycles of treatment (From baseline to completion of cycle 6 (Arm A: 3x cycles of chemotherapy (21 days per cycle) plus 3x cycles of Avelumab (28 days per cycle), Arm B: 6 cycles of chemotherapy only (21 days per cycle)))

To evaluate the safety and tolerability of 3 vs 6 cycles of platinum-based, front-line chemotherapy followed by maintenance avelumab therapy.

Adverse events graded according to NCI-CTCAE v5.0

Time frame

From baseline throughout treatment (From baseline to completion of cycle 6 (Arm A: 3x cycles of chemotherapy followed by Avelumab, Arm B: 6 cycles of chemotherapy followed by Avelumab) for a maximum of 2 years on avelumab.

To assess the efficacy of 3 vs 6 cycles platinum based, front-line chemotherapy followed by maintenance avelumab in patients with advanced UC.

Efficacy endpoints

Time frame

Baseline until end of trial participation (maximum of 2 years on avelumab)