Pembrolizumab in Muscle Invasive/Metastatic Bladder Cancer — PLUMMB  

Invasive Bladder Cancer Clinical Trial

Official title: Phase I Study of Hypofractionated Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) in the Treatment of Advanced Bladder Cancer

Status Recruiting

Clinical Trial Summary

PLUMMB is an phase I trial to investigate the safety, tolerability and effectiveness of an immunotherapy drug called Pembrolizumab used in combination with radiotherapy. The study will also investigate two different doses of pembrolizumab, starting at 100mg (through an intravenous drip) and increasing to 200mg for the next cohort of patients, if the first dose is well tolerated. The patients suitable for this study will be: Group A those with locally advanced bladder cancer or Group B patients whose cancer has spread from the bladder (metastatic bladder cancer).

Treatment in the PLUMMB trial will start with a pembrolizumab 2 weeks prior to starting a course of 4 - 6 weeks radiotherapy. Treatment with pembrolizumab will then be given every three weeks. Patients in Group A will then continue to take pembrolizumab for up to a year unless they have disease progression or unacceptable side effects in the meantime. Patients in Group B will continue taking pembrolizumab for as long as needed until they have disease progression or unacceptable side effects.

Patients will be seen every 3 weeks during treatment and every 3-6 months thereafter. CT scans will be done every 3 months during treatment and as per usual care (usually 6 monthly) after the treatment has finished. Patients in Group A will also have a cystoscopy (camera test) to look into the bladder 3 months after they finish radiotherapy. This is standard care and would be the same for patients not on a research study.

Clinical Trial Description

1. Risk and burden for patients

Patients in this study have cancer that often proves hard to control with standard care. The early phase nature of this study means that the intervention may not have any benefit for patients who take part in the study. However, they will still receive the standard treatment of radiotherapy. Throughout the study, any patients who have significant side effects from the trial drug will be withdrawn from the trial and will still be eligible to receive standard care. The study itself carries a number of potential burdens:

• Experimental nature of the study drug. The drug stimulates the immune system to produce more proteins that will attack the tumour cells. It is thought that this will be selective for tumour cells; however it is possible that effects on normal tissues may cause side effects. These risks will be managed as much as possible by regular (3 weekly) clinical assessments as a hospital outpatient, by experienced clinicians while having the study treatment. Comprehensive assessments for safety will be carried out including more intensive monitoring with blood tests.

• Burden of frequent hospital visits and tests. Participants in this study must attend hospital frequently for safety reasons to check for any toxicity of the study treatment. Blood tests (more than usual), clinical examination and urine tests are part of the safety assessment.

• Additional investigations may be carried out as part of the study, for research purposes for which consent will be sought form the patient, such as additional blood samples and additional scans (CT thorax, abdomen and pelvis).

2. Phase 1 trial of Pembrolizumab: Patients will be carefully monitored for toxicity throughout the trial. A phase I trial has already been conducted to determine the maximum tolerated dose (MTD) of pembrolizumab in bladder cancer. To date no MTD has been defined and the maximum dose tested showed acceptable toxicity and positive effects on reducing tumour size. This study will assess two dose levels of pembrolizumab: 100mg and 200mg and differing radiotherapy doses (24-30Gy in 4-6f). Dose escalation will only occur if the current cohort have shown no signs of unacceptable toxicity at 6 weeks after completing radiotherapy.

3. Recruitment

Participants will be offered information about this study by their clinical teams if they are considered to meet the entry criteria and express interest in taking part in an experimental study. It will be made clear that the study is experimental in nature and that there will not necessarily be a therapeutic benefit from taking part in the study. It will also be made clear that, should patients decide not to take part their future care will not be affected. Patients will be given sufficient time and information to make an informed decision about entering the trial, and not less than 24 hours; all patients entering the trial will give written informed consent. Inclusion and exclusion criteria for this study are standard for a phase 1 trial of a new oncology drug.

4. Confidentiality

Patients will be linked to a unique identifier the code for which will be held on a password protected database held only by the study team. Blood samples, tumour sample processing and other data analysis will take place at the laboratories of Royal Marsden and Institute of Cancer Research in London or Sutton. Sample processing will take place using the study number only. No other patient identifiable information will be available on study samples. Investigators will have access to patient identifiable information on password protected NHS hospital notes and databases only.

5. Conflict of Interest

Patients may be recruited to the study by those involved in their prior clinical care. The investigators do not expect conflict of interest between research and healthcare duties for a number of reasons: patients must give their full informed consent before entering the study, specifically regarding the unknown efficacy of the study drug and the intensive nature of the study. Those patients who do not continue in the study will maintain a relationship with the clinical team if required for symptom control. At the end of the study, patients will be able to access the results if they wish, through the Royal Marsden Website or contact the study team directly.

6. Use of tissue samples in future research

If participants give their consent, any leftover blood or tissue samples which are not required for this study will be stored for future unspecified research in line with the human tissue act regulations. Access and use of samples for research purposes will require appropriate ethical approval. Future researchers will not be able to identify individual patients from their biobank data, demographic and clinical information will be available. ;

Related Conditions & MeSH terms

• Invasive Bladder Cancer
• Urinary Bladder Neoplasms

• NCT number: NCT02560636
• Study type: Interventional
• Source: Royal Marsden NHS Foundation Trust
• Contact: Sijy Pillai
• Phone: +44 (0) 20 8915 6666
• Email: Plummb.Trial@rmh.nhs.uk
• Status: Recruiting
• Phase: Phase 1
• Start date: June 2016
• Completion date: June 2024