Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer (PCR-MIB)
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|ClinicalTrials.gov Identifier: NCT02662062|
Recruitment Status : Recruiting
First Posted : January 25, 2016
Last Update Posted : July 3, 2019
This study will enrol patients with maximally resected (via transurethral resection (TURBT) non-metastatic muscle invasive bladder cancer, who either wish to attempt bladder preservation therapy or are ineligible for cystectomy. Patients must have adequate organ function and performance status to receive cisplatin based chemoradiotherapy, and no contraindications to the use of pembrolizumab. The study will enrol 30 patients to be treated with pembrolizumab and radiotherapy.
All patients will be planned to be treated with 64Gy of radiation therapy in 32 fractions over 6 weeks and 2 days. All patients will receive cisplatin 35mg/m2 IV concurrently weekly with radiation therapy for 6 doses total. Pembrolizumab will commence concurrently with radiation and be given 200mg IV every 21 days, continuing until the 12 week cystoscopy and assessment.
Surveillance cystoscopy will be performed 12 weeks after the commencement of chemoradiotherapy, and assess the rate of complete response to therapy. A safety follow up visit will occur 4 and 12 weeks post cystoscopy. From week 31 survival follow up will commence with clinical assessment, cystoscopy and CT staging performed at intervals until 5 years.
The objective of the study is to assess the safety and feasibility of combining pembrolizumab with chemoradiotherapy. The primary endpoint assessed will be safety, as defined by a satisfactorily low rate of unacceptable toxicity (G3-4 adverse events or failure of completion of planned chemotherapy and radiotherapy according to defined parameters). The secondary endpoint will be efficacy, as assessed by complete response rate of the primary tumour at first post chemoradiotherapy cystoscopic assessment. Exploratory analysis will include assessment of tumour histopathological, molecular, genetic and immunological parameters.
It is expected that it will take two years to accrue the required 30 patients.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: Pembrolizumab Drug: Cisplatin Radiation: Radiotherapy||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer|
|Study Start Date :||August 2016|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||January 2024|
Pembrolizumab to be administered via IV 200mg 3 weekly commenced concurrently with chemoradiotherapy, and continuing until 12 week cystoscopy.
200 mg/m2, IV (in the vein) on day 1 every three weeks (Weeks 1, 3, 7, 10, 13, 16 and 19). until progression or unacceptable toxicity develops.
35 mg/m2, IV (in the vein) every week for six weeks.
2.00Gy once daily for 32 fractions, 5 fractions/week over six weeks and two days (a total of 64Gy).
- Number of patients with grade 3 or 4 acute toxicities (excluding grade 3 or 4 urinary toxicities) that are related to study drug, graded according to CTCAE v4.03. [ Time Frame: 19 weeks of treatment with Pembrolizumab ]
- The efficacy of the addition of pembrolizumab to concurrent chemoradiation regimen using the best response achieved, as assessed by cystoscopy at weeks 19 and 31 of the trial (12 and 24 weeks post completion of chemoradiotherapy). [ Time Frame: Week 19 (12 weeks post chemotherapy) and Week 31 (24 weeks post chemotherapy) where cystoscopic examinations take place. ]
- The number of patients to develop metastatic disease (i.e. the rate of metastatic disease), as assessed by CT scan. [ Time Frame: Through study completion, an average of 7 years. ]
- The number of patients having a salvage cystectomy (i.e. the rate of salvage cystectomy), as assessed by cystoscopy. [ Time Frame: Through study completion, an average of 7 years. ]
- The abundance and composition of tumour infiltrating lymphocytes, as assessed by immunohistochemical analysis, of patients pre-treatment tissue samples. [ Time Frame: Through study completion, an average of 7 years. ]Resected tumour specimens will be available from the patients enrolled on the trial. These pre-treatment specimens will be comprehensively profiled for the abundance and composition of tumour infiltrating lymphocytes (CD4, CD8, CD3, CD20 and FoxP3 positive cells) by immunohistochemistry using the state-of-the-art Vectra Automated Imaging system which enables multiplexed immunohistochemical analysis.
- Changes in gene expression in CD3+ cells pre and post-treatment as assessed by RNAseq analysis to assess for gene expression changes associated with immune activation. [ Time Frame: Through study completion, an average of 7 years. ]
- Changes in the immune regulatory molecules OX-40/LAG3/PD1/ICOS on T cell subsets as assessed by flow cytometry. [ Time Frame: Through study completion, an average of 7 years. ]Blood samples collected prior to treatment, at the end of chemoradiotherapy, and after 24 weeks will be collected from the patients on the trial. PBMCs will be isolated using Ficoll, and changes in specific immune subpopulations (number/ratio) determined by multi-parameter FACS. Changes in the immune regulatory molecules OX-40/LAG3/PD1/ICOS on T cell subsets will be assessed by flow cytometry.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02662062
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