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NCT02662062: PCR-MIB

Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer

Completed Phase 2 Results posted Last updated 27 January 2025
What this trial tests

Phase 2 trial testing Pembrolizumab in Bladder Cancer in 28 participants. Completed in 26 August 2024.

Timeline
11 July 2017
Primary endpoint
12 May 2022
26 August 2024

Quick facts

Lead sponsorAustralian and New Zealand Urogenital and Prostate Cancer Trials Group
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment28
Start date11 July 2017
Primary completion12 May 2022
Estimated completion26 August 2024
Sites7 locations across Australia

Drugs / interventions tested

Conditions studied

Sponsor

Australian and New Zealand Urogenital and Prostate Cancer Trials Group — full company profile →

Who can join

18 and older, any sex, with Bladder Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

The Number of Participants Experiencing an Unacceptable Level of Toxicity as Defined Below Primary · 12 weeks of study treatment

Unacceptable toxicity was predefined as fitting one of the following categories. * Grade 3 or worse adverse event per CTCAE V 5.0 (excluding urinary adverse events Grade 3 and Grade 4) * Cisplatin is withheld for 2 or more doses * Cisplatin is withheld or dose reduced such that \<66% of the intended total cisplatin dose is delivered * Radiation therapy extended beyond 7 weeks * Any single pembrolizumab dose is delayed for \>6 weeks

Unacceptable toxicity - total
GroupValue95% CI
Pembrolizumab9
Grade 3 or higher adverse event
GroupValue95% CI
Pembrolizumab6
Immune mediated toxicity meeting unacceptable toxicity definition.
GroupValue95% CI
Pembrolizumab2
Cisplatin dose omissions 2 or greater
GroupValue95% CI
Pembrolizumab4
Radiation duration >7 weeks
GroupValue95% CI
Pembrolizumab2
Pembrolizumab >6 weeks delay
GroupValue95% CI
Pembrolizumab1
Complete Response Rate at Week 19 of the Trial (12 Weeks Post Completion of Chemoradiotherapy). Secondary · Week 19 (12 weeks post chemotherapy)

Complete response defined at this time point by fulfillment of all of the following criteria: i) the bi-manual examination under anesthesia is negative (performed at the time of cystoscopy) ii) All biopsies are negative for any tumor at the site(s) of pre-treatment tumor(s) iii) There is an absence of metastatic disease on most recently performed imaging of chest/abdomen and pelvis

GroupValue95% CI
Pembrolizumab9070 – 99
The Complete Response Rate Assessed at Week 31 of the Trial (24 Weeks Post Completion of Chemoradiotherapy). Secondary · Week 31 of the trial (24 weeks post completion of chemoradiotherapy)

Complete response defined at this time point by fulfillment of all of the following criteria: i) the bi-manual examination under anesthesia is negative (performed at the time of cystoscopy) ii) All biopsies are negative for any tumor at the site(s) of pre-treatment tumor(s) iii) There is an absence of metastatic disease on most recently performed imaging of chest/abdomen and pelvis

GroupValue95% CI
Pembrolizumab8870 – 98
Estimated Median Overall Survival Secondary · median follow up 39 months

Estimation after characterization with a Kaplan Meier curve

GroupValue95% CI
Pembrolizumab3917 – NA
Overall Survival at 12 Months Post Study Entry Secondary · 12 months post study entry

Overall survival timepoint estimated after characterization on a Kaplan Meier curve

GroupValue95% CI
Pembrolizumab9272 – 98
Distant Metastasis Free Survival (DMFS) at 12 Months Secondary · At 12 months post study entry

End point was characterized using a Kaplan Meier curve and 12 month time point assessed.

GroupValue95% CI
Pembrolizumab8564 – 94
Local Disease Free Survival (LRPFS) at 12 Months Secondary · 12 months post therapy commencement

Local recurrence was defined as recurrence in the bladder or a nodal recurrence in the pelvis

GroupValue95% CI
Pembrolizumab8868 – 98

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected over the period of enrollment in the study (Planned out to 5 years post commencement) the median follow up at the conclusion of the trial was 39 months. Reporting threshold: 3.5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab
Serious: 13/28 (46%)
Deaths: 8/28

Serious adverse events (20 terms)

ReactionSystemPembrolizumab
Urinary tract infectionInfections and infestations
HaematuriaRenal and urinary disorders
FeverGeneral disorders
Renal and urinary discorders (other)Renal and urinary disorders
Musculoskeletal and Conncective tissue disorder (other)Musculoskeletal and connective tissue disorders
HypetensionVascular disorders
Cystitis noninfectiveRenal and urinary disorders
Infusion related reactionProduct Issues
Metabolism and nutritional disorder (other)Metabolism and nutrition disorders
DelusionsPsychiatric disorders
FractureMusculoskeletal and connective tissue disorders
infections and infestations (other)Infections and infestations
DiarrhoeaGastrointestinal disorders
FallGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Heart FailureCardiac disorders
Nervous system disorders - otherNervous system disorders
HypothyroidismEndocrine disorders
Acute Kidney InjuryRenal and urinary disorders
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Other adverse events (34 terms — click to expand)

ReactionSystemPembrolizumab
FatigueGeneral disorders
Urinary frequencyRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
ConstipationGastrointestinal disorders
HaematuriaRenal and urinary disorders
Rash MaculopapularSkin and subcutaneous tissue disorders
Cystitis NoninfectiveRenal and urinary disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
HypothyroidismEndocrine disorders
ChillsGeneral disorders
Oedema LimbsSkin and subcutaneous tissue disorders
Platelet Count DecreasedBlood and lymphatic system disorders
Alanine Aminotransferase IncreasedGastrointestinal disorders
Urinary Tract PainRenal and urinary disorders
FeverGeneral disorders
Urinary IncontinenceRenal and urinary disorders
Dry skinSkin and subcutaneous tissue disorders
Gastro-oesophageal reflux diseaseGastrointestinal disorders
InsomniaGeneral disorders
ParasthesiaNervous system disorders
TinnitusNervous system disorders
Urinary UrgencyRenal and urinary disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
FallGeneral disorders
Abdominal PainGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Creatinine increasedRenal and urinary disorders
HeadacheGeneral disorders
HyperthyroidismEndocrine disorders
Mucositis OralGastrointestinal disorders
Weight lossGeneral disorders
HypertensionVascular disorders
Neutrophil count decreasedBlood and lymphatic system disorders

Most-reported serious reactions: Urinary tract infection, Haematuria, Fever, Renal and urinary discorders (other), Musculoskeletal and Conncective tissue disorder (other), Hypetension, Cystitis noninfective, Infusion related reaction.

Data from ClinicalTrials.gov NCT02662062 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current clinical trials testing the combination of immunotherapy with radiotherapy.
    Kang J, Demaria S, Formenti S. · · 2016 · cited 293× · PMID 27660705 · DOI 10.1186/s40425-016-0156-7
  2. PD1/PDL1 inhibitors for the treatment of advanced urothelial bladder cancer.
    Stenehjem DD, Tran D, Nkrumah MA, Gupta S. · · 2018 · cited 94× · PMID 30275703 · DOI 10.2147/ott.s135157
  3. Trial Watch: Immunotherapy plus radiation therapy for oncological indications.
    Vacchelli E, Bloy N, Aranda F, Buqué A, et al · · 2016 · cited 61× · PMID 27757313 · DOI 10.1080/2162402x.2016.1214790
  4. Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response.
    Daro-Faye M, Kassouf W, Souhami L, Marcq G, et al · · 2021 · cited 45× · PMID 32915313 · DOI 10.1007/s00345-020-03440-4
  5. Improving Anti-PD-1/PD-L1 Therapy for Localized Bladder Cancer.
    de Jong FC, Rutten VC, Zuiverloon TCM, Theodorescu D. · · 2021 · cited 40× · PMID 33802033 · DOI 10.3390/ijms22062800
  6. Trimodality therapy for bladder cancer: modern management and future directions.
    Pham A, Ballas LK. · · 2019 · cited 32× · PMID 30855374 · DOI 10.1097/mou.0000000000000601
  7. Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions.
    Gupta S, Gill D, Poole A, Agarwal N. · · 2017 · cited 29× · PMID 28134806 · DOI 10.3390/cancers9020015
  8. Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical trials.
    Johnson CB, Win SY. · · 2018 · cited 26× · PMID 29632719 · DOI 10.1080/2162402x.2017.1408744

Verify or expand the search:

Other trials of Pembrolizumab

Trials testing the same drug.

Other recruiting trials for Bladder Cancer

Currently open trials in the same condition.

Other Australian and New Zealand Urogenital and Prostate Cancer Trials Group trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02662062.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing