Non-muscle Invasive Bladder Cancer (NMIBC)Phase 1/2PemBlaNCT03167151
Pembrolizumab in Intermediate Risk Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)
A Phase 1/2 study testing Pembrolizumab in people with Non-muscle Invasive Bladder Cancer (NMIBC), run by University of Oxford at 3 sites in United Kingdom.
Trial summary
A parallel group, open label, multi-centre, phase I/II marker-lesion study of intravesical or intravenous pembrolizumab in recurrent intermediate risk NMIBC. Thirty patients (fifteen in each of two arms) will be randomised 1:1 to treatment with either intravesical pembrolizumab (Arm A) or intravenous pembrolizumab… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-muscle Invasive Bladder Cancer (NMIBC)
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 2 Mar 2018to 26 Jun 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible for participation in this trial, the subject must:
- Be willing and able to provide written informed consent for the trial and comply with the protocol scheduled follow-up visits and examinations for the duration of the study.
- Be ≥ 18 years of age on day of signing informed consent.
- Have recurrent NMIBC for which adjuvant treatment post TURBT would be a reasonable treatment option.
- Main study only: a. Have recurrent, multiple (minimum 2) tumours consistent with NMIBC.
- Have at least one lesion of between 5-10mm in size clinically that can be left un-resected at TURBT as the marker lesion.
Show all 14Show fewer
- Have histologically confirmed low grade transitional cell NMIBC at original and any subsequent diagnosis.
- Have a normal upper urinary tract (as evidenced by ultrasound or CT urography within 2 years prior to randomisation) and no evidence of tumour in prostatic urethra at flexible cystoscopy.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Have adequate organ function as defined below:
- Haemoglobin (Hb) ≥ 9 g/dL without transfusion or erythropoietin (EPO) dependency Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) or direct bilirubin < ULN for subjects with total bilirubin levels > 1.5 x ULN Serum alanine aminotransferase (ALT) and/or serum aspartate aminotransferase (AST) ≤ 2.5 x ULN Serum creatinine OR Measured or calculated creatinine clearance ≤ 1.5 x ULN OR
- ≥ 60ml/min for subject with creatinine levels > 1.5 x institutional ULN Albumin ≥ 25g/L International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or APTT is within therapeutic range of intended use of anticoagulants a Creatinine clearance should be calculated as per institutional standard
- Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Both male and female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in section 5.1 for the course of the study and until 120 days after the last dose of the study medication.
Who cannot join
- The subject must be excluded from participating in the trial if the subject:
- Has received prior radiotherapy to the pelvis.
- Has significant urinary incontinence or known bladder instability.
- Main study only:
- Has more than 2 out of 3 of the following present at the current time: i. ≥8 tumours ii. Tumour ≥3cm in size iii. Frequent recurrence (>1/year)
- Has a previous history of any of the following: T1 tumour, high grade/G3 tumour, carcinoma in situ, multiple recurrent large (>3cm) Ta, G1 or G2 tumours.
Show all 27Show fewer
- Had a primary tumour of unknown pathological stage or grade.
- Has disease for which resection of all visible tumours is not possible.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of trial treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Subjects requiring use of inhaled or intranasal corticosteroids or local steroid injections would not be excluded.
- Has a known history of active tuberculosis (TB).
- Has received intravesical Bacillus Calmette-Guerin (BCG) treatment within 30 days prior to the first dose of trial treatment.
- Has hypersensitivity to pembrolizumab or any of its excipients.
- Has had treatment with any other anti-cancer monoclonal antibody within 28 days prior to enrolment or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had treatment with prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of administration of study drug or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurological symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for a t least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active or intractable infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through to 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death ligand 1 (anti PD-L1), or anti-programmed death ligand 2 (anti-PD-L2) agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. hepatitis C virus [HCV] RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Royal Surrey County Hospital NHS Foundation Trust
Guildford, Surrey, GU2 7XX
Oxford University Hospitals NHS Foundation Trust
Oxford, Oxfordshire, OX3 9DU
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, SO16 6YD
About this study
Official title: A Parallel Group Phase I/II Marker Lesion Study to Assess the Safety, Tolerability and Efficacy of Intravenous or Intravesical Pembrolizumab in Intermediate Risk Recurrent Non-muscle Invasive Bladder Cancer
A parallel group, open label, multi-centre, phase I/II marker-lesion study of intravesical or intravenous pembrolizumab in recurrent intermediate risk NMIBC. Thirty patients (fifteen in each of two arms) will be randomised 1:1 to treatment with either intravesical pembrolizumab (Arm A) or intravenous pembrolizumab (Arm B). The main study will be preceded by a single institution safety run-in phase involving intra-patient dose escalation in six patients to confirm the safety and tolerability of intravesical pembrolizumab and the dose to be used in the randomised phase.
Read the detailed description
Bladder cancer is the seventh most common cancer in the United Kingdom (UK) and ninth most common cancer worldwide. New strategies for treating this disease are urgently required to reduce recurrence and progression rates. Pembrolizumab is a type of immunotherapy drug that has been approved for use in certain types of melanoma and lung cancer. It is thought to work by helping the body's immune system to recognise and attack cancer. Drugs that work in a similar way have shown some encouraging results in studies treating patients with bladder cancer that has spread to other parts of the body, although they are not currently approved for treating either advanced or localised bladder cancer.
This trial is being performed to assess the safety and tolerability of giving pembrolizumab to patients with localised bladder cancer and to study what effects the drug has on the tumour; Participants will have all but one tumour (referred to as the marker lesion) removed during their transurethral resection of bladder tumour (TURBT) procedure at the start of the trial. After trial treatment, a further TURBT procedure will be carried out to remove the marker lesion, or if the marker lesion is no longer visible, a biopsy will be taken of the area where the growth was before.
After a safety run in with intra-patient dose escalation of intravesical pembrolizumab performed in paired patient cohorts, the trial will test two different ways of giving the pembrolizumab; directly into the bladder (intravesical) with 6 doses being received over 6 weeks and with a further dose approximately 3 weeks later, or into the blood stream via the veins (intravenous) with a dose being received every 3 weeks for a maximum of 4 doses.
36 eligible participants from across 3 UK centres will be randomly allocated to receive treatment by one of these ways. Following the end of treatment visit, patients will return to receiving standard care but receive follow-up for up to 2 years.
- Being tested
- Pembrolizumab
- Keywords
- Recurrent intermediate risk NMIBC, Intravesical Pembrolizumab, Intravenous Pembrolizumab, Phase I/II, Marker-lesion, Non-muscle invasive bladder cancer (NMIBC)
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Solution for Infusion (Intravesical and Intravenous) 100mg/ 4ml vial
| Study group | Role | What they receive |
|---|---|---|
| Arm A Intravesical | Experimental | Intravesical Pembrolizumab (solution for infusion) 50-200 mg, given on D1, D8, D15, D22, D29, D36 \& D64.
Dose to be decided after safety run-in. Receives: Drug: Pembrolizumab |
| Arm B Intravenous | Active comparator | Intravenous Pembrolizumab (solution for infusion), 200mg, given on D1, D22, D43, D64 Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose Limiting Toxicities (DLTs) to Assess the Safety, Tolerability and Toxicities of Intravesical Pembrolizumab After Transurethral Resection of Bladder Tumour (TURBT).
Adverse events are categorised according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Patients with intermediate risk Non-muscle Invasive Bladder Cancer (NMIBC) were assessed for dose limiting toxicity (DLT) and tolerability.
Administration of at least 5 out of 6 treatments was required for the regime to be defined as tolerable.
Measured: Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start2 Mar 2018
- Primary completion26 Mar 2019
- Study completion26 Jun 2019
Why it stopped: The study failed to recruit within the permitted timeframe
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-muscle Invasive Bladder Cancer (NMIBC)Studies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Andrew S Protheroe, MRCP, FRCP, Principal investigator, Oxford University Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03167151
- Sponsor's protocol ID
- OCTO-079
- Other IDs
- 2016-002267-33, 2016
- Acronym
- PemBla
- Status last verified
- Dec 2019
- First submitted
- 2 May 2017
- Last updated
- 31 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Parallel Group Phase I/II Marker Lesion Study to Assess the Safety, Tolerability and Efficacy of Intravenous or Intravesical Pembrolizumab in Intermediate Risk Recurrent Non-muscle Invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT03167151
- Acronym / sponsor ID
- PemBla / OCTO-079
- Keywords
- Recurrent intermediate risk NMIBC, Intravesical Pembrolizumab, Intravenous Pembrolizumab, Phase I/II, Marker-lesion, Non-muscle invasive bladder cancer (NMIBC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study failed to recruit within the permitted timeframe
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 2 Mar 2018 (actual)
- Primary completion
- 26 Mar 2019 (actual)
- Study completion
- 26 Jun 2019 (actual)
- First posted
- 25 May 2017 (actual)
- Results
- Posted 31 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A parallel group, open label, multi-centre, phase I/II marker-lesion study of intravesical or intravenous pembrolizumab in recurrent intermediate risk NMIBC. Thirty patients (fifteen in each of two arms) will be randomised 1:1 to treatment with either intravesical pembrolizumab (Arm A) or intravenous pembrolizumab (Arm B). The main study will be preceded by a single institution safety run-in phase involving intra-patient dose escalation in six patients to confirm the safety and tolerability of intravesical pembrolizumab and the dose to be used in the randomised phase.
Detailed description
Bladder cancer is the seventh most common cancer in the United Kingdom (UK) and ninth most common cancer worldwide. New strategies for treating this disease are urgently required to reduce recurrence and progression rates. Pembrolizumab is a type of immunotherapy drug that has been approved for use in certain types of melanoma and lung cancer. It is thought to work by helping the body's immune system to recognise and attack cancer. Drugs that work in a similar way have shown some encouraging results in studies treating patients with bladder cancer that has spread to other parts of the body, although they are not currently approved for treating either advanced or localised bladder cancer.
This trial is being performed to assess the safety and tolerability of giving pembrolizumab to patients with localised bladder cancer and to study what effects the drug has on the tumour; Participants will have all but one tumour (referred to as the marker lesion) removed during their transurethral resection of bladder tumour (TURBT) procedure at the start of the trial. After trial treatment, a further TURBT procedure will be carried out to remove the marker lesion, or if the marker lesion is no longer visible, a biopsy will be taken of the area where the growth was before.
After a safety run in with intra-patient dose escalation of intravesical pembrolizumab performed in paired patient cohorts, the trial will test two different ways of giving the pembrolizumab; directly into the bladder (intravesical) with 6 doses being received over 6 weeks and with a further dose approximately 3 weeks later, or into the blood stream via the veins (intravenous) with a dose being received every 3 weeks for a maximum of 4 doses.
36 eligible participants from across 3 UK centres will be randomly allocated to receive treatment by one of these ways. Following the end of treatment visit, patients will return to receiving standard care but receive follow-up for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A Intravesical | Experimental | Drug: PembrolizumabIntravesical Pembrolizumab (solution for infusion) 50-200 mg, given on D1, D8, D15, D22, D29, D36 \& D64. Dose to be decided after safety run-in. |
| Arm B Intravenous | Active comparator | Drug: PembrolizumabIntravenous Pembrolizumab (solution for infusion), 200mg, given on D1, D22, D43, D64 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Be willing and able to provide written informed consent for the trial and comply with the protocol scheduled follow-up visits and examinations for the duration of the study.
- Be ≥ 18 years of age on day of signing informed consent.
- Have recurrent NMIBC for which adjuvant treatment post TURBT would be a reasonable treatment option.
- Main study only: a. Have recurrent, multiple (minimum 2) tumours consistent with NMIBC.
- Have a normal upper urinary tract (as evidenced by ultrasound or CT urography within 2 years prior to randomisation) and no evidence of tumour in prostatic urethra at flexible cystoscopy.
Key exclusion criteria (27 listed)
- Has received prior radiotherapy to the pelvis.
- Has significant urinary incontinence or known bladder instability.
- Main study only:
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of trial treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Subjects requiring use of inhaled or intranasal corticosteroids or local steroid injections would not be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaSolution for Infusion (Intravesical and Intravenous) 100mg/ 4ml vial | Drug | Arm A Intravesical, Arm B Intravenous |
Primary outcome
Number of Dose Limiting Toxicities (DLTs) to Assess the Safety, Tolerability and Toxicities of Intravesical Pembrolizumab After Transurethral Resection of Bladder Tumour (TURBT).
Time frame: Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy.
Adverse events are categorised according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Patients with intermediate risk Non-muscle Invasive Bladder Cancer (NMIBC) were assessed for dose limiting toxicity (DLT) and tolerability. Administration of at least 5 out of 6 treatments was required for the regime to be defined as tolerable.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Non-muscle Invasive Bladder Cancer (NMIBC)
RecruitingPhase 1
A Study to Learn About the Study Medicine PF-08052667 in People With Bladder Cancer
Non-muscle Invasive Bladder Cancer
Recruiting
Using Urine Tumor DNA to De-Intensify Surveillance in Non-Muscle Invasive Bladder Cancer
Non-muscle Invasive Bladder Cancer (NMIBC)
Active, not recruitingPhase 3
A Study of TAR-200 Versus Intravesical Chemotherapy in Participants With Recurrent High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC) After Bacillus Calmette-Guérin (BCG)
Non-Muscle Invasive Bladder Neoplasms
RecruitingPhase 2
Disitamab Vedotin Plus Intravesical Mitomycin C in HER2-Expressing Intermediate- to High-Risk Non-Muscle-Invasive Bladder Cancer
Non-Muscle-Invasive Bladder Cancer (NMIBC)
RecruitingPhase 3
A Study to Evaluate TAR-210 Versus Single Agent Intravesical Cancer Treatment in Participants With Bladder Cancer
Non-Muscle Invasive Bladder Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew S Protheroe, MRCP, FRCP principal investigator
Oxford University Hospitals NHS Trust
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pembrolizumab in people with Non-muscle Invasive Bladder Cancer (NMIBC), run by University of Oxford at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Dose Limiting Toxicities (DLTs) to Assess the Safety, Tolerability and Toxicities of Intravesical Pembrolizumab After Transurethral Resection of Bladder Tumour (TURBT). (time frame: Adverse event monitoring starts on the day of the TURBT procedure (Day -14) until 90 days post treatment, or 30 days following administration of the last dose of study medication if the subject initiates a new anticancer therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.