Muscle-invasive Transitional Cell Carcinoma of the BladderPhase 1NCT02723838
Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder
A Phase 1 study testing REOLYSIN®, Gemcitabine and Cisplatin in people with Muscle-invasive Transitional Cell Carcinoma of the Bladder, run by Oncolytics Biotech.
Trial summary
The purpose of this study is to investigate the safety and efficacy of intratumoral REOLYSIN® therapy alone and in combination with standard neoadjuvant gemcitabine and cisplatin in muscle-invasive bladder cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Muscle-invasive Transitional Cell Carcinoma of the Bladder
- What is being tested?
- REOLYSIN®, Gemcitabine and Cisplatin
- Type of treatment
- Injection or infusion
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 28 Feb 2017to 28 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph nodes involvement (N1-2) in Stage III and IV (M0).
- ECOG performance status ≤2.
- Adequate liver function with a bilirubin within normal limits. Transaminases up to 3 x ULN (Grade 1) and alkaline phosphatase may be up to 2.5 x ULN (Grade 1).
- Adequate bone marrow function, as defined by neutrophils count of ≥1,500/mm3, and platelet count ≥100,000/ mm3.
- Adequate renal function (serum creatinine ≤1.5 times the ULN).
- Negative pregnancy test and reliable and appropriate contraceptive method during the study for a woman of childbearing potential. All female patients of childbearing age and all male patients with partners of childbearing age should use a reliable method of contraception, such as the barrier method, throughout the study and for 60 days after last treatment.
- Informed of the investigational nature of this study and must sign a written informed consent in accordance with institutional and federal guidelines.
Who cannot join
- Received any prior therapy for invasive bladder cancer including surgery, radiation therapy, chemotherapy or any other systemic anti-cancer therapy (prior intravesical therapy for non-invasive bladder cancer is acceptable including intravesical BCG and/or mitomycin and interferon).
- Evidence of lymph nodes or other metastatic disease beyond the pelvis (N3 and/or M1).
- Pre-existing immunosuppressive or connective tissue disorders that require immune suppressive drugs.
- History of HIV or active hepatitis.
- Any serious concurrent illness including; but not limited to, unstable angina pectoris, uncompensated congestive cardiac failure; myocardial infarct in the previous 6 months; cardiac arrhythmias or psychiatric illness that would limit compliance with study requirements.
- Pregnant or lactating.
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- A history of hypersensitivity to gemcitabine and cisplatin or any component of the formulation.
- A prior malignancy, other than non-melanoma skin cancer, unless they have completed therapy at least 5 years prior to start of study and have no evidence of recurrent or residual disease.
- Unwilling or unable to sign informed consent document.
- In social situations that would limit compliance with study requirements.
About this study
Official title: A Phase 1b Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder
The purpose of this study is to investigate the safety and efficacy of intratumoral REOLYSIN® therapy alone and in combination with standard neoadjuvant gemcitabine and cisplatin in muscle-invasive bladder cancer.
Read the detailed description
Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous, non-enveloped human reovirus. Reovirus has been shown to replicate selectively in Ras-transformed cells causing cell lysis. Activating mutations in Ras or mutations in oncogenes signaling through the Ras pathway may occur in as many as 80% of human tumors. The specificity of the reovirus for Ras-transformed cells, coupled with its relatively nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate.
This is an open-label study of intratumoral REOLYSIN® in combination with standard of care neoadjuvant cisplatin/gemcitabine in patients with histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph node involvement (N1-2) in Stage III and IV with no distant metastases (M0) and no prior systemic therapy for bladder cancer.
Treatment with intratumoral REOLYSIN® and chemotherapy is planned for 3 cycles followed by radical cystectomy or until unacceptable toxicity or another discontinuation criterion is met.
Two sequential treatment cohorts will be enrolled.
Patients in Cohort 1 will receive intratumoral REOLYSIN® on Cycle 1 Day 1, then 7-14 days later patients will receive intratumoral REOLYSIN® on Cycle 2 Day 1 plus intravenous neoadjuvant chemotherapy for 2 cycles (every 3 weeks) starting from Cycle 2 Day 2 followed by radical cystectomy. Three patients will be enrolled in this cohort. If there is a Dose Limiting Toxicity the cohort will be expanded to an additional 3 patients.
Upon completion of Cohort 1, Cohort 2 will be open to enrollment of 3 patients to receive 3 cycles of standard neoadjuvant chemotherapy on Day 1 and Day 8 of each cycle and intratumoral REOLYSIN® on Day 2 of each cycle (every 3 weeks). If there is a Dose Limiting Toxicity the cohort will be expanded to an additional 3 patients.
An Expansion Cohort will follow with up to 12 patients to be enrolled following either Cohort 1 or Cohort 2 treatment regimen based on the results of Cohort 1 and Cohort 2.
- Being tested
- REOLYSIN®, Gemcitabine, Cisplatin
- Keywords
- Bladder, Cancer, REOLYSIN®, Gemcitabine, Cisplatin, Reovirus, Oncolytic virus
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REOLYSIN®Biological
3 cycles (each cycle = 21 days). Cohort 1: 3x10E10 TCID50 intratumoral via cystoscopy on Day 1 of each cycle. Cohort 2: 3x10E10 TCID50 intratumoral via cystoscopy on Day 2 of each cycle.
GemcitabineDrug
3 cycles (each cycle = 21 days). Cohort 1: 1000mg/m2 intravenously on Day 2 and Day 9 of Cycle 2 and Cycle 3. Cohort 2: 1000mg/m2 intravenously on Day 1 and Day 8 of each cycle.
CisplatinDrug
3 cycles (each cycle = 21 days). Cohort 1: 70 mg/m2 intravenously on Day 2 of Cycle 2 and Cycle 3. Cohort 2: 70 mg/m2 intravenously on Day 1 of each cycle.
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Nature, frequency, severity and timing of Adverse Events.
Measured: During treatment and up to 28 days after treatment
Pre- and post-treatment biopsies will be evaluated for tumor viability, percentage of necrosis, reovirus replication and tumor infiltration of immune cells and expression of PD-1 and PD-L1
Measured: Assessed at surgery conducted following 3 3-week study treatment cycles
Secondary outcomes (2)
Time to Treatment Failure (TTF)
Measured: By medical chart review until disease reoccurrence or 2 years from surgery, whichever occurs first first.
Disease Free Survival (DFS)
Measured: By medical chart review until disease reoccurrence or death or 2 years from surgery, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2016 (estimated)
- Study start28 Feb 2017 (estimated)
- Primary completion30 Sep 2017 (estimated)
- Study completion28 Feb 2018 (estimated)
Why it stopped: Company has reprioritized clinical plans to focus on later-stage studies.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle-invasive Transitional Cell Carcinoma of the BladderStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncolytics Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02723838
- Sponsor's protocol ID
- REO 023
- Status last verified
- Mar 2017
- First submitted
- 24 Mar 2016
- Last updated
- 7 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder
- ClinicalTrials.gov ID
- NCT02723838
- Acronym / sponsor ID
- REO 023
- Keywords
- Bladder, Cancer, REOLYSIN®, Gemcitabine, Cisplatin, Reovirus, Oncolytic virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Company has reprioritized clinical plans to focus on later-stage studies.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Oncolytics BiotechIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2017 (estimated)
- Primary completion
- 30 Sep 2017 (estimated)
- Study completion
- 28 Feb 2018 (estimated)
- First posted
- 31 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the safety and efficacy of intratumoral REOLYSIN® therapy alone and in combination with standard neoadjuvant gemcitabine and cisplatin in muscle-invasive bladder cancer.
Detailed description
Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous, non-enveloped human reovirus. Reovirus has been shown to replicate selectively in Ras-transformed cells causing cell lysis. Activating mutations in Ras or mutations in oncogenes signaling through the Ras pathway may occur in as many as 80% of human tumors. The specificity of the reovirus for Ras-transformed cells, coupled with its relatively nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate.
This is an open-label study of intratumoral REOLYSIN® in combination with standard of care neoadjuvant cisplatin/gemcitabine in patients with histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph node involvement (N1-2) in Stage III and IV with no distant metastases (M0) and no prior systemic therapy for bladder cancer.
Treatment with intratumoral REOLYSIN® and chemotherapy is planned for 3 cycles followed by radical cystectomy or until unacceptable toxicity or another discontinuation criterion is met.
Two sequential treatment cohorts will be enrolled.
Patients in Cohort 1 will receive intratumoral REOLYSIN® on Cycle 1 Day 1, then 7-14 days later patients will receive intratumoral REOLYSIN® on Cycle 2 Day 1 plus intravenous neoadjuvant chemotherapy for 2 cycles (every 3 weeks) starting from Cycle 2 Day 2 followed by radical cystectomy. Three patients will be enrolled in this cohort. If there is a Dose Limiting Toxicity the cohort will be expanded to an additional 3 patients.
Upon completion of Cohort 1, Cohort 2 will be open to enrollment of 3 patients to receive 3 cycles of standard neoadjuvant chemotherapy on Day 1 and Day 8 of each cycle and intratumoral REOLYSIN® on Day 2 of each cycle (every 3 weeks). If there is a Dose Limiting Toxicity the cohort will be expanded to an additional 3 patients.
An Expansion Cohort will follow with up to 12 patients to be enrolled following either Cohort 1 or Cohort 2 treatment regimen based on the results of Cohort 1 and Cohort 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph nodes involvement (N1-2) in Stage III and IV (M0).
- ECOG performance status ≤2.
- Adequate liver function with a bilirubin within normal limits. Transaminases up to 3 x ULN (Grade 1) and alkaline phosphatase may be up to 2.5 x ULN (Grade 1).
- Adequate bone marrow function, as defined by neutrophils count of ≥1,500/mm3, and platelet count ≥100,000/ mm3.
- Adequate renal function (serum creatinine ≤1.5 times the ULN).
Key exclusion criteria (10 listed)
- Received any prior therapy for invasive bladder cancer including surgery, radiation therapy, chemotherapy or any other systemic anti-cancer therapy (prior intravesical therapy for non-invasive bladder cancer is acceptable including intravesical BCG and/or mitomycin and interferon).
- Evidence of lymph nodes or other metastatic disease beyond the pelvis (N3 and/or M1).
- Pre-existing immunosuppressive or connective tissue disorders that require immune suppressive drugs.
- History of HIV or active hepatitis.
- Any serious concurrent illness including; but not limited to, unstable angina pectoris, uncompensated congestive cardiac failure; myocardial infarct in the previous 6 months; cardiac arrhythmias or psychiatric illness that would limit compliance with study requirements.
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 |
|---|---|---|
| REOLYSIN®3 cycles (each cycle = 21 days). Cohort 1: 3x10E10 TCID50 intratumoral via cystoscopy on Day 1 of each cycle. Cohort 2: 3x10E10 TCID50 intratumoral via cystoscopy on Day 2 of each cycle. | Biological | – |
| Gemcitabine3 cycles (each cycle = 21 days). Cohort 1: 1000mg/m2 intravenously on Day 2 and Day 9 of Cycle 2 and Cycle 3. Cohort 2: 1000mg/m2 intravenously on Day 1 and Day 8 of each cycle. | Drug | – |
| Cisplatin3 cycles (each cycle = 21 days). Cohort 1: 70 mg/m2 intravenously on Day 2 of Cycle 2 and Cycle 3. Cohort 2: 70 mg/m2 intravenously on Day 1 of each cycle. | Drug | – |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: During treatment and up to 28 days after treatment
Nature, frequency, severity and timing of Adverse Events.
Pre- and post-treatment biopsies will be evaluated for tumor viability, percentage of necrosis, reovirus replication and tumor infiltration of immune cells and expression of PD-1 and PD-L1
Time frame: Assessed at surgery conducted following 3 3-week study treatment cycles
2 secondary outcomes
Time to Treatment Failure (TTF)
Time frame: By medical chart review until disease reoccurrence or 2 years from surgery, whichever occurs first first.
Disease Free Survival (DFS)
Time frame: By medical chart review until disease reoccurrence or death or 2 years from surgery, whichever occurs first.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing REOLYSIN®, Gemcitabine and Cisplatin in people with Muscle-invasive Transitional Cell Carcinoma of the Bladder, run by Oncolytics Biotech.
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 7 inclusion and 10 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: withdrawn, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Incidence of Treatment-Emergent Adverse Events (time frame: During treatment and up to 28 days after treatment). The study lists 2 primary outcomes in all. 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 7 Mar 2017.