Condition or disease | Intervention/treatment | Phase |
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Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall Stage II Bladder Cancer AJCC v8 Stage II Renal Pelvis Cancer AJCC v8 Stage II Ureter Cancer AJCC v8 Stage II Urethral Cancer AJCC v8 Stage III Bladder Cancer AJCC v8 Stage III Renal Pelvis Cancer AJCC v8 Stage III Ureter Cancer AJCC v8 Stage III Urethral Cancer AJCC v8 Stage IIIA Bladder Cancer AJCC v8 Stage IIIB Bladder Cancer AJCC v8 Urethral Urothelial Carcinoma | Drug: Avelumab Drug: Cisplatin Drug: Fluorouracil Drug: Mitomycin Other: Quality-of-Life Assessment Radiation: Radiation Therapy | Phase 2 |
PRIMARY OBJECTIVES:
I. To evaluate the complete response rate of concurrent chemotherapy radiation treatment combined with avelumab for patients with muscle invasive bladder cancer.
SECONDARY OBJECTIVES:
I. To evaluate the safety and toxicity (adverse event profile) of concurrent chemotherapy radiation treatment combined with avelumab.
II. To evaluate quality of life (QoL) at 1 year of concurrent chemotherapy radiation treatment combined with avelumab.
III. To evaluate progression-free survival and relapse-free survival at 1 year with concurrent chemotherapy radiation treatment combined with avelumab.
CORRELATIVE OBJECTIVES:
I. To explore biomarkers that may predict response to avelumab in the muscle invasive population.
II. To evaluate the association of tumor mutational burden with response to concurrent chemo- radiation and immunotherapy.
III. To evaluate whether concurrent chemoradiation and immunotherapy after maximal transurethral resection of bladder tumor (TURBT) is associated with a decrease in circulating Bim+CD11a^high PD-1+CD8+ T-cells and myeloid-derived suppressor cells (MDSCs).
OUTLINE:
Participants receive avelumab intravenously (IV) over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants receive either fluorouracil IV on days 1-5 and 16-20 during radiation therapy (RT) and mitomycin IV on day 1 of course 3, or cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 days, 6, 9, and 12 months.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 2 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase II Study Evaluating Combination Chemotherapy + Radiotherapy (RT) With Avelumab in Muscle Invasive Bladder Cancer |
Actual Study Start Date : | September 19, 2018 |
Actual Primary Completion Date : | November 14, 2019 |
Actual Study Completion Date : | July 27, 2020 |
Arm | Intervention/treatment |
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Experimental: Treatment (avelumab, chemotherapy, radiation therapy)
Participants receive avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants receive either fluorouracil IV on days 1-5 and 16-20 during RT and mitomycin IV on day 1 of course 3, or cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
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Drug: Avelumab
Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Fluorouracil Given IV
Other Names:
Drug: Mitomycin Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy Undergo RT
Other Names:
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Patients enrolled will have non-measurable disease based on imaging at baseline. Patients will be assessed for a response after 6 months of treatment using the results of a biopsy and cytology test. A complete response (CR) is defined as having a negative biopsy and negative urine cytology at 6 months from registration after finishing of concurrent RT and immunotherapy. Imaging of abdomen and pelvis confirming no systemic disease within 4 weeks of cystoscopy will be completed.
The proportion of patients reporting a CR is reported here with confidence intervals for the true success proportion using the binomial distribution.
EORTC QLQ-C30 is a 30-item patient-reported questionnaire. 28 of the 30 items are measured on a 1-4 scale (1=not at all; 4=very much) with the remaining two items (overall health and overall quality of life) scored on a 1-7 numeric analogue scale (1=very poor; 7=excellent). The recall period for the EORTC QLQ-C30 is one week.
Changes from baseline will be statistically tested using paired t-tests, and standardized response means (mean of the change from baseline scores at a given cycle, divided by the standard deviation of the change scores) will be interpreted (after applying Middel's (2002) adjustment) using Cohen's (1988) cut-offs: <0.20 = trivial; 0.20-<0.50 = small; 0.50-<0.80 = moderate; and >=/0.80 = large. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.
EORTC QLQ-BLM30 is a 30-item questionnaire for patients with muscle invasive bladder cancer (T2, T3, T4a and T4b). The muscle-invasive bladder cancer module contains additional items assessing urostomy problems, problems associated with the use of a catheter, and body image.
Changes from baseline will be statistically tested using paired t-tests, and standardized response means (mean of the change from baseline scores at a given cycle, divided by the standard deviation of the change scores) will be interpreted (after applying Middel's (2002) adjustment) using Cohen's (1988) cut-offs: <0.20 = trivial; 0.20-<0.50 = small; 0.50-<0.80 = moderate; and >=/0.80 = large. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.
Recurrence-free survival is defined as the time from registration to the time of recurrence or death. Recurrence is defined as having histologically proven first appearance of muscle invasive bladder cancer, clinical evidence of metastatic disease, or treatment with radical cystectomy or radiation to the bladder, or death due to any cause after they were confirmed remission at 6 month evaluation.
The median time will be estimated using the method of Kaplan-Meier.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Patients with locally advanced unresectable (T4b) or metastatic urothelial carcinoma (N1M0-1) as assessed on baseline radiographic imaging obtained =< 70 days prior to study registration. The required radiographic imaging includes:
Patients with concurrent urothelial carcinoma and/or related variants anywhere outside bladder
A prior or concurrent malignancy of any other site or histology unless the patient has been disease-free for > 2 years prior to registration except for:
Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies =< 4 weeks prior to registration, or who have not recovered from the side effects of such therapy.
Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 4 weeks prior to registration, or who have not recovered from side effects of such procedure or injury prior to registration.
Clinically significant cardiac diseases, including any of the following:
History of untreated human immunodeficiency virus (HIV)
History of active hepatitis B infection
Known diagnosis of any condition (i.e. post-hematopoietic or organ transplant, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy.
United States, Arizona | |
Mayo Clinic in Arizona | |
Scottsdale, Arizona, United States, 85054 | |
United States, Florida | |
Mayo Clinic in Florida | |
Jacksonville, Florida, United States, 32224 | |
United States, Minnesota | |
Mayo Clinic | |
Rochester, Minnesota, United States, 55905 |
Principal Investigator: | Parminder Singh | Mayo Clinic |
Tracking Information | |||||||
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First Submitted Date ICMJE | July 26, 2018 | ||||||
First Posted Date ICMJE | August 7, 2018 | ||||||
Results First Submitted Date ICMJE | October 28, 2020 | ||||||
Results First Posted Date ICMJE | February 21, 2021 | ||||||
Last Update Posted Date | April 8, 2021 | ||||||
Actual Study Start Date ICMJE | September 19, 2018 | ||||||
Actual Primary Completion Date | November 14, 2019 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Proportion of Participants With Complete Response (At 6 Months) [ Time Frame: At 6 months from registration ] Patients enrolled will have non-measurable disease based on imaging at baseline. Patients will be assessed for a response after 6 months of treatment using the results of a biopsy and cytology test. A complete response (CR) is defined as having a negative biopsy and negative urine cytology at 6 months from registration after finishing of concurrent RT and immunotherapy. Imaging of abdomen and pelvis confirming no systemic disease within 4 weeks of cystoscopy will be completed.
The proportion of patients reporting a CR is reported here with confidence intervals for the true success proportion using the binomial distribution.
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Original Primary Outcome Measures ICMJE |
Complete response [ Time Frame: At 6 months from registration ] A two-stage study design will be utilized. Expression of immune signatures by RNA-sequencing (RNA-seq) expression (using the baseline tissue specimen) will be evaluated at baseline and explored in relation to clinical outcomes such as progression-free survival, tumor response, and adverse event incidence using two-way tables and box plots and analyzed using Fisher?s exact tests or logistic regression methods, as appropriate. Confidence intervals for the true success proportion will be calculated using the properties of the binomial distribution.
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Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Avelumab in Combination With Fluorouracil and Mitomycin or Cisplatin and Radiation Therapy in Treating Participants With Muscle-Invasive Bladder Cancer | ||||||
Official Title ICMJE | Phase II Study Evaluating Combination Chemotherapy + Radiotherapy (RT) With Avelumab in Muscle Invasive Bladder Cancer | ||||||
Brief Summary | This phase II trial studies the side effects of avelumab and how well it works in combination with fluorouracil and mitomycin or cisplatin and radiation therapy in treating participants with muscle-invasive bladder cancer. Monoclonal antibodies, such as avelumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as fluorouracil, mitomycin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving avelumab with chemotherapy and radiotherapy may work better in treating participants with muscle-invasive bladder cancer. | ||||||
Detailed Description |
PRIMARY OBJECTIVES: I. To evaluate the complete response rate of concurrent chemotherapy radiation treatment combined with avelumab for patients with muscle invasive bladder cancer. SECONDARY OBJECTIVES: I. To evaluate the safety and toxicity (adverse event profile) of concurrent chemotherapy radiation treatment combined with avelumab. II. To evaluate quality of life (QoL) at 1 year of concurrent chemotherapy radiation treatment combined with avelumab. III. To evaluate progression-free survival and relapse-free survival at 1 year with concurrent chemotherapy radiation treatment combined with avelumab. CORRELATIVE OBJECTIVES: I. To explore biomarkers that may predict response to avelumab in the muscle invasive population. II. To evaluate the association of tumor mutational burden with response to concurrent chemo- radiation and immunotherapy. III. To evaluate whether concurrent chemoradiation and immunotherapy after maximal transurethral resection of bladder tumor (TURBT) is associated with a decrease in circulating Bim+CD11a^high PD-1+CD8+ T-cells and myeloid-derived suppressor cells (MDSCs). OUTLINE: Participants receive avelumab intravenously (IV) over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants receive either fluorouracil IV on days 1-5 and 16-20 during radiation therapy (RT) and mitomycin IV on day 1 of course 3, or cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days, 6, 9, and 12 months. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (avelumab, chemotherapy, radiation therapy)
Participants receive avelumab IV over 60 minutes every 14 days for a total of 10 courses in the absence of disease progression or unacceptable toxicity. Beginning 29 days after the first dose of avelumab, participants receive either fluorouracil IV on days 1-5 and 16-20 during RT and mitomycin IV on day 1 of course 3, or cisplatin IV starting on day 1 of courses 3-5 for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE |
2 | ||||||
Original Estimated Enrollment ICMJE |
27 | ||||||
Actual Study Completion Date ICMJE | July 27, 2020 | ||||||
Actual Primary Completion Date | November 14, 2019 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03617913 | ||||||
Other Study ID Numbers ICMJE | MC1752 NCI-2018-01539 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MC1752 ( Other Identifier: Mayo Clinic in Arizona ) P30CA015083 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | Mayo Clinic | ||||||
Study Sponsor ICMJE | Mayo Clinic | ||||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||||
Investigators ICMJE |
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PRS Account | Mayo Clinic | ||||||
Verification Date | March 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |