Avelumab in Combination With Fluorouracil and Mitomycin or Cisplatin and Radiation Therapy in Treating Participants With Muscle-Invasive Bladder Cancer

NCT03617913 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MC1752NCI-2018-01539
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Complete Response (At 6 Months)

  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.

  At 6 months from registration

Secondary Outcomes (5)

• Adverse Events Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Up to 12 months

• Patient-reported Outcomes (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ]-30

  Baseline to 12 months

• Patient-reported Outcomes (European Organization for Research and Treatment of Cancer [EORTC] EORTCQOL-Muscle-Invasive Bladder Cancer Module [BLM]30

  Baseline to 12 months

• Progression-free Survival

  From registration to time of first documentation of progression or death from any cause, assessed up to 12 months

• Recurrence-free Survival

  From documented complete response to the first documentation of recurrence, assessed up to 12 months

Other Outcomes (3)

• Relationship of PD-L1 (SP263 and SP142), CD8+ by Immunohistochemistry

  Up to 12 months

• Tumor Mutational Burden With Response to Concurrent Chemo- Radiation and Immunotherapy

  Up to 12 months

• Evaluate Whether Concurrent Chemoradiation and Immunotherapy After Maximal TURBT is Associated With a Decrease in Circulating Bim+CD11ahighPD-1+CD8+ T-cells and MDSCs.

  Up to 12 months

Study Arms (1)

Treatment (avelumab, chemotherapy, radiation therapy)

EXPERIMENTAL

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.

Drug: Avelumab; Drug: Cisplatin; Drug: Fluorouracil; Drug: Mitomycin; Other: Quality-of-Life Assessment; Radiation: Radiation Therapy

Interventions

Avelumab DRUG

Given IV

Also known as: Bavencio, MSB-0010718C, MSB0010718C

Treatment (avelumab, chemotherapy, radiation therapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (avelumab, chemotherapy, radiation therapy)

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (avelumab, chemotherapy, radiation therapy)

Mitomycin DRUG

Given IV

Also known as: Ametycine, MITO, MITO-C, Mito-Medac, Mitocin, Mitocin-C, Mitolem, Mitomycin C, Mitomycin-C, Mitomycin-X, Mitomycine C, Mitosol, Mitozytrex, Mutamycin, Mutamycine, NCI-C04706

Treatment (avelumab, chemotherapy, radiation therapy)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (avelumab, chemotherapy, radiation therapy)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Treatment (avelumab, chemotherapy, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic proof of T2-T4a N0M0 (American Joint Committee on Cancer \[AJCC\] 8th edition) with predominant urothelial carcinoma. Mixed histologies are acceptable provided urothelial carcinoma is the predominant histology. Small cell urothelial carcinoma is excluded.
• Cystoscopy with maximal TURBT performed =\< 70 days of study registration. NOTE: Both completely resectable or partially resectable tumors are eligible as long as the treating urologist attempted complete resection. Exam under anesthesia needs to be performed and documented.
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 =\< 28 days prior to registration.
• Platelets (PLT) 100,000/mm\^3 =\< 28 days prior to registration.
• Total bilirubin =\< 1.5 upper limit of normal (ULN) =\< 28 days prior to registration.
• Aspartate transaminase (AST) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement) =\< 28 days prior to registration.
• Alanine aminotransferase (ALT) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement) =\< 28 days prior to registration.
• Hemoglobin (Hgb) \>= 9 gm/dl =\< 28 days prior to registration.
• Calculated creatinine clearance must be \>= 30 ml/min using the Cockcroft-Gault formula =\< 28 days prior to registration.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS 0, 1, 2).
• Ability to provide informed written consent.
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).
• Life expectancy \>= 6 months.
• Negative serum pregnancy test done =\< 14 days prior to registration, for women of childbearing potential only.

You may not qualify if:

• 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:
• Abdomen/pelvis computed tomography (CT) or magnetic resonance imaging (MRI) scan
• Chest x-ray or CT scan.
• Patients with concurrent urothelial carcinoma and/or related variants anywhere outside bladder
• NOTE: Patients with history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible.
• 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:
• Non-melanoma skin cancer and/or localized prostate cancer (T2 a or b , Gleason \< 3+4) or carcinoma in situ of the uterine cervix which has been adequately treated =\< 2 years prior to registration
• Or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai stage 0, prostate cancer with Gleason score =\< 3+4, and prostate-specific antigen \[PSA\] =\< 10 mg/mL, etc.).
• 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.
• EXCEPTION: Except single dose intravesical chemotherapy administered after TURBT.
• Patients who have received prior therapy with immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-LAG3, anti-CTLA-4, anti-TIM3) or immune co-stimulatory molecules (e.g. anti-CD137, anti-OX40, anti-GITR) directed agents.
• 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.
• NOTE: Patients who have had minor procedures (i.e. TURBT) or percutaneous biopsies prior to registration are eligible.
• Patients with history of cirrhosis, alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis.
• Patient with history of prior solid organ or allogeneic bone marrow transplant.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85054, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms; Urethral Neoplasms

Interventions

avelumab; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Fluorouracil; dehydroftorafur; Mitomycin; Mitozytrex; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Urethral Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Parminder Singh, MD
• Organization: Mayo Clinic

Singh.Parminder@mayo.edu

5072555123

Study Officials

• Parminder Singh

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: August 7, 2018
• Study Start: September 19, 2018
• Primary Completion: November 14, 2019
• Study Completion: July 27, 2020
• Last Updated: January 6, 2023
• Results First Posted: February 21, 2021

Record last verified: 2021-03

Locations

US (3)