Pembrolizumab and Combination Chemotherapy Before Surgery for the Treatment of Muscle-Invasive Bladder Cancer

NCT04383743 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1006206NCI-2019-0802810439
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study is evaluating how well pembrolizumab and combination chemotherapy before surgery work for the treatment of specific types of muscle-invasive bladder cancer that have unusual appearance (variants). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, vinblastine, adriamycin, 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. Giving pembrolizumab and combination chemotherapy before surgery may work better in treating patients with these muscle invasive bladder cancer variants compared to chemotherapy alone.

Conditions

Stage II Bladder Cancer AJCC v8; Stage IIIA Bladder Cancer AJCC v8; Muscle Invasive Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate

  Percentage of patients with no histologic evidence of tumor at time of cystectomy (ypT0N0)

  At time of radical cystectomy at approximately within 10 weeks of last neoadjuvant infusion

Secondary Outcomes (4)

• Frequency of Any Adverse Event According to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) Related to Study Therapy.

  Up to 90 days post study therapy completion

• Frequency of Grade 3 or Greater Adverse Events According to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) Related to Study Therapy.

  Up to 90 days post therapy completion

• Estimated 2-year Event-free Survival (EFS)

  At 2 years

• Number of Participants Able to Undergo Radical Cystectomy Within 10 Weeks From Completion of Study Therapy

  within 10 weeks from completion of study therapy

Other Outcomes (1)

• Tumor Infiltrating Lymphocyte (TIL) Density

  At time of Transurethral Bladder Tumor Resection and radical cystectomy

Study Arms (1)

Treatment (pembrolizumab, aMVAC)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 of weeks 0, 3, and 6 and methotrexate IV, vinblastine IV, doxorubicin IV, and cisplatin IV on day 1 of weeks 0, 2, 4, and 6 in the absence of disease progression or unacceptable toxicity. Patients also receive pegfilgrastim SC on day 1 or 2 of weeks 0, 2, 4, and 6 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care radical cystectomy.

Drug: Cisplatin; Drug: Doxorubicin; Drug: Methotrexate; Biological: Pegfilgrastim; Biological: Pembrolizumab; Procedure: Radical Cystectomy; Drug: Vinblastine Sulfate

Interventions

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 (pembrolizumab, aMVAC)

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Treatment (pembrolizumab, aMVAC)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Treatment (pembrolizumab, aMVAC)

Pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Neulastim, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim-jmdb, SD-01, SD-01 sustained duration G-CSF, Nyvepria, Pegcyte, Udenyca, Ziextenzo

Treatment (pembrolizumab, aMVAC)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, aMVAC)

Radical Cystectomy PROCEDURE

Undergo standard of care radical cystectomy

Also known as: Complete Cystectomy

Treatment (pembrolizumab, aMVAC)

Vinblastine Sulfate DRUG

Given IV

Also known as: 29060 LE, 29060-LE, Exal, Velban, Velbe, Velsar, VINCALEUKOBLASTINE

Treatment (pembrolizumab, aMVAC)

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed diagnosis of muscle invasive bladder cancer (cT2-T4a, N0-N1, M0 clinical stage per American Joint Commission on Cancer \[AJCC\]). Clinical node-positive (N1) patients are eligible provided the lymph nodes (LNs) are confined to the true pelvis and are within the planned surgical LN dissection template
• Histology must be either pure or predominant non-urothelial histology (noted on any TURBT)
• Participants must be deemed eligible for cisplatin-based chemotherapy, radical cystectomy (RC) and pelvic lymph node dissection (PLND) by urologist and medical oncologist
• Patients must agree to undergo curative intent surgery
• TURBT that showed muscularis propria invasion should be within 12 weeks prior to beginning study therapy. Patients must have available tumor tissue from either initial or repeat TURBT, prior to starting study therapy. Archival tumor tissue sample of a tumor lesion (TURBT specimen) should be provided and must contain muscle invasive component, at least \>= T2 tumor. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory, preferably within 14 days from the date slides are cut if possible. Patient must be willing to provide tumor tissue for research. Research samples will not be used for any studies unrelated to this trial
• Must have clinical non-metastatic bladder cancer (M0) determined by cross-sectional computed tomography (CT) chest, abdomen and pelvis (CAP) or magnetic resonance imaging (MRI) imaging
• A male participant must agree to use a contraception during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Evaluation is to be performed within 7 days prior to the date of enrollment
• Absolute neutrophil count (ANC) \>= 1500/uL (collected within 10 days prior to the start of study treatment)
• Platelets \>= 100 000/uL (collected within 10 days prior to the start of study treatment)
• Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (collected within 10 days prior to the start of study treatment)

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Patients with pure small cell histology will be excluded. Mixed histology including partial neuroendocrine small cell features will be permitted
• Patients considered to be medically unfit for accelerated (dose dense) MVAC chemotherapy, TURBT or RC (per investigator discretion) will be excluded
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks. Intravesical therapies are allowed without specified treatment interval
• Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =\< grade 1 or baseline. If participant had major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and should not have active radiation pneumonitis
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, a version of varicella/zoster (chicken pox), yellow fever, rabies, Bacillus calmette-guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing \> 10 mg daily of prednisone dose equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Has known additional malignancy that is progressing or has required active systemic treatment within the past 2 years. Note: Participants with basal cell carcinoma or squamous cell carcinoma of the skin, or any carcinoma in situ that have undergone potentially curative therapy are not excluded. Low/intermediate risk prostate cancer with prior potentially curative therapy, or no intent of future systemic therapy and/or radiation is allowed. Non-invasive (Tis, Ta) upper urinary tract (renal pelvis/ureter) is allowed. Urethra cancer with prior curative intent therapy with no active recurrence is also allowed regardless of time elapsed
• Has known locally advanced (unresectable) or metastatic cancer on baseline radiographic imaging (CT or MRI) obtained within 28 days prior to study registration
• Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Note: Patients with active well controlled type 1 diabetes mellitus, vitiligo, Graves' disease, Hashimoto disease, eczema, lichen simplex chronicus, or psoriasis, not requiring systemic immunosuppression within the past 2 years are not excluded

Sponsors & Collaborators

• University of Washington: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Doxorubicin; Methotrexate; merphos; pegfilgrastim; pembrolizumab; Cystectomy; Vinblastine

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Petros Grivas
• Organization: University of Washington

pgrivas@uw.edu

2066061943

Study Officials

• Petros Grivas

  Fred Hutch/University of Washington Cancer Consortium

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 12, 2020
• Study Start: November 24, 2020
• Primary Completion: June 17, 2024
• Study Completion: March 4, 2025
• Last Updated: September 18, 2025
• Results First Posted: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)