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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03319745
Other study ID # 2017-0057
Secondary ID NCI-2018-0103220
Status Completed
Phase Phase 2
First received
Last updated
Start date January 11, 2018
Est. completion date May 1, 2023

Study information

Verified date November 2023
Source M.D. Anderson Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase II trial studies the side effects of pembrolizumab and to see how well it works in treating patients with bladder cancer who are undergoing surgery to remove the bladder. 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.


Description:

PRIMARY OBJECTIVE: I. To characterize the safety profile of pembrolizumab in patients with urothelial carcinoma undergoing radical cystectomy. SECONDARY OBJECTIVES: I. To explore a signal of anti-cancer immunological activity by evaluating surgical specimens for evidence of post-treatment lymphocytic infiltration and residual tumor compared to pre-treatment biopsy samples. II. To explore a signal of biomarker activity by evaluating surgical specimens and blood samples for established and not-so-established markers of response to pembrolizumab. III. To report the tumor yield and sufficiency of tumor for immunological and biomarker activity. IV. To examine the interaction of the human microbiome and pathologic response to pembrolizumab. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. About 4 weeks after treatment, patients then undergo radical cystectomy per standard of care. After completion of study treatment, patients are followed up to 30 and 90 days.


Recruitment information / eligibility

Status Completed
Enrollment 23
Est. completion date May 1, 2023
Est. primary completion date May 1, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Be willing and able to provide written informed consent. - Have absence of metastatic disease as determined by conventional imaging studies and be considered a good surgical candidate by the treating physician. - Be willing to participate in the collection of blood and tissue for banking and future correlative studies. - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale. - Absolute neutrophil count (ANC) >= 1,500 /mcL. - Platelets >= 100,000/mcL. - Hemoglobin (Hgb) >= 9 g/dL or >= 5.6 mmol/L without (w/o) transfusion within 7 days of assessment. - Creatinine OR calculated creatinine clearance =< 1.5 x upper limit of normal (ULN) OR >= 30 mL/min for subject with creatinine levels > 1.5 x institutional ULN. Creatinine clearance should be calculated per institutional standard. - Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x ULN - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases. - Albumin > 2.5 mg/dL. - Coagulation international normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. - Female subject of childbearing potential should have a negative urine or serum pregnancy 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. - Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. - Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Exclusion Criteria: - Is currently participating and receiving pembrolizumab or has participated in a study of an investigational agent and received pembrolizumab or used an investigational device within 4 weeks of the first dose of study 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 study treatment. - Has a known history of active TB (Bacillus tuberculosis). - Has a known history of hypersensitivity to pembrolizumab or any of its excipients. - Has had prior systemic anti-cancer therapy for the treatment of bladder cancer. Prior intravesical therapies, whether Bacillus Calmette-Guerin (BCG) (including but not limited to: persistent high-grade disease or recurrence within 6 months of receiving at least two courses of intravesical BCG [at least five of six induction doses and at least two of three maintenance doses]; or T1 high-grade disease at the first evaluation following induction BCG alone [at least five of six induction doses]), chemotherapy or otherwise, will remain eligible. - Has any other malignancy diagnosed within 2 years of screening with the exception of basal or squamous cell skin cancer, or non-invasive cancer of the cervix, or any other cancer deemed by the treating physician to be of low-risk for progression or patient morbidity during the study period. - Has known metastatic disease as determined by conventional staging studies. - 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. - Has known history of, or any evidence of active, non-infectious pneumonitis. - Has a clinically significant active 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 physician. - 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 120 days after the last dose of trial treatment. - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. - Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). - Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected). - Has received a live vaccine within 30 days of initiation of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Pembrolizumab
Given IV

Locations

Country Name City State
United States M D Anderson Cancer Center Houston Texas

Sponsors (2)

Lead Sponsor Collaborator
M.D. Anderson Cancer Center National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 Toxicity of concern (TOX) will be monitored using the methods of Thall et al. TOX events will be reported with a 95% credible interval assuming a non-informative prior of beta. Specific events will also be summarized. All adverse events and surgical complications will be reported overall by grade, attribution, and treatment period. Up to 30 days post-surgery
Secondary Biomarker activity of Pembrolizumab in Patients with Bladder Cancer Undergoing Radical Cystectomy Tissue evaluated for signals of biomarker activity by evaluating surgical specimens for established and not-so-established markers of response to pembrolizumab (e.g. TILS, PD-1 and PD-L1 levels) compared to pre-treatment biopsy samples. Baseline up to 90 days after surgery
See also
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Recruiting NCT04953104 - Nivolumab for the Treatment of Patients With Metastatic Urothelial Cancer With ARID1A Mutation and Stratify Response Based on CXCL13 Expression Phase 2
Completed NCT03617913 - Avelumab in Combination With Fluorouracil and Mitomycin or Cisplatin and Radiation Therapy in Treating Participants With Muscle-Invasive Bladder Cancer Phase 2
Withdrawn NCT05564416 - Testing Anti-Cancer Drugs Erdafitinib With or Without Atezolizumab in Patients With Localized Bladder Cancer Not Able to Receive Cisplatin Chemotherapy, NERA Trial Phase 2
Recruiting NCT03375307 - Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes Phase 2
Active, not recruiting NCT03854474 - Testing the Addition of Tazemetostat to the Immunotherapy Drug, Pembrolizumab (MK-3475), in Advanced Urothelial Carcinoma Phase 1/Phase 2
Active, not recruiting NCT04216290 - A Study of Chemotherapy and Radiation Therapy Compared to Chemotherapy and Radiation Therapy Plus MEDI4736 (Durvalumab) Immunotherapy for Bladder Cancer Which Has Spread to the Lymph Nodes (The INSPIRE Study) Phase 2
Active, not recruiting NCT03513952 - Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma Phase 2
Active, not recruiting NCT05092958 - Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study Phase 3
Active, not recruiting NCT02496208 - Cabozantinib S-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors Phase 1
Active, not recruiting NCT03237780 - Atezolizumab With or Without Eribulin Mesylate in Treating Patients With Recurrent Locally Advanced or Metastatic Urothelial Cancer Phase 2
Recruiting NCT06414317 - An Education and Navigation Support Tool to Improve Participation in Care Coordination Among Patients With Locally Advanced, Metastatic and Unresectable Bladder Cancer and Their Caregivers N/A
Active, not recruiting NCT04501913 - Remote Telemonitoring of Patient-Generated Physiologic Health Data and Patient-Reported Outcomes
Completed NCT03582475 - Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate Phase 1
Recruiting NCT04902040 - Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies Phase 1/Phase 2

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