Phase 2 Study of Pembrolizumab in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy
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|ClinicalTrials.gov Identifier: NCT02690558|
Recruitment Status : Active, not recruiting
First Posted : February 24, 2016
Results First Posted : August 10, 2021
Last Update Posted : October 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: pembrolizumab, gemcitabine and cisplatin||Phase 2|
Primary Objective To estimate the proportion of patients with pathological downstaging to <pT2 after neoadjuvant therapy with pembrolizumab in combination with gemcitabine and cisplatin in patients with MIBC
Hypothesis: The rate of pathologic downstaging to <pT2 will improve compared to historical controls
Secondary Objectives To estimate the proportion of patients with pT0 after neoadjuvant therapy with pembrolizumab when administered in combination with gemcitabine and cisplatin in patients with MIBC
Hypothesis: The rate of pathologic downstaging to pT0 will improve compared to historical controls
To estimate event free survival (EFS) Hypothesis: EFS will be improved compared to historical controls
To estimate overall survival (OS) Hypothesis: OS will be improved compared to historical controls
To estimate the proportion of patients who are alive at 3 years (OS at 3 years) Hypothesis: OS at 3 years will be improved compared to historical controls
To characterize the toxicity profile for the combination of pembrolizumab, gemcitabine, and cisplatin Hypothesis: Pembrolizumab, gemcitabine, and cisplatin will be a safe combination with acceptable toxicity rates
Exploratory Objectives To explore the association of biological markers including PD-L1 expression and immune gene expression signatures with pathological downstaging to <pT2, pT0, EFS, and OS
To explore associations between BASE47 "basal," "claudin-low," and "luminal" subtypes of MIBC and pathological downstaging to <pT2, pT0, EFS, and OS
To characterize the change in phenotype of TILs, including delineation of effector and regulatory T cells, before and after neoadjuvant treatment
To define T cell receptor (TCR) and B cell receptor (BCR) repertoire profiles that are associated with pathological downstaging to <pT2, pT0, EFS, and OS
First the participant will receive all 3 study drugs (Pembrolizumab/Keytruda, gemcitabine and cisplatin) on the first day of a 3 week "cycle". The participant will then receive cisplatin and gemcitabine on the 8th day of the cycle.
The participant will receive the study drugs for 4 cycles for a total of 12 weeks.
Participants are followed for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Masking Description:||open label|
|Official Title:||Phase II Single Arm Study of Gemcitabine and Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer|
|Actual Study Start Date :||May 2016|
|Actual Primary Completion Date :||July 6, 2020|
|Estimated Study Completion Date :||January 30, 2026|
Experimental: pembrolizumab, gemcitabine and cisplatin
There is one arm in this study. Subjects will receive Pembrolizumab 200mg IV on day 1 in combination with cisplatin 35mg/m2 and gemcitabine 1000mg/m2 on day 1 and day 8 every 3 weeks for 4 cycles over 12 weeks.
Drug: pembrolizumab, gemcitabine and cisplatin
neoadjuvant administration of pembrolizumab with gemcitabine and cisplatin prior to cystectomy
- Percentage of Subjects That Reach Pathological Downstaging (Response) at the Time of Cystectomy [ Time Frame: 14 weeks of treatment plus cystectomy within 70 days after treatment ]
Pathologic (p) anatomic stage for bladder cancer uses the American Joint Committee on Cancer (AJCC) Tumor/Nodes/Metastasis (TNM) system, which is based on:
Size of primary tumor (T) and whether it has grown into nearby areas. Spread to regional lymph nodes (N). Spread (metastasis; M) to other organs of the body. Once the T, N, and M categories have been determined, this information is combined into a prognostic group. Higher numbers mean the cancer is more advanced.
Pathologic staging is based on the operative and pathology report from cystectomy at the local site. A pathologic response or downstaging is defined as a reduction in stage to below pathological tumor stage 2 (<pT2) (pT0-T1N0M0)
- Percentage of Subjects That Reach Complete Pathologic Response (pT0) at the Time of Cystectomy [ Time Frame: 14 weeks of treatment plus cystectomy within 70 days of treatment ]
Pathologic (p) anatomic response for bladder cancer uses the American Joint Committee on Cancer (AJCC) TNM staging system, which is based on:
Size of primary tumor (T) and whether it has grown into nearby areas. Spread to regional lymph nodes (N). Spread (metastasis) (M) to other organs of the body. Once the T, N, and M categories have been determined, this information is combined into a prognostic group. Higher numbers mean the cancer is more advanced.
Pathologic staging is based on the operative and pathology report from cystectomy at the local site.
Complete pathologic response (pT0) is defined as pT0 N0 M0.
- Event Free Survival [ Time Frame: 14 weeks of treatment plus 5 years of followup ]defined from D1 of neoadjuvant treatment until progression (in those who progress prior to surgery) or until recurrence (post-surgery) or until death as a result of any cause.
- Overall Survival (OS) [ Time Frame: 14 weeks of treatment plus 3 years or until death ]OS at 3 years is defined from D1 of treatment until 3 years or death as a result of any cause
- Number of Participants With Treatment Related Adverse Events. [ Time Frame: 14 weeks of treatment plus 30 days for toxicity followup ]Safety and toxicity will be characterized according to the reported adverse event (AE) profile using NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0, a descriptive terminology. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02690558
|United States, North Carolina|
|North Carolina Cancer Hospital (UNC)|
|Chapel Hill, North Carolina, United States, 27599|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Matthew I Milowsky, MD||UNC Lineberger Comprehensive Cancer Center|