Dendritic Cell Therapy After Cryosurgery in Combination With Pembrolizumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Remove by Surgery
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03325101|
Recruitment Status : Active, not recruiting
First Posted : October 30, 2017
Last Update Posted : December 2, 2021
|Condition or disease||Intervention/treatment||Phase|
|Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7||Procedure: Cryosurgery Biological: Pembrolizumab Procedure: Pheresis Biological: Therapeutic Autologous Dendritic Cells||Phase 1 Phase 2|
I. To determine the objective response rate (ORR) of pembrolizumab combined with cryoablation and intratumoral mature dendritic cells (mDCs) in patients with metastatic melanoma that has failed to respond or has stopped responding to initial therapy with a PD-1 axis-blocking monoclonal antibody.
I. To assess the safety profile of pembrolizumab combined with cryoablation and intratumoral mDCs in patients with metastatic melanoma that have failed to respond or have stopped responding to initial therapy with a PD-1 axis-blocking monoclonal antibody.
II. To determine median progression-free survival (PFS) obtained with this approach in this patient population.
III. To determine median overall survival (OS) obtained with this approach in this patient population.
I. To quantitate tumor infiltrating lymphocytes (TILs) in tumor biopsies prior to and following cryoablation and intratumoral mDCs.
II. To measure PD-L1 levels in tumor biopsies and blood biopsies prior to and following cryoablation and to assess whether a change in PD-L1 levels differ among those patients who met the criteria for clinical benefit (progression-free and on study for at least 6 months) and those who do not.
III. To measure peripheral blood mononuclear cells (PBMC) proliferation and function after coculture with frozen tumor before and after intratumoral mDC injection.
Patients undergo apheresis over 4 hours on day 1 or course 1. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses with pembrolizumab repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 36 hours after receiving pembrolizumab, patients undergo cryosurgery over 45 minutes on day 1 or 2 of courses 2 and 3. Patients also receive mature dendritic cells intratumorally (IT) on day 1 or 2 of courses 2 and 3 after cryosurgery.
After completion of study treatment, patients are followed for up to 5 years
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Study of Autologous Dendritic Cell Therapy Delivered Intratumorally After Cryoablation in Combination With Pembrolizumab for Patients With Metastatic or Unresectable Melanoma|
|Actual Study Start Date :||November 15, 2017|
|Actual Primary Completion Date :||July 21, 2021|
|Estimated Study Completion Date :||October 31, 2022|
Experimental: Treatment (apheresis, pembrolizumab, cryosurgery, mDCs)
Patients undergo apheresis over 4 hours on day 1 or course 1. Patients also receive pembrolizumab IV over 30 minutes on day 1. Courses with pembrolizumab repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Within 36 hours after receiving pembrolizumab, patients undergo cryosurgery over 45 minutes on day 1 or 2 of courses 2 and 3. Patients also receive mature dendritic cells IT on day 1 or 2 of courses 2 and 3 after cryosurgery.
Biological: Therapeutic Autologous Dendritic Cells
- Tumor response rate [ Time Frame: Up to 5 years ]Will be defined as the number of patients whose disease meets the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for a partial (PR) or complete (CR) on two consecutive evaluations at least 4 courses (approximately 84 days) apart divided by the total number of patients who started protocol treatment at the continuation dose level. A 90% exact binomial confidence interval for the tumor response rate will be constructed.
- Clinical benefit rate defined as the proportion of patients who have completed 6 courses of treatment without disease progression [ Time Frame: Up to 5 years ]A 90% exact binomial confidence interval for this proportion will be constructed.
- Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 5 years ]Toxicities will be graded in terms of severity and relationship to study treatment using CTCAE criteria. For each patient who initiated treatment, the maximum grade of each toxicity noted during treatment will be recorded. Frequency tables will be constructed by treatment schedule.
- Overall survival [ Time Frame: From registration to death due to any cause assessed up to 5 years ]The distribution of overall survival times will be estimated using the Kaplan-Meier approach.
- Progression-free survival [ Time Frame: From randomization to the first 2 consecutive evaluations approximately 6 weeks apart assessed up to 5 years ]The distribution of progression free survival times will be estimated using the Kaplan-Meier approach.
- Proportion of patients who received both intratumoral dendritic cell injections among those who initiated treatment [ Time Frame: Up to 5 years ]Will be determined. A 95% exact binomial confidence interval for this proportion will be constructed.
- Change in PD-L1 levels [ Time Frame: Baseline up to 6 months progression-free survival ]Will be assessed using the Wilcoxon rank sum tests.
- Change in the number of tumor infiltrating lymphocytes (TILs) in tumor biopsies [ Time Frame: Baseline up to 6 months progression-free survival ]The percent change in the number of TILs following cryosurgery and intratumoral mature dendritic cells (mDCs) from pre- cryosurgery and intra-tumoral mDCs levels will be determined.
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): NCT03325101
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Matthew Block||Mayo Clinic|