Pembrolizumab in Treating Participants With Metastatic, Recurrent or Locally Advanced Cancer and Genomic Instability
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03428802|
Recruitment Status : Recruiting
First Posted : February 12, 2018
Last Update Posted : October 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|BRCA1 Gene Mutation BRCA2 Gene Mutation Locally Advanced Solid Neoplasm Metastatic Malignant Solid Neoplasm POLD1 Gene Mutation POLE Gene Mutation Recurrent Malignant Solid Neoplasm Recurrent Ovarian Carcinoma Stage III Breast Cancer AJCC v7 Stage III Ovarian Cancer AJCC v8 Stage IIIA Breast Cancer AJCC v7 Stage IIIA Ovarian Cancer AJCC v8 Stage IIIB Breast Cancer AJCC v7 Stage IIIB Ovarian Cancer AJCC v8 Stage IIIC Breast Cancer AJCC v7 Stage IIIC Ovarian Cancer AJCC v8 Stage IV Breast Cancer AJCC v6 and v7 Stage IV Ovarian Cancer AJCC v8 Stage IVA Ovarian Cancer AJCC v8 Stage IVB Ovarian Cancer AJCC v8||Other: Laboratory Biomarker Analysis Biological: Pembrolizumab||Phase 2|
I. To evaluate the response rate of pembrolizumab in participants with evidence of genomic instability who have solid tumors with POLE and POLD1 mutations.
II. To evaluate the response rate of pembrolizumab in participants with evidence of genomic instability who have solid tumors with BRCA1/2 mutations.
I. To compare the complete and partial response rate, and response durability (immune related progression free survival), to historical cohort information of unselected patients treated with pembrolizumab.
I. To evaluate the CD4+ and CD8+ T cell response in the tumor microenvironment and peripheral blood of patients treated on this study as well as the frequencies, activation/differentiation, functionality, and co-inhibitory molecule expression of immune cell populations in peripheral blood and tumor, before and after treatment with systemic pembrolizumab.
II. To measure PD-L1 expression in pretreatment tumor biopsies and in post treatment tumor tissue, as well as on biopsies taken at progression, to capture data on the relationship between PD-L1 expression and patient outcome.
III. To perform deep sequencing for detection of PD-1 and PD-L1 polymorphisms that may correlate with clinical outcomes as well as identification of mutations in immunoregulatory genes that are potential predictors of response to these therapies.
IV. To perform exome sequencing of pre-treatment tumor specimens to determine if the presence of immunogenic neoantigens is associated with response.
V. To perform ribonucleic acid (RNA) sequencing to determine if expression of checkpoint genes, immune-regulatory modules, or non-coding RNAs including repetitive RNAs and retroelements are associated with response.
Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants with disease progression may continue pembrolizumab for up to 1 year.
After completion of study treatment, participants are followed up at 30 days then every 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Basket Trial of Pembrolizumab in Patients With Advanced Solid Tumors and Genomic Instability|
|Actual Study Start Date :||March 8, 2018|
|Estimated Primary Completion Date :||October 2, 2020|
|Estimated Study Completion Date :||October 2, 2020|
Experimental: Treatment (pembrolizumab)
Participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants with disease progression may continue pembrolizumab for up to 1 year.
Other: Laboratory Biomarker Analysis
- Response rate of pembrolizuab [ Time Frame: Up to 2.5 years ]Will calculate the 95% confidence intervals (CI?s) to assess precision of expected response rate of pembrolizumab in treating patients with specified mutant tumors.
- Progression free survival [ Time Frame: 6 months ]Will calculate with 95% CI calculations.
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): NCT03428802
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Janice M. Mehnert 732-235-8945 firstname.lastname@example.org|
|Principal Investigator: Janice M. Mehnert|
|Principal Investigator:||Janice Mehnert||Rutgers Cancer Institute of New Jersey|