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2016-05-11
2027-05-31
2027-05-31
150
NCT02600949
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
INTERVENTIONAL
Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer
This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Personalized peptide vaccine is a vaccine developed from patient's own tumor cells and blood in order to use as a biological therapy. Biological therapies, such as personalized peptide vaccine may attack tumor cells and stop them from growing or kill them.
PRIMARY OBJECTIVES: I. Demonstrate that developing a custom vaccine for metastatic pancreatic ductal adenocarcinoma (PDA) and colorectal cancer (CRC) patients is feasible. (cohorts A and B) II. Show that a custom peptide-based vaccine in combination with imiquiomod, pembrolizumab, and/or sotigalimab (APX005M) is safe. (cohorts A and B and C and D) SECONDARY OBJECTIVES: I. Determine the clinical benefit of the peptide vaccine alone or combined with pembrolizumab or pembrolizumab and APX005M. (cohorts A and B and C and D) II. Demonstrate the antigenicity of each vaccine. (cohorts A and B and C and D) III. The change in neoantigen-specific T cell responses at 12 weeks after initiation of personalized peptide vaccination. (cohorts C and D) IV. Relapse-free survival and circulating tumor deoxyribonucleic acid (ctDNA) clearance rate. (cohorts C and D) OUTLINE: Patients are assigned to 1 of 3 cohorts. COHORT A: Patients receive personalized synthetic tumor-associated peptide vaccine therapy subcutaneously (SC) on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39. COHORT B: Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab intravenously (IV) over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39. COHORTS C AND D: Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39. After completion of study treatment, patients are followed for 6 months.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2015-11-06 | N/A | 2025-08-11 |
2015-11-06 | N/A | 2025-08-13 |
2015-11-09 | N/A | 2025-08 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Non Randomized
Interventional Model:
Parallel
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Cohort A (personalized vaccine, imiquimod) Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of dis | DRUG: Imiquimod
BIOLOGICAL: Synthetic Tumor-Associated Peptide Vaccine Therapy
PROCEDURE: Computed Tomography
PROCEDURE: Magnetic Resonance Imaging
|
| EXPERIMENTAL: Cohort B (personalized vaccine, imiquimod, pembrolizumab) Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pem | DRUG: Imiquimod
BIOLOGICAL: Pembrolizumab
BIOLOGICAL: Synthetic Tumor-Associated Peptide Vaccine Therapy
PROCEDURE: Computed Tomography
PROCEDURE: Magnetic Resonance Imaging
|
| EXPERIMENTAL: Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M) Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients a | DRUG: Imiquimod
BIOLOGICAL: Pembrolizumab
BIOLOGICAL: Sotigalimab
BIOLOGICAL: Synthetic Tumor-Associated Peptide Vaccine Therapy
PROCEDURE: Computed Tomography
PROCEDURE: Magnetic Resonance Imaging
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Proportion of enrolled patients for whom a personalized vaccine is developed and ready to administer (cohorts A and B) | Up to 12 weeks post-enrollment | |
| Proportion of enrolled patients who receive at least 1 dose of vaccine at any time post-enrollment (cohorts A and B) | Up to 44 weeks | |
| Incidence of adverse events (AEs) | Defined as the proportion of subjects who experience at least one toxicity event per National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. A toxicity event is defined as at least one grade 3 or 4 non-hematologic or grade 4 hematologic toxicity. Proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval. | Up to 24 weeks |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Proportion of patients who have received at least one dose of vaccine that is alive and progression free defined based on response criteria according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Progression free includes complete response (CR), partial response (PR), and stable disease (SD). The target proportion is 45%, and a proportion of 20% or lower will be considered as not having the desired efficacy. | At 12 weeks post-vaccination (second re-staging scan) |
| Progression-free survival (cohorts A and B and C) | Estimated by the Kaplan-Meier method, along with the 95% confidence intervals, and log-rank test will be used to assess the time to event variable differences under different patient subgroups. | The time between the date of first vaccination and evidence of progression on computed tomography scan or the date of death due to any cause, assessed up to 6 months after the last dose of vaccine |
| Response rate (cohort A and B) | Response rate includes both CR and PR and will be evaluated using a Simon optimal two-stage design. | Up to 12 weeks |
| Change in tumor biomarker (CA19-9, carcinoembryonic antigen [CEA] or circulating free deoxyribonucleic acid [cfDNA] mutation) | Up to 6 months | |
| Overall survival | Estimated by the Kaplan-Meier method, along with the 95% confidence intervals, and log-rank test will be used to assess the time to event variable differences under different patient subgroups. | The time from first vaccination to death, assessed up to 6 months after the last dose of vaccine |
| Recurrence-free survival (cohort C and D) | Estimated by the Kaplan-Meier method. | Up to 6 months |
| Rate of circulating deoxyribonucleic acid (ctDNA) clearance (cohort C and D) | A linear mixed model will also be fitted to correlate ctDNA clearance and neoantigen-specific CD8+ T cell over time. | Up to 6 months |
| Change in neoantigen-specific T cell response (cohort C and D) | The difference in log2 transformed T cell response from baseline to 12 weeks will be calculated for each peptide and patient. This endpoint will focus upon the log2-fold change at 12 weeks for the max peptide (i.e., the peptide with the greatest change). Descriptive statistics, including mean, standard deviation, median and range, will be used to summarize the changes. A paired t-test will be used to evaluate the changes from baseline to 12 weeks post initiation of vaccination. | Baseline to 12 weeks after initiation of personalized peptide vaccination |
| Correlation of T-cell activation against vaccinated peptides and ctDNA dynamics (cohort C and D) | Up to 6 months | |
| Tumor microenvironment immune infiltration and progression biopsies (cohort C and D) | Baseline, up to 6 months | |
| T cell IFN-gamma release in response to selected personalized peptide antigens | Up to 6 months | |
| Levels of intracellular cytokine staining of T cells | Assessed by flow cytometry in response to stimulation with personalized peptide antigens. | Up to 6 months |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
