Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer
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|ClinicalTrials.gov Identifier: NCT03300843|
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : August 3, 2018
Exomes are the parts of DNA that make proteins. Researchers are finding a way to read the letters in the exome. Incorrect letters are called mutations. Tumors contain specific mutations. Researchers can find these mutations in tumors to make treatments. Researchers want to use pieces of participants tumors to find the tumor-specific mutations. They also will take participants white blood cells to make a vaccine that they hope will shrink the tumors.
To see if dendritic vaccine tumor-fighting cells are safe and can cause certain cancer tumors to shrink.
Adults ages 18-70 who have metastatic melanoma or metastatic epithelial cancer
The first part of this study was done under protocol 03-C-0277. In that study, white blood cells and pieces of participants' tumors were taken to make a vaccine.
In this study, participants will get a vaccine every 2 weeks for 8 weeks. It will be given both in a vein and under the skin. At each visit, participants will have a physical exam and have blood taken. They will talk about any side effects they have.
After treatment ends, participants will have many follow-up visits for the first year, then once each year after that. Visits will last up to 2 days each. They will include lab tests, imaging studies, and a physical exam. Blood will be taken at each visit. At the first follow-up visit, participants may have leukapheresis, which they also had as part of protocol 03-C-0277. Participants may not have to return to the Clinical Center for these visits.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Gastrointestinal Cancer Breast Cancer Ovarian Cancer Pancreatic Cancer||Biological: Peptide loaded dendritic cell vaccine||Phase 2|
- Therapeutic vaccination against cancer has proven very challenging with little clinical benefit.
- Vaccines against non-viral tumors have mainly targeted differentiation antigens, cancer testis antigens, and overexpressed antigens. However negative selection in the thymus against these normal nonmutated antigens severely limits the ability to generate high avidity anti-cancer T cells. Such depletion can impair their antitumor activity and limit tumor elimination.
- The National Cancer Institute Surgery Branch (NCI SB ) has developed a pipeline for the identification of immunogenic T cell epitopes derived from neoantigens.
- In recent studies, we identified the neoantigens recognized by TIL that mediated regression in patients with metastatic cancer. Using whole exome sequencing of a resected metastatic nodule followed by high throughput immunologic screening, we were able to demonstrate that tumor regressions were associated with the recognition by the administered TIL of unique somatic mutations that occurred in the cancer.
- We, therefore, aim to use this pipeline to identify immunogenic neoantigens from epithelial cancer patients and to use these defined epitopes for a personalized therapeutic dendritic cell (DC) vaccine.
--To determine the clinical response rate in patients with metastatic melanoma or epithelial cancer who receive this DC vaccine
- Age greater than or equal to 18 and less than or equal to 70 years
- ECOG 0 - 2
- Evaluable metastatic melanoma or epithelial cancer refractory to standard treatment
- Metastatic melanoma or epithelial cancer lesion(s) that is resectable for TIL or in selected cases, available PBMC.
- Patients with metastatic melanoma or epithelial cancer will undergo surgical resection of tumor followed by exome and RNA sequencing to identify expressed mutations (CONDUCTED UNDER THE nci sb COMPANION PROTOCOL 03-c-0277).
- Patients will undergo apheresis and DC will be cryopreserved for vaccine preparation.
- Immunogenic neoantigens will be identified from TIL and PBMC by high throughput immunologic screening using long peptides and tandem minigenes covering all mutated epitopes.
- Patient will be vaccinated with autologous mature dendritic cells loaded with long peptides and minimal epitopes from defined neoantigens or highly expressed mutations in tumor suppressor or driver genes.
- DC will be administered intravenously and subcutaneously for four cycles at biweekly intervals.
- Blood samples will be taken every two weeks, and patients will be monitored for the quantity and quality of circulating neoantigen-specific T cells.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||86 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial to Evaluate the Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer|
|Actual Study Start Date :||April 11, 2018|
|Estimated Primary Completion Date :||February 2, 2027|
|Estimated Study Completion Date :||February 2, 2028|
Experimental: Experimental Therapy
Peptide loaded dendritic cell vaccine on days 0, 14, 28, and 42
Biological: Peptide loaded dendritic cell vaccine
On days 0, 14 (+/- 5 days), 28 (+/- 5 days), and 42 (+/- 5 days). The vaccine will be administered as both an intravenous (IV) infusion and a subcutaneous (SQ) injection. The total dose will be divided equally between IV and SQ containing 1.0E7 to 8.0E7 cells per cycle depending upon the manufacturing yield.
- Response rate [ Time Frame: 2 weeks after 4th vaccine, then 1 month x1, then every 2 months for the 1st year, then as annually. ]Percentage of patients who have a clinical response to treatment
- Quantity and quality of circulating antigen-specific T cells [ Time Frame: approximately 6 years after cell infusion ]Eliza and Elispot assays assessing reactivity to the mutated peptidecompared to the non-mutated peptide
- Frequency of treatment related adverse [ Time Frame: 30 days after the first follow-up evaluation on Day 56 ]Aggregate of all adverse events and their frequency
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): NCT03300843
|Contact: Margaret Shovlin, R.N.||(866) 820-4505||IRC@nih.gov|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center 866-820-4505 firstname.lastname@example.org|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|