Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Recurrence

Brain Neoplasms

Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

All Drugs and Chemicals

Vaccines

Patients will receive the vaccine monthly (+/- 3 days) for 6 doses as a priming phase followed by booster injections quarterly Q3mo thereafter. If sufficient quantities of vaccine are available, vaccination may continue until development of intolerance or disease progression in the case of fatal high grade neoplasms or for up to one year. Additionally, patients with non-fatal tumors who complete one year of vaccinations and have stable disease at the completion of treatment will be given the option of resuming vaccinations if they develop subsequent progression.

At each vaccination time point, patients will receive one injection of the neoantigen DNA vaccine, one injection into the vastus lateralis.

Personalized neoantigen DNA vaccine

All study injections will be given intramuscularly using an integrated electroporation device (TDS-IM v2.0 device - Papivax Biotech).

Papivax Biotech TDS-IM v2.0

-After trial enrollment and up to 7 days after the first vaccine dose (baseline); no more than 2 weeks after the 3rd vaccine dose; no more than 2 weeks after the 6th vaccine dose; two weeks after the last dose; time of progression or discontinuation (optional)

Peripheral blood draw

Margaret S Shatara, M.D.

Mohamed Abdelbaiki, M.D.

Nicole Brossier, M.D., Ph.D.

William E Gillanders, M.D.

Robert Schreiber, Ph.D.

Maxim Artyomov, Ph.D.

David Spencer, M.D., Ph.D.

Jarod Roland, M.D.

Milan Chheda, M.D.

Brian Goetz

Jingquin (Rosy) Luo, Ph.D.

Andrew Cluster, M.D.

The purpose of this research study is to learn about the safety and feasibility of giving a personalized DNA vaccine to people with brain tumors that have returned or have been resistant to treatment.

Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors

A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors

* PFS is defined as the duration of time from date of first dose of vaccine to date of progression or evidence of last progression free time.
* Progressive Disease (PD): At least a 25% increase in the sum of products of perpendicular diameters of at least 1 target lesion, taking as reference the smallest sum of products of perpendicular diameters on study (this includes the baseline sum if that is the smallest on study). The absolute increase in any dimension must be at least 5mm when calculating the products of perpendicular diameters. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy\* not caused by comorbid events.

-OS is defined as date of first dose of vaccine to date of death or date of last known alive.

Children's Discovery Institute

Washington University School of Medicine

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

* Vaccines will be weeks 1, 5, 9, 13, 17, and 21. Vaccines will occur within +/- 1 week with at least 3 weeks between vaccines. All study injections will be given intramuscularly using TDS-IM system. At each vaccination time point, patients will receive 2 injections of the neoantigen DNA vaccine, 1 injection into each deltoid or lateralis.
* Minimum observation of 30 minutes. Vital signs will be taken at 30-45 minutes post-immunization. The injection sites will be inspected for evidence of local reaction. Follow up on subject well-being will be performed by telephone on the 1st or 2nd day following each injection. -Post-vaccination follow-up visits are at Week 25 ± 7 days and Week 77 ± 14 days. Additional follow-up visits or telephone contact will be scheduled at Week 129 and annually thereafter if the patient is alive and available for follow-up.
* At intervals throughout the study (both before and after vaccination) subjects will have blood drawn for immunologic assays.

-Personalized polyepitope inserts integrating the prioritized neoantigens and mesothelin epitopes will be designed and then synthesized and cloned into the pING parent vector

TDS-IM Electrode Array System

-Enrollment, mid adjuvant chemotherapy, end of chemotherapy, week 1, week 5, week 9, week 13, week 17, week 21, week 25, and week 77

Peripheral blood draws

William Gillanders, M.D.

Daniel Laheru, M.D.

This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen DNA vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen DNA vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be administered with an electroporation device. The hypothesis of this study is that neoantigen DNA vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.

-Subjects will be enrolled within 12 weeks of surgery and standard of care adjuvant chemotherapy will last approximately 12 weeks with an additional 12 weeks of standard of care adjuvant chemotherapy or adjuvant chemoradiation. The first vaccine may be administered following confirmation of disease-free status and within 60 days following date of repeat imaging. From time of enrollment to first vaccine could be up to 45 weeks.

Neoantigen DNA Vaccine in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy

A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Neoantigen DNA Vaccine Strategy in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy

* Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0
* Related indicates possibly, probably, or definitely related to the study treatment

Immunogenicity is defined as the number of participants with a neoantigen-specific immune response measured by ELISPOT analysis. A participant is considered a responder if there is a significant increase in the number of neoantigen-specific T cells to at least one neoantigen after vaccination. A significant increase is based on t-test comparing the number of neoantigen-specific T-cells before and after vaccination with p=0.05 for significance.

National Cancer Institute (NCI)

Personalized Neoantigen DNA Vaccine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Abdominal pain

Bruising

Chills

Conjunctivitis

Fatigue

Fever

Injection site pain

Injection site reaction

Hypertension

Muscle soreness

Myalgia

Nausea

Pain

Safety of Neoantigen DNA Vaccine as Measured by the Number of Subjects Experiencing Each Type of Treatment-related Adverse Event

Participants who are not included in this outcome measure include one who did not have enough tissue, one who had poor quality RNA and a vaccine could not be developed, and 2 who developed disease progression.

Immunogenicity of the Neoantigen DNA Vaccine as Measured by ELISPOT Analysis

The multiparametric flow cytometry assay described in the protocol was not sufficiently sensitive to reliably detect neoantigen-specific T cell responses. Additional flow cytometry assays are being performed as an exploratory objective.

Immunogenicity of the Neoantigen DNA Vaccine as Measured by Multiparametric Flow Cytometry

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors	NCT03988283	Pediatric Recur...	Personalized ne... Papivax Biotech... Peripheral bloo...	- 25 Years	Washington University School of Medicine
Neoantigen DNA Vaccine in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy	NCT03122106	Pancreatic Canc... Pancreas Cancer Cancer of the P...	Personalized ne... TDS-IM Electrod... Peripheral bloo...	18 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for personalized neoantigen dna vaccine