Trial Title:
Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease
NCT ID:
NCT06529822
Condition:
Muscle-Invasive Bladder Carcinoma
Conditions: Official terms:
Urinary Bladder Neoplasms
Nivolumab
Poly ICLC
Conditions: Keywords:
Personalized cancer vaccine
Solid tumor
Immunotherapy
Bladder cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Synthetic long peptide personalized cancer vaccine
Description:
Neoantigen vaccines will be provided on a patient-specific basis
Arm group label:
Cohort 1: Muscle Invasive Bladder Cancer (PCV)
Other name:
PCV
Intervention type:
Drug
Intervention name:
Poly ICLC
Description:
Poly-ICLC will be supplied by Oncovir, Inc.
Arm group label:
Cohort 1: Muscle Invasive Bladder Cancer (PCV)
Other name:
Hiltonol
Intervention type:
Biological
Intervention name:
Nivolumab
Description:
Standard of care, not required to be given by the protocol
Arm group label:
Cohort 1: Muscle Invasive Bladder Cancer (PCV)
Intervention type:
Device
Intervention name:
Signatera assay
Description:
Signatera is a clinically validated, personalized, tumor-informed, multiplex-PCR and
next-generation sequencing (NGS) based clinical trial assay targeting 16 tumor-specific
mutations. It is intended for the detection of ctDNA isolated from anticoagulated
peripheral whole blood from post-surgical patients previously diagnosed with localized or
advanced solid tumors to aid physician assessment and treatment decision-making, together
with other clinical factors
Arm group label:
Cohort 1: Muscle Invasive Bladder Cancer (PCV)
Summary:
This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity
of a personalized cancer vaccine strategy in patients with solid tumors and molecular
residual disease. The hypothesis of the trial is that synthetic long peptide personalized
cancer vaccines will be safe and capable of generating measurable neoantigen-specific
T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed
of synthetic long peptides corresponding to prioritized cancer neoantigens and will be
co-administered with poly-ICLC.
Criteria for eligibility:
Criteria:
Step 0 Inclusion Criteria:
- Age ≥ 18 years.
- Histologically confirmed muscle-invasive bladder cancer (MIBC).
- Patients with carcinomas showing mixed histologies are required to have a dominant
translational cell pattern.
- Tumor, nodes, metastases (TNM) classification (based on the American Joint Committee
on Cancer (AJCC) Cancer Staging Manual 8th ed.) at pathological examination of
surgical resection specimen as follows: pT2-4aN0M0 or pT0-4aN+M0
- Availability of a ctDNA report that is based on tumor tissue specimen and matched
blood.
- Radiologic confirmation (by conventional imaging) of absence of residual disease and
absence of metastasis no more than 28 days prior to enrollment.
- Ability to understand and willingness to sign an IRB approved written informed
consent document. Legally authorized representatives may sign and give informed
consent on behalf of study participants.
Step 0 Exclusion Criteria:
- Receiving any other investigational agents, or planning to receive other
investigational agents as part of neoadjuvant therapy.
- Known allergy, or history of serious adverse reaction to vaccines such as
anaphylaxis, hives, or respiratory difficulty.
- Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular,
hepatic renal, and/or other functional abnormality that might jeopardize the health
and safety of the participant as determined by the investigator based on medical
history, physical examination, laboratory values, and/or diagnostic studies. If
needed and appropriate. the final determination related to study eligibility prior
to the administration of the first vaccine will be documented by both the PI and
Sub-Investigators in consultation with a specialist.
- A psychiatric illness or social situations that would limit compliance with study
requirements as determined by the investigator from the medical history, physical
exam, and/or medical record.
- Prior or currently active autoimmune disease requiring management with
immunosuppression. This includes inflammatory bowel disease, ulcerative colitis,
Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis,
hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic
lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease
or any other medical condition or use of medication (e.g., corticosteroids) which
might make it difficult for the patient to complete the full course of treatments or
to generate an immune response to vaccines. In the case of asthma or chronic
obstructive pulmonary disease taking inhaled corticosteroids that does not require
daily systemic corticosteroids is acceptable. Additionally, local acting steroids
(topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or
short course steroids will be allow if the dose does not exceed 4 mg of
dexamethasone (or equivalent) per day for > 7 consecutive days. Premedication for
chemotherapy does not apply to this criterion and may be administered as per SOC
practice. Any patients receiving steroids should be discussed with the PI to
determine if eligible.
- Pregnant and/or breastfeeding.
- Known HIV-positive status.
- History of positive test for Hepatitis B virus surface antigen (HBsAg) and/or
positive Hepatitis C antibody result with detectable hepatitis C virus (HCV)
ribonucleic acid (RNA) indicating acute or chronic infection.
Step 1 Inclusion Criteria:
- ctDNA positive result as identified by Signatera.
- ECOG performance status ≤ 1 (Karnofsky ≥ 60%).
- Complete surgical resection of MIBC (R0).
- Full recovery from cystectomy and enrollment within 52 weeks following cystectomy.
- Adequate bone marrow and organ function as defined below:
- WBC ≥ 1.5 K/cumm
- Absolute neutrophil count ≥ 1.0 K/cumm
- Platelets ≥ 50 K/cumm
- Hemoglobin ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine clearance > 30 mL/min by Cockcroft-Gault
- The effects of synthetic long peptide personalized cancer vaccines, Hiltonol and
nivolumab on the developing human fetus are unknown. For this reason, women of
childbearing potential and men must agree to use adequate contraception prior to
study entry, for the duration of study participation, and for 5 months after
completion of study interventions and/or SOC nivolumab therapy. Should a woman
become pregnant or suspect she is pregnant while participating in this study or
should a man suspect he has fathered a child, s/he must inform her treating
physician immediately.
- Women of childbearing potential and men must agree to use two forms of adequate
contraception prior to study entry, for the duration of study participation, and for
3 months after completion of the study. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she must inform her treating
physician immediately.
- It is anticipated that patients will be treated with adjuvant nivolumab therapy
during personalized vaccine therapy. Of note, adjuvant nivolumab therapy is
considered standard of care in this patient population. No concurrent
investigational therapies outside of this protocol are allowed.
Step 1 Exclusion Criteria:
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Grade 1) with the exception of alopecia. For Step
1 Enrollment the patient must have completed all prior cancer treatments > 28 days
prior to vaccine administration with the exception of adjuvant nivolumab. No
concurrent investigational therapies allowed.
- History of immuno-oncology treatment for MIBC in the neoadjuvant setting. (It is
anticipated that patients will be treated with adjuvant nivolumab as per current SOC
and this is allowed).
- Prior or concurrent malignancy whose natural history has the potential to interfere
with the safety or efficacy assessment of the investigational regimen. Patients with
prior or concurrent malignancy that does NOT meet that definition are eligible for
this trial per discussion with the PI.
- Currently receiving any other investigational agents.
- Live vaccine administered within 30 days prior to enrollment.
- Known allergy, or history of serious adverse reaction to vaccines such as
anaphylaxis, hives, or respiratory difficulty.
- Immunodeficiency, systemic steroid therapy, or any other immunosuppressive therapy
within 30 days of enrollment.
- Active autoimmune disease (excluding diabetes mellitus and/or vitiligo), solid organ
or allogeneic bone marrow transplant, or other known contraindications to receiving
immunotherapy.
- Severe hypersensitivity (grade ≳ 3) to checkpoint inhibitors and/or any of its
excipients.
- Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular,
hepatic renal, and/or other functional abnormality that might jeopardize the health
and safety of the participant as determined by the investigator based on medical
history, physical examination, laboratory values, and/or diagnostic studies. If
needed and appropriate. the final determination related to study eligibility prior
to the administration of the first vaccine will be documented by both the PI and
Sub-Investigators in consultation with a specialist.
- A psychiatric illness or social situations that would limit compliance with study
requirements, as determined by the investigator from the medical history, physical
exam, and/or medical record.
- Current pneumonitis, a history of (non-infectious) pneumonitis requiring steroids,
or history of clinically significant interstitial lung disease.
- Active tuberculosis test within 3 months prior to treatment initiation.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
serum/urine pregnancy test within 14 days of study entry.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Contact:
Last name:
William Gillanders, M.D.
Phone:
314-747-0072
Email:
gillandersw@wustl.edu
Contact backup:
Last name:
Russell Pachynski, M.D.
Phone:
314-286-2341
Email:
rkpachynski@wustl.edu
Investigator:
Last name:
William Gillanders, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Russell Pachynski, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Malachi Griffith, Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Obi Griffith, Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Eric Knoche, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Peter Oppelt, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Joel Picus, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Melissa Reimers, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Robert Schreiber, Ph.D.
Email:
Sub-Investigator
Start date:
November 30, 2024
Completion date:
May 31, 2033
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Natera, Inc.
Agency class:
Industry
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06529822
http://www.siteman.wustl.edu
