Clinical trial for Adult Glioblastoma
Official title A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM)
ClinicalTrials.gov ID: NCT04573140
What this study is testing
What is Autologous total tumor mRNA and pp65 full length (fl) lysosomal associated membrane protein (LAMP) mRNA loaded DOTAP liposome vaccine?
An investigational intravenous RNA‑liposome vaccine being studied as a potential treatment for adult glioblastoma.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The study aims to see if the vaccine can be safely made and to find the highest dose that patients can tolerate.
- Who it's for
- Adults with newly diagnosed glioblastoma that have low or unmethylated MGMT, and children with newly diagnosed high‑grade glioma.
- What's involved
- Participants will receive the RNA‑lipid particle vaccine at increasing dose levels and will have regular clinic visits for safety checks and lab tests.
- Time commitment
- The trial runs for several months and includes multiple visits to the study site for dosing and monitoring.
- Phase 1: an early, usually small safety study
- Time commitment: about 14 months
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 4 and older
You may be able to join if
- Stratum 1 (Adult GBM)
- Age ≥ 21 years.
- Histopathologically proven newly-diagnosed de novo GBM (WHO Grade IV glioma, secondary GBM not eligible) that is MGMT low level or unmethylated.
- The tumor must have a supratentorial component.
- Patient must have been enrolled on a screening consent and have had sterile collection of tumor material in a manner suitable for RNA extraction...
You likely can't join if
- Stratum 1 (Adult GBM)
- Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years.
- MGMT Methylated tumors
- Gliomatosis Cerebri
- Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal involvement.
- Recurrent or multifocal malignant gliomas.
See the full eligibility criteria
Who can join
- Stratum 1 (Adult GBM)
- Age ≥ 21 years.
- Histopathologically proven newly-diagnosed de novo GBM (WHO Grade IV glioma, secondary GBM not eligible) that is MGMT low level or unmethylated.
- The tumor must have a supratentorial component.
- Patient must have been enrolled on a screening consent and have had sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs).
- Residual post-surgical disease burden ≤ 3 cm as defined by longest perpendicular diameter of tumor on post-operative MRI.
- Patients must have recovered from the effects of surgery, postoperative infection, and other complications.
- A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment.
- Performance Score: (KPS) ≥ 60. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- ANC (Absolute neutrophil count) ≥ 1,000µl (unsupported)
- Platelets ≥ 150/µl (unsupported for at least 7 days)
- Hemoglobin \> 8 g/dL
- BUN ≤ 25 mg/dl
- Creatinine ≤ 1.7 mg/dl
- Hepatic
- Bilirubin ≤ 2.0 mg/dl
- ALT ≤ 5 times institutional upper limits of normal for age
- AST ≤ 5 times institutional upper limits of normal for age
- Willing to take an antiepileptic medication such as levetiracetam for the duration of RNA-LP vaccinations
- Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the legally authorized representative.
- For women of childbearing potential (WOCBP), negative serum/urine pregnancy test at enrollment (test will be repeated within 72 hours prior to starting TMZ in Stratum 1 patients).
- WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
- Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24...
- Participants with post-surgical neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. Stratum 2 (Newly-diagnosed Pediatric HGG)
- Age \> 3 and ≤ 25 years.
- Histologically confirmed WHO Grade III or IV malignant glioma
- Patient must have been enrolled on a screening consent and have had sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs).
- Residual post-surgical disease burden ≤ 3 cm as defined by longest diameter of tumor on post-operative MRI.
- Patients must have recovered from the effects of surgery, postoperative infection, and other complications.
- A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment.
- Performance Score: Karnofsky ≥ 60 for participants \> 16 years of age and Lansky ≥ 60 for participants \< 16 years of age assessed within 2 weeks prior to enrollment.
- ANC (Absolute neutrophil count) ≥ 1,000/µl (unsupported)
- Platelets ≥ 100/µl (unsupported for at least 7 days)
- Hemoglobin \> 8 g/dL (may be supported)
- Renal: Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or acceptable serum creatinine based on age/gender
- Bilirubin ≤ 3 times upper limit of institutional normal for age.
- SGPT (ALT) ≤ 5 times upper limit of institutional normal for age.
- SGOT (AST) ≤ 5 times upper limit of institutional normal for age.
- Participants who are receiving systemically-administered steroids must be on a stable or decreasing dose for \>1 week prior to enrollment.
- Willing to take an antiepileptic medication such as levetiracetam for the duration of RNA-LP vaccinations.
- A legal parent/guardian or patient must be able to understand and be willing to sign a written informed consent and assent document, as appropriate.
- For women of childbearing potential (WOCBP), negative serum/urine pregnancy test at enrollment
- WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
- Males of child-fathering potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the...
- Participants with post-surgical neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment.
- Patients must be enrolled on PNOC COMP prior to enrollment on PNOC020 if PNOC COMP is open to accrual at the enrolling institution.
What rules you out
- Stratum 1 (Adult GBM)
- Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible.)
- MGMT Methylated tumors
- Gliomatosis Cerebri
- Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal involvement.
- Recurrent or multifocal malignant gliomas.
- Metastatic or leptomeningeal disease
- Residual post-surgical disease burden \> 3 cm as defined by longest perpendicular diameter on MRI.
- Known HIV, Hepatitis B, or Hepatitis C seropositive.
- Known active infection or immunosuppressive disease.
- Participants who require corticosteroids above physiologic doses or not weaned to physiologic dosing within 1 week of scheduled vaccination.
- Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the head and neck region, other than TMZ prescribed during radiation for GBM (prior chemotherapy for a different cancer is allowable).
- Prior radiotherapy to the head or neck, resulting in overlap of radiation fields. Radiosurgery is not permitted.
- Unstable angina and/or congestive heart failure requiring hospitalization.
- Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months.
- Acute bacterial or fungal infection requiring intravenous antibiotics at initiation of XRT/TMZ.
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at initiation of XRT/TMZ.
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly...
- Patients with autoimmune disease requiring medical management with immunosuppressants.
- Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.
- Active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity.
- Pregnancy or women of childbearing potential and men who are sexually active and who are unwilling or unable to use an acceptable method of contraception for the entire study period
- Women of childbearing potential must not be pregnant or breast-feeding.
- Prior history of brachial neuritis or Guillain-Barré syndrome.
- Participants who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to study entry.
- Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations Stratum 2 (Pediatric HGG)
- Diffuse intrinsic pontine glioma, brainstem diffuse midline glioma, or BRAFV600E+
- Tumor with evidence of clinically significant uncal herniation, midline shift, tonsillar herniation, or brainstem infiltration, or that shows significant mass effect in either brain or spine
- Tumor with extensive and diffuse multilobular involvement (\>3 lobes)
- Tumor with extracranial disease
- Known HIV, Hepatitis B, or Hepatitis C seropositive.
- Uncontrolled seizure disorder
- History of myocarditis
- Receipt of any live vaccine within 30 days prior to enrollment
- Known active infection or immunosuppressive disease.
- Participants with significant renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), pulmonary, hepatic or other organ dysfunction.
- Severe or unstable concurrent medical conditions.
- Women must not be pregnant or breast-feeding.
- Participants who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to study entry.
- Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations.
The study team makes the final eligibility decision.
Where it is enrolling
- Washington D.C., District of Columbia, United States
- Gainesville, Florida, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The study runs about 14 months per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 4 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Washington D.C., District of Columbia, United States; Gainesville, Florida, United States. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.