This study is currently recruiting participants.
Number
001534-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Children;Fetuses;Neonates
Keywords
Brain Tumors; Recurrent or progressive primary CNS tumors; Patient-Reported Outcomes; Spine Tumors; MYC or MYCN genes
Recruitment Keyword(s)
None
Condition(s)
Glioma; Medulloblastoma; Ependymoma
Investigational Drug(s)
PLX038 (pegylated SN-308 conjugate PLX038)
Investigational Device(s)
Intervention(s)
Drug: PLX038
Supporting Site
National Cancer Institute
About 90,000 new cases of brain and spinal cord tumors are diagnosed annually in the United States. Most of these tumors are benign; however, about 30% are malignant, and 35% of people with malignant tumors in the brain and spinal cord will die within 5 years. Many of these people have changes in certain genes (MYC or MYCN) that drive the development of their cancers.
Objective:
To test a study drug (PLX038) in people with tumors of the brain or spinal cord.
Eligibility:
People aged 18 years or older with a tumor of the brain or spinal cord. Some participants must also have tumors with changes in the MYC or MYCN genes.
Design:
Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and a test of their heart function. They may need to have a biopsy: A sample of tissue will be removed from their tumor.
PLX038 is given through a tube attached to a needle inserted into a vein in the arm. All participants will receive PCX038 on the first day of each 21-day treatment cycle. They will take a second drug 3 days later to help reduce the risk of infection; for this drug, participants will be shown how to inject themselves under the skin at home.
Blood tests, imaging scans, and other tests will be repeated during study visits. Hair samples will also be collected during these visits. Some participants may have an additional biopsy.
Study treatment will continue up to 7 months.
Follow-up visits will continue every few months for up to 5 years.
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INCLUSION CRITERIA: -Participants must have histologically confirmed by NCI Laboratory of Pathology (LP) primary central nervous system (CNS) tumor with one of the below diagnoses: --Cohort Phase I: Any recurrent or progressive primary CNS tumor, regardless of molecular features. --Cohort Phase IIA: Newly diagnosed MYCN amplified ependymoma after surgery and radiation. --Cohort Phase IIB: ---Recurrent or progressive MYCN amplified ependymoma, OR ---Recurrent or progressive medulloblastoma with MYC or MYCN amplifications --Cohort Phase IIC: Any other recurrent or progressive primary CNS tumor with MYC or MYCN amplifications. NOTE 1: Recurrence or progression may involve CNS, extra CNS, or both. NOTE 2: The presence of MYCN or MYC amplification will be determined by NSR device (via next generation sequencing panel TSO500) and the threshold of MYCN or MYC amplification for eligibility purposes is a fold change (FC) of >= 2.5X (5 copies) with a minimum tumor content of 20%. -Participants must have archival tumor tissue (either a block or 20 formalin-fixed paraffin-embedded (FFPE) unstained slides) available for NCI LP review and confirmation of diagnosis: --Cohorts Phase I, Phase IIB, and Phase IIC: tumor tissue obtained at any point before trial treatment initiation, but preferably from most recent surgical resection before study treatment initiation. --Cohort Phase IIA: tumor tissue obtained at original diagnosis. -Participants in Cohort Phase IIA must have completed surgery followed by radiation at least 4 weeks and no more than 10 weeks from the last dose of radiation prior to study treatment initiation. -Participants in Cohorts Phase I, Phase IIB, and Phase IIC must have completed prior cytotoxic chemotherapy or radiation at least 4 weeks prior to study treatment initiation (at least 6 weeks if the last regimen included lomustine (CCNU) or carmustine (BCNU); at least 3 weeks if the last regimen included bevacizumab; at least 5 half-lives if the last regimen included any investigational agent(s). Participants previously treated with PHOTON radiation to at least 2 segments of the spine must have completed radiation at least 12 months before study treatment initiation. -Age >= 18 years. -Karnofsky >= 70% (Cares for self, unable to carry on normal activity or to do active work.) NOTE: Participants with severe paraparesis/paraplegia who need minimal assistance for self-care due to their motor deficit but are otherwise functionally independent will be eligible. -Participants must have adequate organ and marrow function as defined below: --leukocytes >4=3,000/microliter --absolute neutrophil count >1,500/microliter --platelets >100,000/microliter --hemoglobin >= 9 g/ dL (may be transfused within 2 weeks prior to treatment to achieve this level) --total bilirubin within normal institutional limits --aspartate aminotransferase (AST) / alanine aminotransferase (ALT) <2.5 X institutional upper limit of normal (ULN) --creatinine within normal institutional limits OR estimated glomerular filtrate rate (eGFR) using chronic kidney disease epidemiology collaboration) (CKD-EPI) equation:within normal institutional limits OR >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal -Women of child-bearing potential (WOCBP) and men must agree to use effective contraception (barrier, hormonal contraception, intrauterine device (IUD), surgical sterilization for women, barrier, surgical sterilization for men) at the study entry, for the duration of study treatment and up to 6 months (women) and 3 months (men) after the last dose of study treatment. -Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after the last dose of the study drug. -Ability to self-report symptoms and physical function as determined by assessment of the clinical team performed at screening. -Participants must be able to understand and willing to sign a written informed consent document. EXCLUSION CRITERIA: -History of allergic reactions to compounds of similar chemical composition to PLX038. -Major surgery within 2 weeks prior to study treatment initiation. NOTE: The surgery is considered major if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges). -Participants who require treatment with strong inhibitors or inducers of CYP3A or with UGT1A1 inhibitors during the planned period of investigational treatment with PLX038. Lists including medications and substances known or with the potential to interact with CYP3A or UGT1A1 are provided in https://www.fda.gov/drugs/drug-interactionslabeling/drug-development-and-drug-interactions-table-substrates-inhibitors-andinducers. -History of treatment with pegylated topoisomerase inhibitors. -History of treatment with PHOTON craniospinal irradiation (CSI). -Participants with history of homozygous for the UGT1A1*28 variant allele with severely reduced UGT1A1 activity. -Participants positive for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV). -Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening). -Participants unable to have MRIs. -Prior or concurrent malignancy unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (https://deainfo.nci.nih.gov/advisory/ctac/1117/4-JournalClinicalOncology.pdf, https://ctep.cancer.gov/protocolDevelopment/docs/CTEP_Broadened_Eligibility_Criteria_Guidance.pdf) -Uncontrolled intercurrent illness evaluated by history, weight, and physical exam that would limit compliance with study requirements.
-Participants must have histologically confirmed by NCI Laboratory of Pathology (LP) primary central nervous system (CNS) tumor with one of the below diagnoses:
--Cohort Phase I: Any recurrent or progressive primary CNS tumor, regardless of molecular features.
--Cohort Phase IIA: Newly diagnosed MYCN amplified ependymoma after surgery and radiation.
--Cohort Phase IIB:
---Recurrent or progressive MYCN amplified ependymoma, OR
---Recurrent or progressive medulloblastoma with MYC or MYCN amplifications
--Cohort Phase IIC: Any other recurrent or progressive primary CNS tumor with MYC or MYCN amplifications.
NOTE 1: Recurrence or progression may involve CNS, extra CNS, or both.
NOTE 2: The presence of MYCN or MYC amplification will be determined by NSR device (via next generation sequencing panel TSO500) and the threshold of MYCN or MYC amplification for eligibility purposes is a fold change (FC) of >= 2.5X (5 copies) with a minimum tumor content of 20%.
-Participants must have archival tumor tissue (either a block or 20 formalin-fixed paraffin-embedded (FFPE) unstained slides) available for NCI LP review and confirmation of diagnosis:
--Cohorts Phase I, Phase IIB, and Phase IIC: tumor tissue obtained at any point before trial treatment initiation, but preferably from most recent surgical resection before study treatment initiation.
--Cohort Phase IIA: tumor tissue obtained at original diagnosis.
-Participants in Cohort Phase IIA must have completed surgery followed by radiation at least 4 weeks and no more than 10 weeks from the last dose of radiation prior to study treatment initiation.
-Participants in Cohorts Phase I, Phase IIB, and Phase IIC must have completed prior cytotoxic chemotherapy or radiation at least 4 weeks prior to study treatment initiation (at least 6 weeks if the last regimen included lomustine (CCNU) or carmustine (BCNU); at least 3 weeks if the last regimen included bevacizumab; at least 5 half-lives if the last regimen included any investigational agent(s). Participants previously treated with PHOTON radiation to at least 2 segments of the spine must have completed radiation at least 12 months before study treatment initiation.
-Age >= 18 years.
-Karnofsky >= 70% (Cares for self, unable to carry on normal activity or to do active work.) NOTE: Participants with severe paraparesis/paraplegia who need minimal assistance for self-care due to their motor deficit but are otherwise functionally independent will be eligible.
-Participants must have adequate organ and marrow function as defined below:
--leukocytes >4=3,000/microliter
--absolute neutrophil count >1,500/microliter
--platelets >100,000/microliter
--hemoglobin >= 9 g/ dL (may be transfused within 2 weeks prior to treatment to achieve this level)
--total bilirubin within normal institutional limits
--aspartate aminotransferase (AST) / alanine aminotransferase (ALT) <2.5 X institutional upper limit of normal (ULN)
--creatinine within normal institutional limits OR estimated glomerular filtrate rate (eGFR) using chronic kidney disease epidemiology collaboration) (CKD-EPI) equation:within normal institutional limits OR >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
-Women of child-bearing potential (WOCBP) and men must agree to use effective contraception (barrier, hormonal contraception, intrauterine device (IUD), surgical sterilization for women, barrier, surgical sterilization for men) at the study entry, for the duration of study treatment and up to 6 months (women) and 3 months (men) after the last dose of study treatment.
-Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after the last dose of the study drug.
-Ability to self-report symptoms and physical function as determined by assessment of the clinical team performed at screening.
-Participants must be able to understand and willing to sign a written informed consent document.
EXCLUSION CRITERIA:
-History of allergic reactions to compounds of similar chemical composition to PLX038.
-Major surgery within 2 weeks prior to study treatment initiation. NOTE: The surgery is considered major if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges).
-Participants who require treatment with strong inhibitors or inducers of CYP3A or with UGT1A1 inhibitors during the planned period of investigational treatment with PLX038. Lists including medications and substances known or with the potential to interact with CYP3A or UGT1A1 are provided in https://www.fda.gov/drugs/drug-interactionslabeling/drug-development-and-drug-interactions-table-substrates-inhibitors-andinducers.
-History of treatment with pegylated topoisomerase inhibitors.
-History of treatment with PHOTON craniospinal irradiation (CSI).
-Participants with history of homozygous for the UGT1A1*28 variant allele with severely reduced UGT1A1 activity.
-Participants positive for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV).
-Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening).
-Participants unable to have MRIs.
-Prior or concurrent malignancy unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (https://deainfo.nci.nih.gov/advisory/ctac/1117/4-JournalClinicalOncology.pdf, https://ctep.cancer.gov/protocolDevelopment/docs/CTEP_Broadened_Eligibility_Criteria_Guidance.pdf)
-Uncontrolled intercurrent illness evaluated by history, weight, and physical exam that would limit compliance with study requirements.
Principal Investigator
Referral Contact
For more information: