PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)
About this trial
Background:
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 PLX038 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Recurrent or progressive MYCN amplified ependymoma, OR
Recurrent or progressive medulloblastoma with MYC or MYCN amplifications
Disqualifiers
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://drug-interactions.medicine.iu.edu/maintable.
History of treatment with pegylated topoisomerase inhibitors.
Trial design
Design model
Sequential
Treatments tested in this trial
PLX038
DrugPLX038 is given intravenously (IV) at the assigned dose level over about 1 hour on day 1 of each 21-day cycle
Treatment groups
146 Participants
are divided into 2 treatment groupsGroup A: Phase IExperimental treatment 1 intervention
Group B: Phase IIExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Phase I: To confirm the RP2D of PLX038 in participants with progressive or recurrent primary CNS tumors
Number of Dose Limiting Toxicities (DLT).
Time frame
Days 1-42 (cycles 1-2)2
Phase II: To assess the efficacy of PLX038 at RP2D in primary CNS tumors containing MYC or MYCN amplifications
Adjuvant cohort: Defined as the time from the PLX038 treatment start date to the date of confirmed progression/death or last follow-up. Kaplan-Meier method will be used to estimate the survival function. The median PFS as well as the 95% CI will be summarized.Recurrent cohorts: Defined as the percentage of participants having CR, PR, or SD \>= 6 months as determined by investigator per RANO and/or RECIST v1.1. The DCR and its 95% exact binomial CI will be summarized.
Time frame
5 yearsSecondary outcomes
1
Determine overall survival (OS)
Measured the time from the start of PLX038 treatment to the date of death or last follow-up. OS will be estimated using the methods of Kaplan and Meier. The median OS and its 95%CI will be summarized. (All cohorts)
Time frame
5 years2
Determine progression free survival (PFS)
Defined as the time from the PLX038 treatment start date to the date of conformed progression/death or last follow-up. Kaplan-Meier method will be used to estimate the survival function. The median PFS as well as the 95% CI will be summarized. (Recurrent cohorts)
Time frame
5 years3
Determine the treatment-related toxicities
Clinical safety data (i.e., vital signs, ECGs, routine laboratory tests, physical examinations, and AEs) will be summarized using descriptive statistics (e.g., mean, frequency) using the safety analysis set (SAS). All the toxicity data will be summarized by dose level and by cohort.
Time frame
Days 1-604
Longitudinally evaluate patient reported outcomes (PRO)
Feasibility of PRO data collection for each questionnaire will be evaluated by calculating the compliance rates which is the number of received valid forms over the number of expected forms. Analysis of results will be based upon each separate questionnaire type to determine meaningful change.
Time frame
5 yearsSponsors and contacts
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Source ClinicalTrials.gov