Phase 1
N=59
Selinexor in Treating Younger Patients With Recurrent or Refractory Solid Tumors or High-Grade Gliomas
Malignant Glioma · Recurrent Brain Neoplasm · Recurrent Childhood Central Nervous System Neoplasm · Recurrent Childhood Glioblastoma · Recurrent Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT02323880 ↗Enrolled (actual)
59
Serious AEs
33.9%
Results posted
Jan 2024
Primary outcome: Primary: Number of Dose Limiting Toxicities of Selinexor — 0; 4; 1; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Pharmacological Study (Other); Selinexor (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Dose Limiting Toxicities of Selinexor |
0; 4; 1; 2; 1; 0 | — |
| PRIMARY Number of Adverse Events of Selinexor |
6; 12; 6; 6; 6; 7 | — |
| PRIMARY Area Under the Drug Concentration Curve of Selinexor |
5030; 4656.8; 2602.4; 6173.2; 7135.9; 4666.9 | — |
| SECONDARY Antitumor Effect of Selinexor |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Pharmacodynamics of Selinexor |
7.1; 4; 5.5; 1.7; 4.6; 7.9 | — |
| SECONDARY Pharmacodynamics of Selinexor in High-grade Glioma (HGG) Patients |
4.2; 4.6; 5.9 | — |
| SECONDARY Radiographic Response of Selinexor in High-grade Glioma (HGG) Patients |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Progression-free Survival of Selinexor in Surgical High-grade Glioma (HGG) Patients |
0; 0; 0; 0; 0; 0 | — |
Summary
This phase I trial studies the side effects and best dose of selinexor in treating younger patients with solid tumors or central nervous system (CNS) tumors that have come back (recurrent) or do not respond to treatment (refractory). Drugs used in chemotherapy, such as selinexor, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Eligibility Criteria
Inclusion Criteria
- Patients must have a body surface area (BSA) >= 0.84 m^2
- Diagnosis:
- Part A: Patients with recurrent or refractory solid tumors, including lymphoma and CNS tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
- Part B: Patients with recurrent or refractory high grade glioma (World Health Organization [WHO] grade III/IV) including disseminated tumors (excluding diffuse intrinsic pontine glioma [DIPG]), not requiring surgical resection; patients must have had histologic verification of malignancy at original diagnosis or relapse
- Part C: Patients with recurrent or refractory high grade glioma (WHO grade III/IV) and requiring surgical resection (excluding DIPG and disseminated tumors), who in the opinion of treating physicians, are medically stable to receive 2 doses of selinexor (8-10 days of treatment) before undergoing surgery without compromising the success of the procedure; note that if, in the opinion of treating physicians, current symptoms necessitate surgery before 2 doses will be able to be received, surgery should not be delayed to administer selinexor, and the patient would be ineligible for protocol therapy
- Disease status:
- Part A: Patients must have either measurable or evaluable disease
- Parts B and C: Patients must have measurable disease on imaging
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients = = 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade = = 14 days must have elapsed since last dose of corticosteroid
- External beam radiation therapy (XRT): At least 14 days after local palliative XRT (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
- Stem cell infusion without TBI: No evidence of active graft vs. host disease and at least 56 days must have elapsed after transplant or stem cell infusion
- Patients must not have received prior exposure to selinexor
- For patients with solid tumors without known bone marrow involvement:
- * Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- * Platelet count >= 100, 000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- * Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
- Patients with known bone marrow metastatic disease will be eligible for study if they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or
- A serum creatinine based on age/gender as follows:
- = = 13 years)
- = = 16 years)
- Total bilirubin = = 2 g/dL
- Serum amylase = = 14 days must have elapsed since last dose of corticosteroid
- Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
- Anti-cancer agents: Patients who are currently receiving other anti-cancer agen
Data sourced from ClinicalTrials.gov (NCT02323880). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.