Phase 1
N=33
Nanoparticle Albumin-Bound Rapamycin, Temozolomide, and Irinotecan Hydrochloride in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors
Childhood Solid Neoplasm · Recurrent Malignant Solid Neoplasm · Recurrent Primary Central Nervous System Neoplasm · Refractory Malignant Solid Neoplasm · Refractory Primary Central Nervous System Neoplasm
Bottom Line
View on ClinicalTrials.gov: NCT02975882 ↗Enrolled (actual)
33
Serious AEs
90.6%
Results posted
Mar 2023
Primary outcome: Primary: Number of Patients With Cycle 1 and 2 Dose Limiting Toxicities Attributable to Nanoparticle Albumin-bound Rapamycin — 1; 2; 1; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Irinotecan Hydrochloride (Drug); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Sirolimus Albumin-bound Nanoparticles (Drug); Temozolomide (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Mar 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Cycle 1 and 2 Dose Limiting Toxicities Attributable to Nanoparticle Albumin-bound Rapamycin |
1; 2; 1; 1 | — |
| PRIMARY Number of Patients With Adverse Events |
4; 12; 8; 5 | — |
| PRIMARY Area Under the Serum of Nanoparticle Albumin-bound Rapamycin Concentration Curve |
13654; 9532; 8666; 7988.5 | — |
| SECONDARY Number of Patients With Antitumor Activity of Nanoparticle Albumin-bound Rapamycin |
1; 0; 0; 0 | — |
Summary
This phase I trial studies the side effects and best dose of nanoparticle albumin-bound rapamycin when given together with temozolomide and irinotecan hydrochloride in treating pediatric patients with solid tumors that have come back after treatment and a period of time during which the tumor could not be detected or has not responded to treatment. Nanoparticle albumin-bound rapamycin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide and irinotecan hydrochloride, 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. Giving nanoparticle albumin-bound rapamycin, temozolomide, and irinotecan hydrochloride may cause the cancer to stop growing or shrink for a period of time and may lessen the symptoms that are caused by the cancer.
Eligibility Criteria
Inclusion Criteria
- Patients must have a body surface area (BSA) of >= 0.2 m^2 at the time of study enrollment
- Patients with recurrent or refractory solid tumors, including 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)
- Patients must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients = = 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
- Antibodies: >= 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
- Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
- Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
- Stem cell infusions (with or without total body irradiation [TBI]):
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion, and no evidence of graft-versus-host disease (GVHD)
- Autologous stem cell infusion including boost infusion: >= 42 days
- Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
- X ray (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
- Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131 iodine metaiodobenzylguanidine [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
- Irinotecan, temozolomide and mammalian target of rapamycin (mTOR) inhibitor exposure:
- Patients who have received prior single agent therapy with irinotecan, temozolomide, or an mTOR inhibitor, excluding ABI-009, are eligible
- Patients who have received prior therapy with ABI-009 are not eligible
- Patients who have previously received irinotecan and temozolomide in combination without progressive disease while on therapy are eligible
- Patients who have previously received irinotecan and temozolomide in combination and had significant toxicity with these two drugs are not eligible
- Patients who have received prior therapy with all three agents in combination (i.e. irinotecan, temozolomide, and an mTOR inhibitor) are not eligible
- Adequate Bone Marrow Function Defined as:
- For patients with solid tumors without known bone marrow involvement (no older than 7 days at the start of therapy):
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100,0
Data sourced from ClinicalTrials.gov (NCT02975882). 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.