Difluoromethylornithine (DFMO) and AMXT-1501 for Neuroblastoma, CNS Tumors, and Sarcomas

Launched by MILTON S. HERSHEY MEDICAL CENTER · Jun 13, 2024

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment for children and young adults with certain types of cancer, including neuroblastoma, brain tumors like DIPG, and specific sarcomas. The study is testing a combination of two drugs: AMXT-1501, which is a pill taken by mouth, and DFMO, which is given through an IV. The main goals are to find out the best dose of AMXT-1501 to use with DFMO, check how safe this combination is, and see how well it works in helping patients respond to treatment and live longer without their cancer worsening.

To be eligible for this trial, participants must be between 0 and 21 years old and have specific types of tumors that have either come back or have not responded well to previous treatments. They need to be well enough to take these medications and must have recovered from any serious side effects of prior cancer treatments. The trial is not yet recruiting participants, but once it starts, those who join can expect careful monitoring of their health and well-being throughout the study. This is an important step in finding new options for young patients facing tough cancer challenges.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age: 0-21 years of age at diagnosis
• • 2. Pathology
• All subjects must have a confirmed pathologic diagnosis of tumor type (except for DIPG):
• • Relapsed/Refractory Neuroblastoma
• • Embryonal tumor with multilayer rosettes (ETMR)
• • Atypical teratoid rhabdoid tumor (ATRT)
• • Diffuse Intrinsic Pontine Glioma (DIPG)- radiologic diagnosis
• • Relapsed/refractory Ewing Sarcoma
• • Relapsed/refractory Osteosarcoma
• 3. Tumor assessment:
• • Disease staging must be performed. This disease assessment is required for eligibility and must be done within a maximum of 4 weeks before first dose of study drug.
• 4. Disease Status:
• • Relapsed/Refractory Neuroblastoma Known high-risk neuroblastoma or previously intermediate-risk neuroblastoma that has relapsed or progressed to high-risk with failure to achieve CR with standard therapy (defined as at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol) or Known high-risk neuroblastoma or previously intermediate-risk neuroblastoma in a 2nd or greater remission
• • Relapsed/refractory ETMR/ATRT Subjects that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive/progressive to accepted curative therapy, including up-front chemotherapy and radiation and/or high-dose chemotherapy with stem cell rescue.
• • Diffuse Intrinsic Pontine Glioma (DIPG) Subjects with DIPG to start greater than 30 days, and no longer than 60 days, after standard of care radiation therapy. Subjects with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of the pons on at least 1 axial T2-weighted image, are eligible. No histologic confirmation is required. Subjects with metastatic disease are not eligible. Subjects with a biopsy and no evidence of H3K27m mutations are eligible as long as they meet radiographic criteria. Subjects with H3K27m altered DMG outside of the brainstem are not eligible. Subjects with progression or recurrence after initial standard of care radiation are ineligible.
• • Relapsed/refractory Ewing Sarcoma and Osteosarcoma Subjects that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for Ewing sarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy.
• • 5. Subjects must be able to swallow capsules.
• • 6. Subjects must not have progressed while taking any previous DFMO prior to this study.
• • 7. Subjects with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week and must not have progressive hydrocephalus at enrollment.
• 8. Timing from prior therapy:
• Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
• • 1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
• • 2. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. 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.
• • 3. Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells except for anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc) which should be at least 2 weeks since prior treatment with a monoclonal antibody.
• • 4. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
• • Note: Subjects with DIPG will be required to have had up front standard of care radiation. As above, subjects with DIPG must be between 30-60 days post initial up front radiation therapy.
• 5. Stem Cell Transplant:
• • 1. Allogeneic: No evidence of active graft vs. host disease
• • 2. Allo/Auto: ≥ 2 months must have elapsed since transplant.
• • 6. MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.
• • 9. Subjects must have a Lansky or Karnofsky Performance Scale score of \>/= 50
• 10. Subjects must have adequate organ function at the time of enrollment:
• • Hematological: Hematological recovery as defined by ANC ≥750/μL
• • Liver: Adequate liver function as defined by AST and ALT \<10x upper limit of normal
• • Renal: Subjects must have adequate renal function defined as Creatinine clearance (in units ml/min) or radioisotope GFR ≥ 70 The formula to be used : Adjusted GFR=(Estimated GFR×BSA / 1.73)mL/min
• • 11. Subjects of childbearing potential must have a negative pregnancy test. Subjects of childbearing potential must agree to use an effective birth control method. Subjects who are lactating must agree to stop breast-feeding.
• • 12. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).
• Exclusion Criteria:
• • 1. BSA of \<0.25 m2
• • 2. Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• • 3. Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.
• • 4. Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• • 5. Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.