None listed
Conditions
Brief summary
The purpose of this study is to figure out the ideal dosing schedule for a new chemotherapy medication called ACT001. Who is it for? You may be eligible for this study if you are aged between 1 and 21 years and have brain cancer or another solid tumour. Study details Participants will take capsules of the study medication, either dissolved in apple juice or as tablets, twice per day for 28 days. The amount of medication taken will depend on the results of participants before you. All participants will provide blood samples and have CT and MRI scans. It is hoped this research will find better treatment option for children with advanced brain and solid tumours.
Interventions
ACT001 self administration will be done twice-daily, in the morning and in the evening, separated by approximately 12 hours and within 30 minutes of completing a meal or snack. Patients will self administer ACT001 orally with a full cup (approximately 240 mL) of noncarbonated room temperature water. Additional water is permitted, if needed, with a maximum of 480 mL.
Alternatively, capsules are able to be opened and dissolved in apple juice with mixing. 100mg ACT001 is well dissolved in 1ml appl
ACT001 self administration will be done twice-daily, in the morning and in the evening, separated by approximately 12 hours and within 30 minutes of completing a meal or snack. Patients will self administer ACT001 orally with a full cup (approximately 240 mL) of noncarbonated room temperature water. Additional water is permitted, if needed, with a maximum of 480 mL. Alternatively, capsules are able to be opened and dissolved in apple juice with mixing. 100mg ACT001 is well dissolved in 1ml apple juice and is stable at room temperature (25oC) for 24h or at 2-8oC for 10 days. The study has two parts: a. Part A This part of the study will seek to identify the MTD in children with advanced brain or solid tumors. The starting dose will be 80% of the adult RP2D based on body surface area. Evaluation of a cohort of at least three (3) patients completing one cycle of treatment at that dose level is required prior to determining the dose level and dose regimen for the next cohort. If 80% of the adult RP2D is not tolerated, 50% the adult RP2D will be investigated. One cycle has a duration of 28 days. Participants will undergo in one dose level only. Dose Level mg/m2 -1 (de-escalation) at 117.5 mg/m2 twice a day 1 - starting dose at 118 mg/m2 twice a day 2 - 425mg/m2 twice a day 3 - 530 mg/m2 twice a day 4 - 700 mg/ m2 twice a day 5 - 875 mg/m2 twice a day Study duration for participants in the active treatment phase will consist of 2 weeks for completion of screening and up to 24 months of treatment depending on the disease state and tolerability to ACT001 in addition to a safety follow-up visit within 28 days of the last dose. If a patient has a sustained clinical / radiological response by RECIST criteria they may continue ACT001 treatment until they experience an unacceptable adverse event, disease progression or they wish to withdraw consent. Patients will discontinue study drug if there is radiologic evidence of progression unless the investigator determines that the patient is likely to derive benefit from continuing treatment with the study drug. Continuation of treatment beyond 24 months may be considered, if patients are receiving clinical benefit from the study, at the discretion of the Sponsor. The decision to continue on study should be made by the treating physician and the patient/parent/guardian in consultation with the study chair. If a patient is noted to still have ongoing toxicities at the 30 day safety follow-up visit, they will then be evaluated every 30 days until the toxicity(s) resolves to baseline, stabilizes or is deemed irreversible. After discontinuation of the active treatment phase, patients will be requested to participate in long term follow-up to assess overall survival. Contact will be made with patient/parent/guardians approximately every 3 months from ending active participation. Long term follow-up will continue for at least 12 months after the last patient is enrolled in the study. Patient/parent/guardians who withdraw full consent will not participate in the long term follow-up. Part B The dose expansion phase will involve enrolling an additional 10 patients at the ACT001 Recommended Phase II Dose (RP2D) as defined in Part A. The same Enrolment in Part B will be restricted to children with DIPG, Diffuse Midline H3 K27M glioma post RT, or other high grade glioma after recurrence or progression. The dosing frequency, duration and mode of administration of ACT001 will follow the same procedures as Part A. Patient Diary will be utilized for both Parts A and B to monitor adherence to intervention.
Sponsors
Accendatech AU Pty Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. All patients and/or their parents or legal guardians must give voluntary written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. 2. Aged =/> 1year and =/> 21 years old at the time of study enrolment. 3. Karnofsky =/> 50% for patients > 16years of age and Lansky =/> 50% for patients =/> 16 years of age. a. Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrolment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score. b. Patients receiving corticosteroids must be on a stable dose that has not been increased for at least 7 days prior to study enrolment 4. For Part A: Have relapsed or refractory solid or CNS tumors or have a diagnosis of DIPG or Diffuse Midline H3 K27M glioma. 5. For Part B: Patients must have a diagnosis of DIPG or Diffuse Midline H3 K27M glioma following treatment with radiation therapy; OR recurrent or refractory high grade glioma. 6. Have either measurable or evaluable disease for Part B of the study only. 7. 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. 8. Have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. 9. Myelosuppresive chemotherapy: Must not have received within 3 weeks of enrolment onto this study (6 weeks if prior nitrosourea). 10. Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. PEG-CGSF) 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. 11. Biologic (anti-neoplastic agent): At least 7 days after the last dose of 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. 12. Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody. 13. XRT: =/> 6 weeks since administration of radiation therapy; =/> 24 weeks must have elapsed if prior TBI. 14. MIBG therapy: At least 6 weeks must have elapsed since the completion of radio-labelled MIBG therapy. 15. Stem cell transplant or rescue, including autologous cell transplant: No evidence of active graft vs. host disease and =/> 12 weeks must have elapsed. 16. Haematological function as follows: • Absolute neutrophil count (ANC) =/> 1.0 x 109/L; • Platelet count =/> 50 x 109/L (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrolment); • Lymphocyte count =/> 0.5 x 109/L; • Haemoglobin =/> 80 g/L (may receive RBC transfusions); • Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x upper limit of normal (ULN). 17. Adequate Renal function defined as: • Creatine clearance or radioisotope GFR =/> 70ml/min/1.73 m2 or • A serum creatinine based on age/gender as follows: Age Maximum SerumCreatinine (?mol/L) Male Female 1 to < 2 years 52 52 2 to < 6 years 70 70 6 to < 10 years 88 88 10 to < 13 years 106 106 13 to < 16 years 132 124 =/> 16 years 150 124 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC 18. Adequate Liver function defined as: • Total bilirubin =/< 1.5 x ULN and • ALT =/< 5 x ULN (where ULN defined as 45 U/L) 19. Adequate cardiac function defined as: • Fractional shortening (FS) =/< 28% measured by echocardiography 20. Female patients • Female patients who are of NON-reproductive potential. (Pre-pubertal females, have undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy) o The parent or guardian of young female patients who have not yet started menstruation should verify that menstruation has not begun. If a young female patient reaches menarche during the study, then she is to be considered as a woman of childbearing potential from that time forward. or • Female patients of childbearing potential must have a negative serum pregnancy test upon study entry and must be willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration. o Highly effective methods of birth control include sexual abstinence, hormonal birth control, or intrauterine device (women), in combination with barrier methods. All study patients must be willing to ensure that corresponding sexual partners practice these same methods of highly effective birth control for the same duration. 21. Male patients • Male patients that are prepubertal on history and examination or • Male patients who are willing to use highly effective methods of birth control during the period of therapy and for 6 months following the last study drug administration. o Highly effective methods of birth control include sexual abstinence, vasectomy or a condom with spermicide in combination with barrier methods. All study patients must be willing to ensure that corresponding sexual partners practice these same methods of highly effective birth control for the same duration. Highly effective methods of birth control include sexual abstinence, hormonal birth control, or intrauterine device (women), vasectomy or a condom with spermicide (men) in combination with barrier methods. All study patients must be willing to ensure that corresponding sexual partners practice these same methods of highly effective birth control for the same duration.
Exclusion criteria
1. Pregnant or breast-feeding women. 2. Any active uncontrolled infection. 3. Disease of any major organ system that would compromise their ability to withstand therapy. 4. Pre-existing allergy to ACT001 or related compounds. 5. History of infection with HIV or hepatitis B or C viruses. 6. Concurrent or prior (within 7 days of enrolment) anticoagulant therapy, except low molecular weight heparins or low dose aspirin. 7. Patients currently receiving another investigational drug. 8. Patients currently receiving other antineoplastic agents 9. All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the Investigator. 10. Will not be available for protocol-required study visits or procedures, to the best of the patient/parent/guardian’s and investigator’s knowledge. 11. Any kind of disorder that, in the opinion of the investigator, may compromise the ability of the patient/parent/guardian to give written informed consent and/or to comply with all required study procedures. 12. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to patient safety or interfere with the study evaluation, procedures or completion.
Outcome results
None listed