This phase I/II trial tests the safety, side effects, best dose and how well giving daraxonrasib works for the treatment of pediatric patients with solid tumors with RAS mutations that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Daraxonrasib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving daraxonrasib may be safe, tolerable and/or effective in treating patients with relapsed or refractory solid tumors with RAS mutations.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
PARTS A1 AND B: Patients must be ≥ 2 years and ≤ 17 years of age at the time of study enrollment
PART A2: Patients must be ≥ 1 year and ≤ 17 years of age at the time of study enrollment
Patients with recurrent or refractory extracranial solid tumors. Patients must have had histologic verification of malignancy at original diagnosis or relapse
PARTS A1 AND A2: Patients with relapsed or refractory RAS mutant extracranial solid tumors
Disqualifiers
Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study and for at least one month after the last dose of study treatment for females and one week after the last dose of study treatment for males. Abstinence is an acceptable method of birth control
Corticosteroids: Patients must be on a stable or decreasing dose of corticosteroids for at least 7 days prior to enrollment. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
Anti-GVHD agents post-transplant: Patients must not be receiving tacrolimus or other medications to prevent graft-versus-host disease post bone marrow transplant
Trial design
Design model
Single group
Treatments tested in this trial
Biospecimen Collection
Procedure/Surgery
Undergo blood and urine sample collection
Bone Marrow Aspiration
Procedure/Surgery
Undergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/Surgery
Undergo bone marrow biopsy
Daraxonrasib
Drug
Given PO
Diagnostic Imaging Testing
Procedure/Surgery
Undergo diagnostic imaging
X-Ray Imaging
Procedure/Surgery
Undergo x-ray imaging
Treatment groups
77 Participants
are divided into 1 treatment group
Group A: Treatment (daraxonrasib)Experimental treatment 6 interventions
Trial outcomes
Primary outcomes
1
Maximum tolerated dose (MTD) (Phase 1 part A)
MTD defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity during cycle 1 of therapy.
Time frame
Up to completion of cycle 1 (cycle length = 21 days)
2
Incidence of adverse events (Phase 1 and 2, parts A and B)
Toxicities for patients will be described separately. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
Time frame
Up to 5 years
3
Best response of disease (Phase 2 dose expansion [part B])
Disease response will be assessed according to Response Evaluation Criteira in Solid Tumors (RECIST) criteria for patients with solid tumors (International Neuroblastoma Response Criteria \[INRC\] for patients with neuroblastoma), and will be reported descriptively.
Time frame
Up to 5 years
Secondary outcomes
1
Best response of disease (Phase 1, part A)
Disease response will be assessed according to RECIST criteria for patients with solid tumors (INRC for patients with neuroblastoma), and will be reported descriptively.
Time frame
Up to 5 years
2
Best response of disease (Phase 1, part B)
Disease response will be assessed according to RECIST criteria for patients with solid tumors (INRC for patients with neuroblastoma), and will be reported descriptively. For part B1 (rhabodomyosarcoma) response rate will be estimated by the uniform minimum variance unbiased estimate with one-sided 95% confidence intervals. For part B2 (neuroblastoma) and B3 (other) response rates will be estimated as the proportion of patients who are responders with one-sided exact 93% confidence intervals.
Time frame
Up to 5 years
3
Pharmacokinetics (Phase 1 dose escalation and phase 2 dose expansion [parts A and B])
A descriptive analysis of pharmacokinetic (PK) parameters of daraxonrasib will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Time frame
At cycle 1 day 1 (predose, 30 minutes, 2 hours, 4.5 hours, 7 hours post dose), cycle 1 day 15 predose, cycle 2 day 1 (cycle length = 21 days)
4
Progression free survival
Time frame
Up to 5 years
Other outcomes
1
Frequency of detectable RAS mutations by circulating tumor deoxyribonucleic acid (ctDNA)
Time frame
At cycle 1 day 1 (pre-dose), cycle 1 day 8, cycle 2 day 1, cycle 2 days 21 and end of treatment (cycle length = 21 days)
2
Mutant allele fraction in ctDNA
Time frame
At cycle 1 day 1 (pre-dose), cycle 1 day 8, cycle 2 day 1, cycle 2 days 21 and end of treatment (cycle length = 21 days)
Locations
This trial has no locations.
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
