This phase II trial studies the effect of avapritinib in treating malignant solid tumors that have a genetic change (mutation) in CKIT or PDGFRA and have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Avapritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Avapritinib may help to control the growth of malignant solid tumors.
PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) of avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO criteria (as appropriate). SECONDARY OBJECTIVES: I. To evaluate the duration of response (DoR) to avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors. II. To evaluate the disease control rate (DCR) of avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors. III. To determine the safety and tolerability of avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors, as assessed by the National Cancer institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. EXPLORATORY OBJECTIVES: I. To evaluate the overall survival (OS) of patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors receiving avapritinib. II. To evaluate the ORR and DoR of avapritinib in patients with measurable brain or central nervous system (CNS) metastases at baseline. III. To evaluate the progression-free survival (PFS) of patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors receiving avapritinib. IV. To evaluate the correlation between genomic mutations and clinical outcome. V. To evaluate time on treatment (including patients treated beyond progression). VI. To evaluate baseline genomics and circulating cell-free deoxyribonucleic acid (cfDNA) and functional analyses of variants. OUTLINE: Patients receive avapritinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 8 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Given PO
M D Anderson Cancer Center
Houston, Texas, United States
RECRUITINGOverall response rate (ORR)
ORR defined as confirmed complete response (CR) or partial response (PR) from the time of study treatment initiation until disease progression as centrally assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria, as appropriate. Confirmed CR or PR will be defined as a repeat assessment performed 4 weeks (+/-3 days) after the criteria for response is first met. Will estimate ORR along with 90% confidence interval according to Clopper-Pearson method for each cohort and for specific tumor type.
Time frame: or date of death from any cause, whichever came first, assessed up to 50 months
Duration of response (DoR)
Determined for patients with best overall response of confirmed CR or PR (centrally assessed); DoR is defined as the number of months from the start of CR or PR (whichever response is recorded first) and subsequently confirmed to the first date of documented PD or death. Descriptive statistics will be used.
Time frame: Up to study completion (estimated 4 years)
Disease control rate (DCR)
DCR defined as BOR of confirmed CR or PR (either of any duration) or stable disease SD \>= 16 weeks following study treatment initiation. Descriptive statistics will be used.
Time frame: >= 16 weeks following study treatment initiation
Incidence of adverse events
Will be measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive statistics will be used.
Time frame: Up to study completion (estimated 4 years)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.