Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT04771520
Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors
A Phase 2 study testing Avapritinib in people with Anatomic Stage IV Breast Cancer AJCC v8 and Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
- What is being tested?
- Avapritinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jan 2021to 31 Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient (or legally acceptable representative if applicable) provides written informed consent for the study.
- Male or female ≥18 years of age on the day of informed consent signing. Adolescent patients aged 12 years and older are allowed with signed assent and parental consent according to institutional guidelines and requirements.
- Cohorts 1 and 2: Patient has a locally advanced or metastatic solid tumor and has progressed on appropriate standard therapy, has not shown clinically meaningful benefit to appropriate standard therapy, has no available standard therapy, or has declined appropriate standard therapy.
- NOTE: Specific solid tumor types include but are not limited to melanoma, breast cancer, lung cancer, gastroesophageal cancer, colorectal cancer, sarcoma, solid tumors NOS, and primary CNS tumors. Patients with any other recurrent solid tumor type with the exception of gastrointestinal stromal tumor (GIST) will be eligible.
- Cohort 3: Patient has newly diagnosed IDH wild-type, MGMT-unmethylated glioblastoma. Patients must have received prior treatment with radiation and concurrent temozolomide per standard of care.27 Patients must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.
- Measurable disease per the RECIST v1.1 or RANO criteria, as appropriate, for Cohorts 1 and 2. Patients in Cohort 3 can have measurable or non-measurable disease per the RANO criteria.
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- 6 Documented pathogenic CKIT activating mutation (Cohort 1) OR pathogenic PDGFRA activating mutation (Cohort 2) based on Clinical Laboratory Improvement Amendments-certified next-generation sequencing diagnostic test. Cohort 3 should have pathogenic CKIT or PDGFRA activating mutation/amplification based on CLIA-certified NGS diagnostic test. CKIT and PDGFRA mutation pathogenicity will be verified by the MD Anderson Cancer Center's Precision Oncology Decision Support team. Acceptable CKIT/PDGFRA mutations for study eligibility are listed in Appendix E.
- 7. Has available archival tissue for CKIT/PDGFRA mutation (amplification [Cohort 3 only]) retrospective testing.
- 8. Adequate organ and marrow function as defined below within 7 days of study treatment initiation:
- White blood cell count >2,500/µL and <15,000/µL
- Absolute neutrophil count ≥1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
- Platelet count ≥75 × 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility)
- Hemoglobin ≥9.0 g/dL (without blood transfusion within 7 days of laboratory test used to determine eligibility)
- Total bilirubin ≤1.5 × upper limit of normal (ULN); if hepatic metastases are present, ≤3.0 × ULN
- Aspartate transaminase and alanine transaminase ≤2.5 × ULN; if hepatic metastases are present, ≤5.0 × ULN
- Serum creatinine ≤2.0 × ULN or creatinine clearance ≥45 mL/min. 9. Cardiac ejection fraction >45% per screening echocardiogram or multigated acquisition scan.
- 10. Eastern Cooperative Oncology Group performance status of 0-2.
- 11. Life expectancy ≥3 months.
- 12. Willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.
- 13. Willing to undergo biopsy as required by the study.
- 14. Females must be postmenopausal (defined as ≥45 years of age with at least 12 months of spontaneous amenorrhea) or premenopausal with documented surgical sterilization (tubal ligation, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or evidence of non-childbearing status for women of childbearing potential (negative serum beta-human chorionic gonadotropin pregnancy test) within 3 days of study treatment initiation.
- 15. Females of childbearing potential must either abstain from heterosexual intercourse or use a highly effective method of contraception for the course of the study and for 6 weeks after the last dose of study treatment.
- 16. Males with female partners of reproductive potential must either abstain from sexual intercourse or they and their partners must use a highly effective method of contraception when engaging in sexual intercourse for the course of the study through 30 days after the last dose of study treatment.
Who cannot join
- Patients eligible for this study must not meet any of the following criteria:
- Patients who have GIST.
- Patients with tyrosine kinase inhibitor-resistant CKIT mutation V654A or T670I.
- Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose or increasing dose of systemic corticosteroids) and without imminent need of radiation therapy) are eligible (including those with untreated brain metastases). If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and/or complications prior to eligibility assessment. For patients who have received prior radiation therapy, post-treatment magnetic resonance imaging scan should show no increase in brain lesion size/volume.
- History of documented congestive heart failure (New York Heart Association functional classification III-IV) or serious cardiac arrhythmias requiring treatment.
- QT interval corrected using Fridericia's formula of >470 msec.
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- Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to study treatment initiation.
- Prior anticancer chemotherapy, hormone therapy, immunotherapy, targeted therapy, radiation therapy, or surgery within 2 weeks prior to study treatment initiation.
- NOTE: Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline (except alopecia). Patients with ≤ Grade 2 neuropathy are eligible.
- NOTE: If patient received major surgery, she/he must have recovered adequately from the toxicity and/or complications from the intervention prior to study treatment initiation.
- NOTE: Patients in Cohort 3 must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.
- Symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
- History of psychotic or depressive disorder. Patients whose disorder is well controlled on a stable antipsychotic or antidepressant medication for at least 12 months prior to study entry will be eligible.
- Concomitant use of a known strong cytochrome P450 (CYP)3A4 inhibitor or strong CYP3A4 inducer. The required washout period prior to study treatment initiation is 2 weeks or 5 half-lives, whichever is shortest.
- Females who are pregnant or breastfeeding.
- Unable to swallow and retain oral medications.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Known additional malignancy that is progressing or requires active treatment. NOTE: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the investigator.
- Prior treatment with an intracerebral agent or bevacizumab (Cohort 3 only).
- Prior treatment including radiation, chemotherapy, or immunotherapy for low-grade glioma (Cohort 3 only).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Jordi Rodon Ahnert, 713-563-1930, jrodon@mdanderson.org
Jordi Rodon Ahnert
About this study
Official title: Phase 2 Study of Avapritinib in Patients With CKIT or PDGFRA Mutation-Positive Malignant Solid Tumors
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8, Locally Advanced Malignant Solid Neoplasm, Locally Advanced Melanoma
- Being tested
- Avapritinib
- Medical subject headings
- Neoplasm Metastasis, Melanoma, Sarcoma, Colorectal Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvapritinibDrug
Also called (S)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1Hpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-yl)pyrimidin-5-yl)ethan-1-amine, AYVAKIT, BLU-285, CS3007
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (avapritinib) | Experimental | Patients receive avapritinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Avapritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall 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.
Measured: or date of death from any cause, whichever came first, assessed up to 50 months
Secondary outcomes (3)
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.
Measured: 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.
Measured: >= 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.
Measured: Up to study completion (estimated 4 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start20 Jan 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jordi Rodon Ahnert, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04771520
- Sponsor's protocol ID
- 2020-0439
- Other IDs
- NCI-2021-00702, 2020-0439
- Status last verified
- Jun 2026
- First submitted
- 8 Feb 2021
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No