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Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors

ConditionsAnatomic Stage IV Breast Cancer AJCC v8Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Locally Advanced Malignant Solid NeoplasmLocally Advanced MelanomaLocally Advanced Primary Malignant Central Nervous System NeoplasmLocally Advanced SarcomaMetastatic Malignant Solid NeoplasmMetastatic MelanomaMetastatic Primary Malignant Central Nervous System NeoplasmMetastatic SarcomaPathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Prognostic Stage IIIC Breast Cancer AJCC v8Prognostic Stage IV Breast Cancer AJCC v8Stage IIIC Colorectal Cancer AJCC v8Stage IIIC Lung Cancer AJCC v8Stage IV Colorectal Cancer AJCC v8Stage IV Lung Cancer AJCC v8Stage IVA Colorectal Cancer AJCC v8Stage IVA Lung Cancer AJCC v8Stage IVB Colorectal Cancer AJCC v8Stage IVB Lung Cancer AJCC v8Stage IVC Colorectal Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorM.D. Anderson Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Avapritinib

    Drug

    Given PO

Treatment groups

50 Participants
are divided into 1 treatment group
Group A: Treatment (avapritinib)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
or date of death from any cause, whichever came first, assessed up to 50 months

Secondary outcomes

1

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)
2

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
3

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)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

M.D. Anderson Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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