Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors

Recruiting now · Phase 2

Conditions studied: Metastatic Chondrosarcoma, Locally Advanced Chondrosarcoma, Metastatic Sinonasal Adenocarcinoma, Locally Advanced Sinonasal Adenocarcinoma, Metastatic Large-cell Neuroendocrine Carcinoma, Locally Advanced Large-cell Neuroendocrine Carcinoma, Metastatic Olfactory Neuroblastoma, Locally Advanced Olfactory Neuroblastoma, Metastatic Sinonasal Undifferentiated Carcinoma, Locally Advanced Sinonasal Undifferentiated Carcinoma

In brief

Background: Cancers of the nasal cavity or skull base are rare. They often are not diagnosed until they are at an advanced stage, and they often spread to other parts of the body. These cancers may have mutations in a gene called IDH2. Researchers want to find out if a drug (enasidenib) that targets the IDH2 mutation can help people with these cancers. Objective: To test enasidenib in people with cancers of the nasal cavity or skull base. Eligibility: People aged 18 years and older with rare cancers of the nasal cavity or the base of the skull. Their cancer must have an IDH2 gene mutation, and it must have recurred locally or spread to other parts of the body. These cancers can include sinonasal undifferentiated carcinoma; olfactory neuroblastoma; sinonasal large-cell neuroendocrine carcinoma; poorly differentiated sinonasal adenocarcinoma; or chondrosarcoma. Design: Participants will be screened. They will have a physical exam with blood and urine tests and tests of their heart function. They will have imaging scans of their brain, skull base, neck, chest, abdomen, and pelvis. A sample of tumor tissue will be collected. Enasidenib is a tablet taken by mouth with a glass of water. Participants will take the drug once a day, every day, in 28-day cycles. They will not have resting periods between cycles. Participants will visit the clinic on the first day of each cycle to receive the tablets they will need to take at home until the beginning of the next cycle. They will keep a diary to record the time of each dose they take. Participants may remain in the study as long as the drug is helping them....

Key facts

Study ID: NCT06176989
Run by: National Cancer Institute (NCI)
People needed: 40
Starts: 2024-03-04
Expected to finish: 2030-12-31
Last updated by the study team: 2026-06-03

Who can join

Age: 18 and older, up to 120. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Prior treatment with IDH1/2 inhibitor.
Use of other investigational agents within 3 weeks or 5 half-lives prior to first treatment administration.
Systemic anticancer treatment within 3 weeks prior to first treatment administration. All residual treatment-related toxicities must have resolved or be minimal and not constitute a safety risk. Note: Bisphosphonates and denosumab are permitted medications.
Large-field radiotherapy within 4 weeks prior to first treatment administration. All residual treatment-related toxicities must have resolved (except xerostomia) or be minimal and not constitute a safety risk.
Major surgery within 2 weeks prior to first treatment administration. If participant underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. Minimally invasive procedures are permitted.
Participants with new or progressive (active) brain metastases or leptomeningeal disease.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to enasidenib.
Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to first treatment administration.
Participants taking the following sensitive cytochrome P450 (CYP) substrate medications that have a narrow therapeutic range are excluded from the study unless they can be transferred to other medications prior to enrolling: warfarin, phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline and tizanidine (CYP1A2). Excluded medications should not be given within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study medication. Other CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 substrates may be given concurrently if medically necessary.
Participants taking sensitive substrates of P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), OAT1, OATP1B1, OATP1B3, and OCT2 should be excluded from the study unless the substrate medication can be dose modified according to the package insert of the substrate (if applicable) and adverse events can be closely monitored during concurrent administration. Alternately, participants can be transferred to other medications prior to enrolling. Excluded medications should not be given within 3 weeks or 5 half-lives (whichever is shorter) prior to the first of study medication.
Participants taking medications that are known to prolong the QT interval unless the participant can be transferred to other medications at least 5 half-lives prior to the start of the study treatment. If equivalent medication is not available, QTc will be closely monitored
Impaired cardiovascular function or clinically significant cardiovascular disease, including, but not limited to, any of the following:
cerebral vascular accident/stroke (< 3 months prior to enrollment),
uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg)
acute coronary syndromes (including myocardial infarction < 6 months prior to enrollment, unstable angina),
Symptomatic congestive heart failure
Rate-corrected QT (QTc using Fridericia formula [QTcF]) >450 msec
Severe/uncontrolled ventricular arrhythmia
Known short-gut syndrome, gastroparesis, or other conditions that limit the ingestion of gastrointestinal absorption of drugs administered orally.
Active infection requiring treatment with parenteral antibiotics.
History of second malignancy within 3 years prior to enrollment except for the following: adequately treated localized basal cell or squamous skin cancer, cervical carcinoma in situ, superficial bladder cancer, other localized malignancy which has been adequately treated or malignancy which does not require active systemic treatment (e.g., low risk CLL).
Participant pregnancy
Uncontrolled intercurrent illness (including psychiatric) or social situations, that may limit interpretation of results or increase risk to the participant:

Where it is running

National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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