Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors

NCT06176989 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001552001552-C
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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....

Conditions

Locally Advanced Chondrosarcoma; Metastatic Sinonasal Adenocarcinoma; Metastatic Chondrosarcoma; 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

Keywords

R140 mutation; R172 mutation; Small Molecule Inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) in all study participants

  The date of first treatment until the date of disease progression or death without progression

  up to 5 years post study treatment

Secondary Outcomes (8)

• safety

  from study treatment initiation up to 28 days post study treatment

• clinical benefit rate (CBR: CR+PR+SD>4 months) in participants with IDH2m SNUC

  up to 5 years post study treatment

• PFS in non-SNUC IDH2m tumors

  up to 5 years post study treatment

• Overall survival (OS) in non-SNUC IDH2m tumors

  up to 5 years post study treatment

• clinical benefit rate (CBR: CR+PR+SD>4 months) in participants with non-SNUC IDH2m tumors

  up to 5 years post study treatment

Study Arms (1)

1

EXPERIMENTAL

Participants with IDH2 mutated (R140/R172) malignant sinonasal and skull base tumors.

Drug: Enasidenib

Interventions

Enasidenib DRUG

100mg PO (orally) once daily, on days 1-28 of a 28-day cycle

1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed locally advanced or metastatic SNUC, ONB, LCNEC, SNAC, and CS with documented somatic (tumor) IDH2 mutations R140 or R172. Primary tumors must be located in the sinonasal cavity and/or skull base.
• Locally advanced disease must not be amenable to potentially curative surgery/radiotherapy.
• Must have recurred or progressed following prior systemic therapy administered in the recurrent or metastatic setting. Any number of prior systemic therapies is allowed.
• Measurable disease, per RECIST 1.1. Lesions in a previously irradiated field are considered measurable if they have been demonstrated as progressing during or following radiotherapy.
• Age \>=18 years.
• ECOG performance status 0-2
• Adequate organ and marrow function as defined below:
• hemoglobin \>=9 g/dL (PRBC transfusion allowed)
• absolute neutrophil count (ANC) \>=1,000/mcL
• platelets \>=75,000/mcL
• total bilirubin \<= 1.5 x institutional upper limit of normal (iULN) (\<=3x in the presence of Gilbert s syndrome or a UGT1A1 gene mutation)
• AST/ALT \<=1.5 x iULN (\<=2.5 x iULN if liver metastasis)
• Serum Creatinine \<=1.5 x iULN OR
• Creatinine Clearance \>=40 mL/min by Cockroft-Gault GFR estimation for subjects with serum creatinine levels \<=1.5 X iULN
• Participants with treated brain or central nervous system metastases are eligible if follow-up brain imaging after at least 4 weeks following CNS-directed therapy shows no evidence of progression.

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),

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Chondrosarcoma; Esthesioneuroblastoma, Olfactory; Sinonasal undifferentiated carcinoma

Interventions

enasidenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neuroblastoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Olfactory Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases

Study Officials

• Charalampos Floudas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Medical Oncology Referral Office

CONTACT

(240) 760-6050; ncimo_referrals@nih.gov

Charalampos Floudas, M.D.

CONTACT

(240) 474-1575; charalampos.floudas@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: December 20, 2023
• Study Start: March 4, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 28, 2026

Record last verified: 2026-04-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing. This study will comply with the NIH Genomic Data Sharing (GDS) Policy, which applies to all new and ongoing NIH IRP-funded research, as of January 25, 2015, that generates large-scale human or non-human genomic data, as well as the use of these data for subsequent research. Large-scale data include genome-wide association studies (GWAS), single nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data. Therefore, unlinked genomic data will be deposited in public genomic databases such as dbGaP in compliance with the NIH Genomic Data Sharing Policy.@@@@@@@@@@@@
• Access Criteria: Data from this study may be requested by contacting the PI. Genomic data are made available via dbGaP through requests to the data custodians.@@@@@@

Locations

US (1)