Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors
- Conditions
- Locally Advanced ChondrosarcomaLocally Advanced Sinonasal AdenocarcinomaMetastatic Olfactory NeuroblastomaLocally Advanced Olfactory NeuroblastomaMetastatic Sinonasal Undifferentiated CarcinomaMetastatic Sinonasal AdenocarcinomaLocally Advanced Large-cell Neuroendocrine CarcinomaMetastatic ChondrosarcomaLocally Advanced Sinonasal Undifferentiated CarcinomaMetastatic Large-cell Neuroendocrine Carcinoma
- Interventions
- Registration Number
- NCT06176989
- Lead Sponsor
- National Cancer Institute (NCI)
- 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....
- Detailed Description
Background:
* Sinonasal undifferentiated carcinoma (SNUC) and olfactory neuroblastoma (ONB) are rare malignant sinonasal and skull base tumors, a group that also includes sinonasal adenocarcinoma, squamous cell carcinoma, large cell neuroendocrine carcinoma, sinonasal papilloma, chondrosarcoma (CS), chordoma and others.
* These malignancies are often diagnosed at a locally advanced stage. They tend to invade locally and have high rates of regional spread to the neck, and distally to the lungs and bones. For early locoregional disease multimodality treatment is used: surgery with postoperative radiotherapy, with or without induction chemotherapy. Treatment approaches for metastatic disease are largely based on institutional case series and consist largely of systemic chemotherapy.
* Recent genomic studies have reported isocitrate dehydrogenase-2 (IDH2) hotspot mutations in up to 87% of SNUC, 17% of ONB, and in 12% of chondrosarcomas; it has also been reported in sinonasal large-cell neuroendocrine carcinoma (LCNEC) and poorly differentiated sinonasal adenocarcinoma (SNAC).
* IDH2 hotspot mutations have been identified in acute myeloid leukemia, glioblastoma, myelodysplastic syndromes, and cholangiocarcinoma.
* Enasidenib is an orally bioavailable, selective and potent inhibitor of mutated IDH2, which is approved in relapsed IDH2 mutated (IDH2m) AML.
* Inhibition of mutated IDH2 may be clinically useful in IDH2m malignant sinonasal and skull base tumors.
Objectives:
- To estimate the overall progression free survival (PFS) based on treatment with enasidenib in all study participants with IDH2m malignant sinonasal and skull base tumors.
Eligibility:
* Histologically or cytologically confirmed locally advanced or metastatic SNUC, ONB, LCNEC, SNAC, and CS with documented somatic (tumor) IDH2 mutations R140 or R172.
* Eligible primary tumor locations are sinonasal cavity and 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
* Age \>= 18 years
* ECOG Performance Status 0-2
* Adequate organ function
Design:
* Single-arm Phase II trial to determine PFS in participants with recurrent or metastatic IDH2m malignant sinonasal and skull base tumors.
* Enasidenib will be given at a dose of 100mg orally once daily until progressive disease or unacceptable toxicity.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Enasidenib Participants with IDH2 mutated (R140/R172) malignant sinonasal and skull base tumors.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) in all study participants up to 5 years post study treatment The date of first treatment until the date of disease progression or death without progression
- Secondary Outcome Measures
Name Time Method safety from study treatment initiation up to 28 days post study treatment Adverse events assessed per CTCAE version 5
clinical benefit rate (CBR: CR+PR+SD>4 months) in participants with IDH2m SNUC up to 5 years post study treatment Fraction of participants experiencing CBR = CR+PR+ SD \> 16 weeks
PFS in non-SNUC IDH2m tumors up to 5 years post study treatment The date of first treatment until the date of disease progression or death without progression
Overall survival (OS) in non-SNUC IDH2m tumors up to 5 years post study treatment The date of first treatment until date of death or last follow-up
clinical benefit rate (CBR: CR+PR+SD>4 months) in participants with non-SNUC IDH2m tumors up to 5 years post study treatment Fraction of participants experiencing CBR = CR+PR+ SD \> 16 weeks
Overall survival (OS) in participants with IDH2m SNUC up to 5 years post study treatment The date of first treatment until date of death or last follow-up
PFS in participants with IDH2m SNUC up to 5 years post study treatment The date of first treatment until the date of disease progression or death without progression
Correlate UGTIA1 genotypes with toxicity from study treatment initiation up to 28 days post study treatment Descriptive statistics of AE occurence per UGTIA1 genotype
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States