Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Chondrosarcoma

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Ivosidenib

Enzyme Inhibitors

Participants will have locally advanced/metastatic or recurrent operable chondrosarcoma

AG-120 500 mg orally once daily days 1-28 of a 28-day cycle

AG-120

Ciara M Kelly, MBBCh, BAO

William D Tap, MD

Nara Sobreira, MD

Juan Manuel Schvartzman, MD, PhD

Gabriel Tinoco, MD

Anthony Conley, MD

This study is being done to see whether AG-120 is an effective and safe treatment for people with advanced/metastatic or recurrent chondrosarcoma that has IDH1 mutation.

AG-120 in People With IDH1 Mutant Chondrosarcoma

Phase II Study of AG-120 in IDH1 Mutant Chondrosarcoma

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Progression free survival includes both disease progression (as defined by RECIST 1.1) and death from any cause

Agios Pharmaceuticals, Inc.

Memorial Sloan Kettering Cancer Center

Nervous System Diseases

Musculoskeletal Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Neuroendocrine

Neuroblastoma

Esthesioneuroblastoma, Olfactory

Skull Base Neoplasms

Maxillary Sinus Neoplasms

Neoplasms, Glandular and Epithelial

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumors

Skull Neoplasms

Bone Neoplasms

Bone Diseases

Olfactory Nerve Diseases

Cranial Nerve Diseases

Paranasal Sinus Neoplasms

Nose Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nose Diseases

Respiratory Tract Diseases

Paranasal Sinus Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Olfactory Neuroblastoma

Sinonasal Undifferentiated Carcinoma

Neuroepithelioma

Neuroendocrine Tumor

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

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

Enasidenib

NCI Medical Oncology Referral Office

Charalampos Floudas, M.D.

National Cancer Institute Referral Office

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....

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.

Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors

Phase II Study of Enasidenib in IDH2-mutated Malignant Sinonasal and Skull Base Tumors

.All collected IPD will be shared. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.@@@@@@

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

Adverse events assessed per CTCAE version 5

Fraction of participants experiencing CBR = CR+PR+ SD \> 16 weeks

The date of first treatment until date of death or last follow-up

Descriptive statistics of AE occurence per UGTIA1 genotype

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AG-120 in People With IDH1 Mutant Chondrosarcoma	NCT04278781	Chondrosarcoma Chondrosarcoma,... Chondrosarcoma,... IDH1 Gene Mutat...	AG-120	18 Years -	Memorial Sloan Kettering Cancer Center
Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors	NCT06176989	Metastatic Chon... Locally Advance... Metastatic Sino... Locally Advance... Metastatic Larg... Locally Advance... Metastatic Olfa... Locally Advance... Metastatic Sino... Locally Advance...	Enasidenib	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors	NCT06176989	Metastatic Chon... Locally Advance... Metastatic Sino... Locally Advance... Metastatic Larg... Locally Advance... Metastatic Olfa... Locally Advance... Metastatic Sino... Locally Advance...	Enasidenib	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
AG-120 in People With IDH1 Mutant Chondrosarcoma	NCT04278781	Chondrosarcoma Chondrosarcoma,... Chondrosarcoma,... IDH1 Gene Mutat...	AG-120	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for locally advanced chondrosarcoma