Clinical Trials /

AG-120 in People With IDH1 Mutant Chondrosarcoma

NCT04278781

Description:

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.

Related Conditions:
  • Chondrosarcoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AG-120 in People With IDH1 Mutant Chondrosarcoma
  • Official Title: Phase II Study of AG-120 in IDH1 Mutant Chondrosarcoma

Clinical Trial IDs

  • ORG STUDY ID: 19-393
  • NCT ID: NCT04278781

Conditions

  • Chondrosarcoma
  • Chondrosarcoma, Grade 2
  • Chondrosarcoma, Grade 3
  • IDH1 Gene Mutation

Interventions

DrugSynonymsArms
AG-120Chondrosarcoma

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ChondrosarcomaExperimentalParticipants will have locally advanced/metastatic or recurrent operable chondrosarcoma
  • AG-120

Eligibility Criteria

        Inclusion Criteria:

          -  Be >/= 18 years of age

          -  Have a histological diagnosis (fresh or archived tumor biopsy sample) of locally
             advanced/metastatic or recurrent operable chondrosarcoma (conventional grade 2 or 3
             only) confirmed by central pathology review

               -  Patients with low grade (grade 1) and dedifferentiated chondrosarcoma are
                  ineligible

               -  Patients with biopsy proven low grade (grade 1) pelvic chondrosarcoma are
                  ineligible unless they have radiological imaging consistent with higher grade
                  disease in which case they will be deemed potentially eligible. In such cases the
                  pre-treatment biopsy should be taken where feasible from the area of presumed
                  higher-grade disease to confirm grade 2 or 3 disease to confirm eligibility

               -  Patients without confirmation of grade 2 or 3 disease will not be eligible for
                  the study unless in the case where radiology features are consistent with high
                  grade disease but a biopsy confirmation of this is not technically feasible. Such
                  cases should be discussed with the principal investigator before enrollment onto
                  the study

          -  Have a documented IDH1 gene mutation (from a fresh tumor biopsy or the most recent
             archived tumor tissue available) confirmed by a CLIA approved laboratory.

          -  Have an ECOG OS score of 0 to 2.

          -  Have expected survival of >/= 4 months.

          -  Have at least one measurable lesion as defined by RECIST 1.1, subjected who have
             received prior local therapy are eligible provided the measurable disease falls
             outside of the treatment field or within the field and has shown >/=20% growth in size
             since post-treatment assessment.

          -  Have documented radiographic disease progression within the preceding 4 months before
             study entry (date ICF signed).

        Have recovered from toxicities associated with prior anti-cancer therapy to baseline unless
        stabilized under medical management (see washout time from different therapies in Exclusion
        Criteria section).

          -  Have adequate bone marrow functions as evidenced by:

               -  Absolute neutrophil count >/=1,500/mm^3 or 100 x 10^9/L.

               -  Hemoglobin >/=8/dL.

               -  Platelets >/=100,000/mm^3 or 100 x 10^9/L.

          -  Have adequate hepatic function as evidenced by:

               -  Serum total bilirubin </=2 x upper limit of normal (ULN), unless considered due
                  to Gilbert's disease.

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </=5 x ULN.

          -  Have adequate renal function as evidenced by:

               -  Serum creatinine <1.5 x ULN OR

               -  creatinine clearance >/= 50ml/min based on the cockcroft-gault glomerular
                  filtration rate (GFR) estimation:

               -  (140 Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine

          -  Be able to understand and willing to sign the informed consent form and to comply with
             scheduled visits, treatment plans, procedures and laboratory tests, including serial
             peripheral blood sampling and urine sampling, during the study. A legally authorized
             representative may consent on behalf of a subject who is otherwise unable to provide
             informed consent if acceptable to and approved by the site's Institutional Review
             Board (IRB)

          -  Be able to swallow oral medication.

          -  Female subjects with reproductive potential must have a negative serum pregnancy test
             prior to the start of therapy, or a confirmation from an obstetrician in case of
             equivocal serum pregnancy results. Females of reproductive potential are defined as
             sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy,
             or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not
             menstruated) for at least 24 consecutive months (i.e., have not had menses at any time
             in the preceding 24 consecutive months). Women of reproductive potential, as well as
             fertile men and their partners who are female with reproductive potential, must agree
             to use 2 effective forms of contraception (including at least 1 barrier form) from the
             time of giving informed consent throughout the study and for 90 days (both females and
             males) following the last dose of study drug. Effective forms of contraception are
             defined as hormonal oral contraceptive, injectables, patches, intrauterine devices,
             intrauterine hormone-releasing systems bilateral tubal ligation, condoms with
             spermicide, or male partner sterilization.

        Exclusion Criteria:

          -  Received a prior IDH1 inhibitor.

          -  Received systemic anticancer therapy or an investigational agent < 3 week prior to the
             Day 1 (washout from prior immune based anticancer therapy is 4 weeks).

          -  Received radiotherapy or other local intervention to metastatic sites of disease <2
             weeks prior to Day 1.

          -  Underwent major surgery within 4 weeks of Day 1 or have not recovered from clinically
             significant post-surgery toxicities.

          -  Have known symptomatic brain metastasis requiring steroids. Subject with previously
             diagnosed brain metastases are eligible if they completed their treatment and have
             recovered from the acute effects of radiation therapy or surgery prior to study entry,
             have discontinued corticosteroid treatment for these metastases for at least 4 weeks
             and have a radiographically stable disease for a least 3 months prior to study entry.

             *Note: up to 10mg per day of prednisolone or equivalent will be allowed,

          -  Has another concurrent active cancer requiring therapeutic intervention.

          -  Are pregnant or breastfeeding.

          -  Are taking known strong CYP3A4 inducers or sensitive CYP3A4 substrate medications with
             a narrow therapeutic window unless they can be transferred to other medication within
             >/=5 half-lives prior to dosing

          -  Are taking p-glycoprotein (P-gp) transporter-sensitive substrate medications with a
             narrow therapeutic window, unless they can be transferred to other medications within
             >/= half-lives prior to dosing, or unless the medications can be properly monitored
             during the study.

          -  Have an active infection requiring systemic anti-infective therapy or with an
             unexplained fever > 38.5 degrees C within 7 days of Day 1 (at the discretion of the
             investigator, subjects with tumor fever may be enrolled).

          -  Have any known hypersensitivity to any components of AG-120.

          -  Have significant active cardiac disease within 6 months prior to the start of study
             treatment, including New York Heart Association Class II or IV congestive heart
             failure: myocardial infraction: unstable angina; and/or stroke.

          -  Have LVEP <40% by ECHO and/or MUGA scan obtained within 28 days prior to the start of
             the study treatment.

          -  Have a heart-rate corrected QT interval [using Frederica's Formula] (QTcF) >/=450msec
             or other factor that increase the risk of QT prolongation or arrhythmic events (e.g.,
             heart failure, hypokalemia, family history of long QT interval syndrome). Bundle
             branch block and prolonged QTcF interval are permitted with approval of the principal
             investigator.

          -  Are taking medications known to prolong the QT interval, unless they can have
             transferred to other medications within >/= half-lives prior to dosing, or unless the
             medications can be properly monitored during the study (If equivalent medication is
             not available, QTcF should be closely monitored).

          -  Have known active hepatitis B (HBV) or hepatitis C (HCV) infections, known positive
             human immunodeficiency virus (HIV) antibody results, or acquired immunodeficiency
             syndrome (AIDS) related illness, Subjects with a sustained viral response to HCV or
             immunity to prior HBV infection will be permitted. Subjects with chronic HBV that is
             adequately suppressed per institutional practice will be permitted

          -  Have any other acute or chronic medical or psychiatric condition, including recent or
             active suicidal ideation or behavior, or a laboratory abnormality that may increase
             the risk associated with study participation or investigational product administration
             or may interfere with the interpretation of study results and, in the judgment of the
             investigator, would make the subject inappropriate for entry into this study.

          -  Have known active inflammatory gastrointestinal disease, previous gastric resection,
             or lap band dysphagia, short bowel syndrome, gastroparesis or other conditions that
             limit ingestion or gastrointestinal absorption of drugs administered orally.

          -  Has a known medical history of progressive multifocal leukoencephalopathy (PML)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:16 weeks
Safety Issue:
Description:Progression free survival includes both disease progression (as defined by RECIST 1.1) and death from any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Chondrosarcoma
  • Chondrosarcoma, Grade 2
  • Chondrosarcoma, Grade 3
  • IDH1 Gene Mutation
  • IDH1 Mutant Chondrosarcoma
  • AG-120
  • locally advanced chondrosarcoma
  • metastatic chondrosarcoma
  • Memorial Sloan Kettering Cancer Center
  • 19-393

Last Updated

February 18, 2020