Clinical Trials /

QUILT-3.031: AMG 337 in Subjects With Advanced or Metastatic Clear Cell Sarcoma

NCT03132155

Description:

This is a phase 2 study that will assess the efficacy of AMG 337 in subjects with advanced or metastatic clear cell sarcoma that contains the EWSR1-ATF1 gene fusion.

Related Conditions:
  • Clear Cell Sarcoma of Soft Tissue
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: QUILT-3.031: AMG 337 in Subjects With Advanced or Metastatic Clear Cell Sarcoma
  • Official Title: A Phase 2 Study of AMG 337 in Subjects With Advanced or Metastatic Clear Cell Sarcoma That Contains the Ewing Sarcoma Breakpoint Region 1-activating Transcription Factor-1 (EWSR1-ATF1) Gene Fusion

Clinical Trial IDs

  • ORG STUDY ID: QUILT-3.031
  • NCT ID: NCT03132155

Conditions

  • Clear Cell Sarcoma

Interventions

DrugSynonymsArms
AMG 337AMG 337

Purpose

This is a phase 2 study that will assess the efficacy of AMG 337 in subjects with advanced or metastatic clear cell sarcoma that contains the EWSR1-ATF1 gene fusion.

Detailed Description

      The phase 2 study will assess efficacy of AMG 337 in subjects with advanced or metastatic
      clear cell sarcoma that contains the EWSR1-ATF1 gene fusion. The study will be conducted
      using Simon's two-stage optimal design. The null hypothesis of Simon's two-stage design
      states that the ORR will be ≤ 40% (poor response) and will be tested against a one-sided
      alternative.
    

Trial Arms

NameTypeDescriptionInterventions
AMG 337ExperimentalAMG 337 will be administered in patients with advanced or metastatic clear cell sarcoma
  • AMG 337

Eligibility Criteria

        Inclusion Criteria:

          1. Able to understand and provide a signed informed consent that fulfills the relevant
             Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.

          2. Able to attend required study visits and return for adequate follow-up, as required by
             this protocol.

          3. Able to self-administer AMG 337 as a whole capsule by mouth every day.

          4. Age ≥ 16 years.

          5. Histologically confirmed, unresectable, locally advanced or metastatic tumors that
             contain the EWSR1-ATF1 gene fusion, as determined by fluorescent in situ hybridization
             (FISH) and confirmed by RNA sequencing (RNAseq).

          6. Have measurable disease evaluable in accordance with RECIST Version 1.1.

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          8. Must have a recent Formalin-fixed paraffin-embedded (FFPE) tumor biopsy specimen that
             was obtained following the conclusion of the most recent anticancer treatment. If an
             historic specimen is not available, the subject must be willing to undergo a biopsy
             during the screening period.

          9. Must be willing to undergo a biopsy during the treatment period, if considered safe by
             the investigator.

         10. Ability to attend required study visits and return for adequate follow-up, as required
             by this protocol.

         11. Hematologic function, as follows:

               1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.

               2. Platelet count ≥ 50 × 109/L.

               3. Hemoglobin > 8 g/dL.

               4. Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 × upper limit of
                  normal (ULN), except for subjects on anticoagulation therapy for venous
                  thromboembolism.

         12. Renal function, as follows:

             a. Calculated creatinine clearance > 30 mL/min.

         13. Hepatic function, as follows:

               1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN
                  and total bilirubin < 1.5 × ULN.

               2. Alkaline phosphatase (ALP) < 2 × ULN (≤ 5 × ULN if bone or liver metastases are
                  present)

         14. Agreement to practice effective contraception (both male and female subjects, if the
             risk of conception exists).

        Exclusion Criteria:

          1. Assessed by the investigator to be unable or unwilling to comply with the requirements
             of the protocol.

          2. Inability to attend required study visits and return for adequate follow-up, as
             required for this protocol.

          3. Known hypersensitivity to any component of the study medication(s).

          4. Women who are nursing, pregnant, or planning to become pregnant during the duration of
             the study.

          5. Current diagnosis or history of a second neoplasm, except the following:

             a. Adequately treated non-melanoma skin cancer, curatively treated in situ disease, or
             other solid tumors curatively treated with no evidence of disease for ≥ 2 years.

          6. History of bleeding diathesis.

          7. Uncontrolled hypertension (systolic > 160 mmHg and/or diastolic > 100 mmHg) or
             clinically significant cardiovascular disease, cerebrovascular accident/stroke, or
             myocardial infarction within 6 months before study day 1; unstable angina; congestive
             heart failure of New York Heart Association grade 2 or higher; or serious cardiac
             arrhythmia requiring medication.

          8. Baseline ECG Fridericia's formula QTcF > 470 ms.

          9. Active infection requiring intravenous (IV) antibiotics within 2 weeks before study
             day 1.

         10. Significant gastrointestinal disorder (eg, Crohn's disease, ulcerative colitis,
             extensive gastrointestinal resection) that in the opinion of the Investigator may
             influence drug absorption.

         11. Positive result of screening test for human immunodeficiency virus (HIV).

         12. Evidence of acute hepatitis B and C. Subjects with chronic hepatitis B or C are
             eligible if their condition is stable and, in the opinion of the investigator, would
             not pose a risk to subject safety.

         13. Toxicities from prior anti-tumor therapy not resolved to CTCAE Version 4.03 grade 0 or
             1.

             a. Grade 2 toxicities from prior anti-tumor therapy that are considered irreversible
             (defined as having been present or stable for > 4 weeks), such as stable grade 2
             peripheral neuropathy or ifosfamide-related proteinuria, may be allowed if they are
             not otherwise described in the exclusion criteria.

         14. Participation in this study or in an investigational study and/or procedure with any
             molecularly targeted agents reported to inhibit Mesenchymal epithelial transition
             factor (MET) within 14 days before study day 1.

         15. Anti-tumor therapy, including chemotherapy, antibody therapy, retinoid therapy, or
             other investigational therapy within 14 days before study day 1.

         16. Therapeutic or palliative radiation therapy within 14 days before study day 1.

         17. Major surgery within 28 days before study day 1.

         18. Any comorbidity that in the opinion of the investigator may increase the risk of
             toxicity.

         19. Concurrent or prior use of a strong CYP3A4 inhibitor within 14 days before study day
             1, including the following: ketoconazole, itraconazole, clarithromycin, indinavir,
             nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole.

         20. Concurrent or prior ingestion of grapefruit or grapefruit products, or other foods
             known to inhibit CYP3A4 within 7 days before study day 1.

         21. Concurrent or prior use of strong CYP3A4 inducers within 28 days before study day 1,
             including the following: phenytoin, carbamazepine, rifampin, rifabutin, rifapentin,
             phenobarbital, or the herbal supplement St. John's Wort.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:1 year
Safety Issue:
Description:Confirmed ORR (confirmed complete response or partial response) will be evaluated in accordance with RECIST Version 1.1.

Secondary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability)
Time Frame:1 year
Safety Issue:
Description:To evaluate the safety of AMG 337 based on grade 3 or 4 non-hematologic toxicity.
Measure:Progression-free Survival (PFS)
Time Frame:1 year
Safety Issue:
Description:To determine PFS, evaluated in accordance with RECIST Version 1.1.
Measure:Overall Survival (OS)
Time Frame:1 year
Safety Issue:
Description:To determine OS, defined as the time from the date of the first administration of therapy to the date of death.
Measure:Duration of Response (DOR)
Time Frame:1 year
Safety Issue:
Description:To determine DOR, measured by RECIST Version 1.1.
Measure:Disease Control Rate (DCR)
Time Frame:4 months
Safety Issue:
Description:To determine DCR (confirmed CR, PR, or SD) lasting for at least 4 months.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NantPharma, LLC

Last Updated

January 3, 2018