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

Primary Purpose

Clear Cell Sarcoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AMG 337
Sponsored by
NantPharma, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clear Cell Sarcoma

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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) or other diagnostic methods 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.

Sites / Locations

  • Chan Soon-Shiong Institute for Medicine
  • The University of Texas, MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AMG 337

Arm Description

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

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
Confirmed ORR (confirmed complete response or partial response) will be evaluated in accordance with RECIST Version 1.1 by BICR.

Secondary Outcome Measures

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

Full Information

First Posted
April 20, 2017
Last Updated
December 9, 2022
Sponsor
NantPharma, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03132155
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
Prematurely terminated due to lack of therapeutic effect
Study Start Date
May 2, 2018 (Actual)
Primary Completion Date
August 13, 2021 (Actual)
Study Completion Date
September 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NantPharma, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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 single arm study will assess efficacy of AMG 337 (based on confirmed ORR) in subjects with advanced or metastatic clear cell sarcoma that contains the EWSR1-ATF1 gene fusion, as determined by fluorescent in situ hybridization (FISH) or other diagnostic methods and confirmed by RNA sequencing (RNAseq).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clear Cell Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AMG 337
Arm Type
Experimental
Arm Description
AMG 337 will be administered in patients with advanced or metastatic clear cell sarcoma
Intervention Type
Drug
Intervention Name(s)
AMG 337
Intervention Description
6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one•hydrate (1:1)
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Confirmed ORR (confirmed complete response or partial response) will be evaluated in accordance with RECIST Version 1.1 by BICR.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability)
Description
To evaluate the safety of AMG 337 based on grade 3 or 4 non-hematologic toxicity.
Time Frame
1 year
Title
Progression-free Survival (PFS)
Description
To determine PFS, evaluated in accordance with RECIST Version 1.1 BICR.
Time Frame
1 year
Title
Overall Survival (OS)
Description
To determine OS, defined as the time from the date of the first administration of therapy to the date of death.
Time Frame
1 year
Title
Duration of Response (DOR)
Description
To determine DOR, measured by RECIST Version 1.1 by BICR.
Time Frame
1 year
Title
Disease Control Rate (DCR)
Description
To determine DCR (confirmed CR, PR, or SD) lasting for at least 4 months by BICR.
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. Able to attend required study visits and return for adequate follow-up, as required by this protocol. Able to self-administer AMG 337 as a whole capsule by mouth every day. Age ≥ 16 years. Histologically confirmed, unresectable, locally advanced or metastatic tumors that contain the EWSR1-ATF1 gene fusion, as determined by fluorescent in situ hybridization (FISH) or other diagnostic methods and confirmed by RNA sequencing (RNAseq). Have measurable disease evaluable in accordance with RECIST Version 1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 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. Must be willing to undergo a biopsy during the treatment period, if considered safe by the investigator. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. Hematologic function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L. Platelet count ≥ 50 × 109/L. Hemoglobin > 8 g/dL. Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 × upper limit of normal (ULN), except for subjects on anticoagulation therapy for venous thromboembolism. Renal function, as follows: a. Calculated creatinine clearance > 30 mL/min. Hepatic function, as follows: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN and total bilirubin < 1.5 × ULN. Alkaline phosphatase (ALP) < 2 × ULN (≤ 5 × ULN if bone or liver metastases are present) Agreement to practice effective contraception (both male and female subjects, if the risk of conception exists). Exclusion Criteria: Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol. Inability to attend required study visits and return for adequate follow-up, as required for this protocol. Known hypersensitivity to any component of the study medication(s). Women who are nursing, pregnant, or planning to become pregnant during the duration of the study. 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. History of bleeding diathesis. 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. Baseline ECG Fridericia's formula QTcF > 470 ms. Active infection requiring intravenous (IV) antibiotics within 2 weeks before study day 1. Significant gastrointestinal disorder (eg, Crohn's disease, ulcerative colitis, extensive gastrointestinal resection) that in the opinion of the Investigator may influence drug absorption. Positive result of screening test for human immunodeficiency virus (HIV). 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. 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. 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. Anti-tumor therapy, including chemotherapy, antibody therapy, retinoid therapy, or other investigational therapy within 14 days before study day 1. Therapeutic or palliative radiation therapy within 14 days before study day 1. Major surgery within 28 days before study day 1. Any comorbidity that in the opinion of the investigator may increase the risk of toxicity. 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. Concurrent or prior ingestion of grapefruit or grapefruit products, or other foods known to inhibit CYP3A4 within 7 days before study day 1. 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.
Facility Information:
Facility Name
Chan Soon-Shiong Institute for Medicine
City
El Segundo
State/Province
California
ZIP/Postal Code
90245
Country
United States
Facility Name
The University of Texas, MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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