Clear Cell SarcomaPhase 2NCT03132155

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

A Phase 2 study testing AMG 337 in people with Clear Cell Sarcoma, run by NantPharma, LLC at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 16 years and older
Conditions the study is for: Clear Cell Sarcoma
What is being tested?: AMG 337
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 2 sitesUnited States
Study dates: 29 Aug 2018to 21 Sep 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

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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:
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).

Who cannot join

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:
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.

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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.
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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Chan Soon-Shiong Institute for Medicine
El Segundo, California, 90245
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the 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).

Conditions: Clear Cell Sarcoma
Being tested: AMG 337
Medical subject headings: Sarcoma, Clear Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AMG 337Drug
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)

Study groups in NCT03132155
Study group	Role	What they receive
AMG 337	Experimental	AMG 337 will be administered in patients with advanced or metastatic clear cell sarcoma Receives: Drug: AMG 337

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 1 year

Secondary outcomes (1)

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.
Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Aug 201821 Sep 2021

First posted27 Apr 2017
Study start29 Aug 2018
Primary completion13 Aug 2021
Study completion21 Sep 2021

Why it stopped: Prematurely terminated due to lack of therapeutic effect

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Clear Cell SarcomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03132155
Sponsor's protocol ID: QUILT-3.031
Status last verified: May 2024
First submitted: 20 Apr 2017
Last updated: 24 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Clear Cell Chondrosarcoma in Italy
Chondrosarcoma
RecruitingPhase 1
A Study of MGC026 in Participants With Advanced Solid Tumors
Advanced Solid Tumor, Advanced Cancer
RecruitingPhase 2
A Phase II Trial of Tebentafusp in HLA-A*02:01 Positive Patients With Advanced Clear Cell Sarcoma
HLA-A*0201 Positive Cells Present, Clear Cell Sarcoma (CCS)
Active, not recruitingPhase 3
Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer
Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma
Active, not recruitingPhase 2
Agnostic Therapy in Rare Solid Tumors
Urachal Cancer, Parathyroid Carcinoma

All Clear Cell Sarcoma trials

Study at a glance

From the registry record, last updated by the sponsor on 24 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03132155
Acronym / sponsor ID: QUILT-3.031
Conditions: Clear Cell Sarcoma
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Prematurely terminated due to lack of therapeutic effect
Enrolment: 8 participants (actual)
Lead sponsor: NantPharma, LLCIndustry (pharma, biotech, devices)
Study start: 29 Aug 2018 (actual)
Primary completion: 13 Aug 2021 (actual)
Study completion: 21 Sep 2021 (actual)
First posted: 27 Apr 2017 (actual)
Results: Posted 24 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
AMG 337	Experimental	Drug: AMG 337AMG 337 will be administered in patients with advanced or metastatic clear cell sarcoma

Who may qualify

Ages: 16 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (21 listed)

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).

Key exclusion criteria (23 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AMG 3376-{(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)	Drug	AMG 337

Primary outcome

Objective Response Rate (ORR)
Time frame: 1 year
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

1 secondary outcome

Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability)
Time frame: 1 year

Results and safety

Results posted to the registry on 24 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AMG 337	8	0

Primary outcome: Objective Response Rate (ORR)

Time frame: 1 year. Count of participants. Unit: Participants

Measure	AMG 337 n = 8
Partial Response	1
Stable Disease	1
Progressive Disease	5
Imaging not available to evaluate	1

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Non-serious AEs were followed for 30 days after the subject's last dose of study treatment, up to 13 months. Non-serious grade 3 or 4 AEs were followed until resolution or stabilization, up to 13 months. All SAEs that had not resolved upon discontinuation of the subject's participation in the study were followed until recovered, recovered with sequelae, not recovered (death due to other cause), death (due to the SAE), lost to follow-up. All-cause mortality approximately 3 years.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AMG 337	3 of 8 (37.5%)	8 of 8 (100%)	4 of 8

Limitations and caveats (from the sponsor): The study was terminated early due to low enrollment. Only the safety data is provided.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Clear Cell Sarcoma

Active, not recruiting
Clear Cell Chondrosarcoma in Italy
Chondrosarcoma
RecruitingPhase 1
A Study of MGC026 in Participants With Advanced Solid Tumors
Advanced Solid Tumor, Advanced Cancer
RecruitingPhase 2
A Phase II Trial of Tebentafusp in HLA-A*02:01 Positive Patients With Advanced Clear Cell Sarcoma
HLA-A*0201 Positive Cells Present, Clear Cell Sarcoma (CCS)
Active, not recruitingPhase 3
Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer
Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma
Active, not recruitingPhase 2
Agnostic Therapy in Rare Solid Tumors
Urachal Cancer, Parathyroid Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AMG 337 in people with Clear Cell Sarcoma, run by NantPharma, LLC at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03132155.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2024.