Clear Cell Sarcoma

1. Disease Information

1.1 Concise overview (current understanding)

Clear cell sarcoma (CCS) is a rare, aggressive malignant soft-tissue sarcoma that typically arises in deep soft tissues associated with tendons/aponeuroses and most often occurs in the extremities (notably lower extremity/foot–ankle region). It shows melanocytic differentiation and is a major diagnostic mimic of malignant melanoma. (cazzato2025clearcellsarcoma pages 1-2, thway2012tumorswithewsr1creb1 pages 3-5, gonzaga2018theepidemiologyand pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

Direct abstract quote (molecularly defining feature): “Clear cell sarcoma (CCS)… is characterized by the expression of the oncogenic driver fusion gene EWSR1::ATF1.” (Mae et al., 2023, Cancer Research Communications, published Jul 2023, https://doi.org/10.1158/2767-9764.crc-22-0518) (mae2023targetingtheclear pages 1-2)

1.2 Key identifiers

The following identifiers were not captured in the retrieved excerpts, so cannot be reliably asserted here: - OMIM / Orphanet / ICD-10 / ICD-11 / MONDO: not available in current evidence. - MeSH: ClinicalTrials.gov condition browse lists MeSH term “Sarcoma, Clear Cell” (MeSH ID D018227) for this condition. (NCT05963035 chunk 1)

1.3 Synonyms / alternative names

• Clear cell sarcoma of soft tissue (CCS) (cazzato2025clearcellsarcoma pages 1-2)
• Clear cell sarcoma of tendons and aponeuroses (grothues2024prognosticfactorsin pages 1-2)
• “Malignant melanoma of soft parts” / “soft tissue melanoma” (historical) (mae2023targetingtheclear pages 1-2, gonzaga2018theepidemiologyand pages 1-2)

1.4 Evidence source type

Most disease-level definitions and management statements in this report derive from aggregated resources (reviews), registry/cohort analyses, and clinical trial registry entries rather than single-patient EHR-derived sources. (cazzato2025clearcellsarcoma pages 1-2, gonzaga2018theepidemiologyand pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2, NCT05963035 chunk 1)

2. Etiology

2.1 Disease causal factors (genetic/mechanistic)

CCS is primarily a fusion-driven sarcoma, most commonly defined by EWSR1::ATF1 (EWSR1 fused to ATF1), usually arising from t(12;22)(q13;q12); rarer variants include EWSR1::CREB1 or EWSR1::CREM. (mae2023targetingtheclear pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

Direct abstract quote (fusion defines and drives disease): “It is defined and driven by expression of… translocation-generated fusion oncogenes, the most common of which is EWSR1::ATF1.” (Ozenberger et al., 2023, Cancers, published Dec 2023, https://doi.org/10.3390/cancers15245750) (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

Frequency of hallmark fusion: One 2023 genomic/functional review states: “Nearly 90% of CCS harbor an EWSR1-ATF1 translocation-mediated fusion gene, although EWSR1-CREB1 is also observed.” (Rasmussen et al., 2023, British Journal of Cancer, published Mar 2023, https://doi.org/10.1038/s41416-023-02222-0) (rasmussen2023functionalgenomicsof pages 1-2)

2.2 Risk factors

No robust environmental/behavioral risk factors were identified in the retrieved evidence. Available evidence emphasizes oncogenic fusion as the major causal event. (rasmussen2023functionalgenomicsof pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

2.3 Protective factors / gene–environment interaction

No protective factors or gene–environment interactions were identified in the retrieved evidence. (rasmussen2023functionalgenomicsof pages 1-2)

3. Phenotypes

3.1 Core clinical phenotype spectrum

Common presentations include a deep soft-tissue mass in an extremity and association with tendons/aponeuroses. Pain may be present (one review describes “a painful, rapidly growing mass” in typical locations). (bianco2024ewsr1atf1translocationa pages 12-13, gonzaga2018theepidemiologyand pages 1-2)

Typical sites / demographics (examples): - CCS “arises in muscle compartments, tendons, or aponeuroses, most frequently in the extremities.” (Ozenberger et al., 2023) (ozenberger2023ewsr1atf1orchestratesthe pages 1-2) - In an NCDB cohort, lower limb/hip was the most frequent primary site (53%). (Gonzaga et al., 2018, https://doi.org/10.1007/s00432-018-2693-6) (gonzaga2018theepidemiologyand pages 1-2)

3.2 Suggested HPO terms (non-exhaustive; based on clinical descriptions)

Because the retrieved evidence is not structured as HPO annotations, the following are suggested mappings from described clinical manifestations: - Soft tissue mass → Soft tissue neoplasm (candidate HPO mapping; specific HPO ID not available in evidence) - Painful mass → Pain (candidate) - Local recurrence / metastasis → Neoplasm metastasis (candidate)

Note: Exact HPO IDs require ontology lookup not performed in this run.

3.3 Quality-of-life impact

Formal QoL instruments (e.g., EQ-5D/SF-36) were not reported in the retrieved CCS-specific papers; however, QoL is included as an outcome in at least one CCS immunotherapy trial protocol (EORTC QLQ-C30 and EQ-5D). (NCT04274023 chunk 1)

4. Genetic / Molecular Information

4.1 Causal genes / chromosomal abnormalities

• EWSR1::ATF1 fusion (EWSR1 and ATF1 genes) from t(12;22)(q13;q12) is the central hallmark for CCS. (mae2023targetingtheclear pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)
• Rarer: EWSR1::CREB1 and EWSR1::CREM. (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

4.2 Pathogenic variant class

The dominant pathogenic event is a structural rearrangement generating an oncogenic fusion transcription factor (chimeric transcriptional regulator). (mae2023targetingtheclear pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

4.3 Functional consequences / downstream programs

Mechanistically, evidence supports that EWSR1::ATF1 reprograms transcription and is sufficient to initiate sarcomagenesis in model systems. (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

Direct abstract quote (transcriptional reprogramming): “The EWSR1::ATF1 fusion oncoprotein reprograms transcription.” (Ozenberger et al., 2023) (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

4.4 Additional recurrent genomic features (from functional genomics)

A 2023 functional genomics study reports frequent copy gains involving MITF and MYC loci in human CCS samples (e.g., MYC gain in 62% and MITF gain in 55% of a set of tumors described in the excerpt). (rasmussen2023functionalgenomicsof pages 1-2)

5. Environmental Information

No specific environmental/lifestyle/infectious contributors were identified in the retrieved evidence. CCS is primarily discussed as a fusion-oncogene-driven malignancy. (rasmussen2023functionalgenomicsof pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

6. Mechanism / Pathophysiology

6.1 High-level causal chain (fusion → transcriptional/epigenetic rewiring → phenotype)

1. Chromosomal translocation generates EWSR1::ATF1 fusion. (mae2023targetingtheclear pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)
2. Fusion functions as an aberrant transcriptional regulator that reprograms transcription and sustains tumor state. (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)
3. Tumor develops melanocytic differentiation (shared IHC markers with melanoma) and demonstrates aggressive behavior with local recurrence and metastasis risk. (thway2012tumorswithewsr1creb1 pages 3-5, gonzaga2018theepidemiologyand pages 1-2)

6.2 Epigenetic/transcriptional dependencies and therapeutic implications (recent)

A 2023 study used high-throughput screening and found that HDAC inhibition can suppress the fusion program.

Direct abstract quote (screening and lead drug): “we performed a high-throughput drug screening, finding that the histone deacetylase inhibitor vorinostat exerted an antiproliferation effect with the reduced expression of EWSR1::ATF1.” (Mae et al., 2023, https://doi.org/10.1158/2767-9764.crc-22-0518) (mae2023targetingtheclear pages 1-2)

6.3 Suggested GO / CL terms (conceptual; require ontology lookup)

Based on the evidence that CCS is fusion-transcription-factor driven and involves melanocytic differentiation markers: - GO Biological Process (candidate): regulation of transcription, chromatin organization, melanocyte differentiation - CL (candidate): neural crest-derived cell lineages (proposed by epigenetic/3D regulation studies; not fully extracted here)

7. Anatomical Structures Affected

7.1 Organ/tissue level

• Predominantly deep soft tissue of extremities; commonly near tendons and aponeuroses. (cazzato2025clearcellsarcoma pages 1-2, thway2012tumorswithewsr1creb1 pages 3-5, gonzaga2018theepidemiologyand pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

7.2 Suggested UBERON terms (conceptual)

• Extremity soft tissue; tendon; aponeurosis (exact UBERON IDs not retrieved).

8. Temporal Development

8.1 Onset

Typically affects adolescents/young adults but can occur across a broad range. Reported mean age 22 (range 2–83) in one 2023 review; median age 39 in NCDB (1973–2014 cohort analysis); median age 42 in a 2024 single-center cohort. (rasmussen2023functionalgenomicsof pages 1-2, gonzaga2018theepidemiologyand pages 1-2, grothues2024prognosticfactorsin pages 1-2)

8.2 Progression

Evidence emphasizes frequent local recurrence and late metastasis, with poor long-term survival in many cohorts. (rasmussen2023functionalgenomicsof pages 1-2, gonzaga2018theepidemiologyand pages 1-2, grothues2024prognosticfactorsin pages 1-2)

9. Inheritance and Population

9.1 Epidemiology (key quantitative data)

CCS is very rare. One paper states it is “less than one percent of soft-tissue sarcomas” and reports “fewer than 100 cases… annually in the United States.” (Ozenberger et al., 2023) (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

A SEER-based analysis reported population-adjusted incidence range 0.012/100,000 to 0.027/100,000 (2000–2019). (gonzaga2018theepidemiologyand pages 1-2)

9.2 Demographics

NCDB review: median age 39, sexes approximately equal, and race distribution 78% Caucasian and 15% Black. (gonzaga2018theepidemiologyand pages 1-2)

9.3 Inheritance

CCS is not presented as an inherited Mendelian disorder in the retrieved evidence; it is driven by a somatic fusion. Germline predisposition was not identified here. (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

10. Diagnostics

10.1 Pathology and immunohistochemistry

CCS is a melanoma mimic; classic IHC profile overlaps melanoma.

From a high-citation pathology review: “most CCSs show diffuse S100 protein, HMB45, MelanA and MiTF expression and are immunohistochemically indistinguishable from melanoma.” (Thway & Fisher, 2012, Am J Surg Pathol, https://doi.org/10.1097/pas.0b013e31825485c5) (thway2012tumorswithewsr1creb1 pages 3-5)

10.2 Molecular diagnostics

Molecular confirmation is emphasized for distinguishing CCS from melanoma:

Direct abstract quote: “the use of fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) is essential for diagnosis and distinguishing CCS from primary and/or metastatic melanoma.” (Gonzaga et al., 2018, https://doi.org/10.1007/s00432-018-2693-6) (gonzaga2018theepidemiologyand pages 1-2)

10.3 Differential diagnosis

Primary differential is malignant melanoma due to shared morphology and melanocytic markers; molecular demonstration of EWSR1 fusion is key. (cazzato2025clearcellsarcoma pages 1-2, thway2012tumorswithewsr1creb1 pages 3-5, gonzaga2018theepidemiologyand pages 1-2)

10.4 Emerging/adjunct markers and tools

Recent narrative review emphasizes PRAME as an adjunct marker in differential diagnosis with melanoma, while noting PRAME positivity is relatively rare in CCS. (cazzato2025clearcellsarcoma pages 1-2, cazzato2025clearcellsarcoma pages 8-10)

10.5 Imaging and staging innovations (real-world implementation)

A prospective diagnostic study is evaluating melanin-targeted PET imaging.

• NCT05963035 (posted 2023-07-27; start 2023-06-21): prospective study of 18F-PFPN PET/MR versus 18F-FDG for diagnosis and staging in CCS of soft tissue (planned n=10). (ClinicalTrials.gov record) (NCT05963035 chunk 1)

11. Outcomes / Prognosis

11.1 Survival statistics

Multiple sources converge on poor long-term outcomes.

• A widely repeated summary: 5-year ~50%, 10-year ~38% overall survival. (mae2023targetingtheclear pages 1-2, bianco2024ewsr1atf1translocationa pages 12-13, gonzaga2018theepidemiologyand pages 1-2, ozenberger2023ewsr1atf1orchestratesthe pages 1-2)
• A 2024 single-center cohort (43 CCS/GINET patients) reported: “median follow-up of 35mo and a 5y-OS-rate of 42%.” (Grothues et al., 2024, https://doi.org/10.1007/s00432-024-05980-3) (grothues2024prognosticfactorsin pages 1-2)

11.2 Metastasis and lymphatic spread (quantitative)

• 2024 cohort: “18.6% of patients showed lymphatic spread and 20.9% distant metastases.” (Grothues et al., 2024) (grothues2024prognosticfactorsin pages 1-2)
• NCDB review summarizes that lymph node metastases are unusually frequent for STS (estimated 12–43% across prior literature) and reports 15% distant organ metastases in the cohort (lung most common 4%). (gonzaga2018theepidemiologyand pages 1-2)

11.3 Prognostic factors (recent quantitative evidence)

• Initial metastatic disease is strongly adverse: “Presence of initial M+ was associated with a dismal survival of 1.4 years (M+) vs 7.1 years (M0; p < .001).” (Grothues et al., 2024) (grothues2024prognosticfactorsin pages 1-2)
• Completeness of surgery matters in localized disease: “Final R0 status correlated significantly… with longer survival… (N0M0, 5-yr OS 0% vs 64% [R+ vs R0]).” (Grothues et al., 2024) (grothues2024prognosticfactorsin pages 1-2)

12. Treatment

12.1 Current standard of care / real-world implementation

Across reviews and cohort analyses, surgery with negative margins is the main curative-intent treatment for localized CCS. (cazzato2025clearcellsarcoma pages 1-2, gonzaga2018theepidemiologyand pages 1-2, grothues2024prognosticfactorsin pages 1-2)

• NCDB treatment patterns: surgery 83%, radiation 34%, chemotherapy 20%. (gonzaga2018theepidemiologyand pages 1-2)

12.2 Radiotherapy and chemotherapy

Conventional radiotherapy and chemotherapy are often described as having limited benefit.

• “Traditional chemo- and radiotherapies have minimal benefit in CCS.” (Bianco et al., 2024, https://doi.org/10.3390/ijms252413693) (bianco2024ewsr1atf1translocationa pages 12-13)
• 2024 cohort: “Radiation and systemic treatment had limited antitumor effects…” (Grothues et al., 2024) (grothues2024prognosticfactorsin pages 1-2)

12.3 Investigational and emerging strategies (2023–2024 emphasis)

Epigenetic/transcriptional targeting is supported by preclinical evidence: - HDAC inhibitor vorinostat suppressing EWSR1::ATF1 and inhibiting proliferation in CCS models. (mae2023targetingtheclear pages 1-2)

Targeted therapy and immunotherapy are being explored due to lack of effective systemic options in metastatic disease. (cazzato2025clearcellsarcoma pages 8-10, grothues2024prognosticfactorsin pages 1-2)

12.4 Clinical trials (selected, with real-world status)

• NCT04593758 (posted 2020-10-20; completion 2023-03-09): devimistat (CPI-613) + hydroxychloroquine for relapsed/refractory CCS; phase I/II; n=16; completed. (NCT04593758 chunk 1)
• NCT04274023 (posted 2020-02-18; status updated 2024-02-01): anti-PD-1 TSR-042 in advanced CCS; phase II; terminated due to enrollment difficulty; n=3. (NCT04274023 chunk 1)
• NCT03132155 (results posted 2024-05-24): AMG 337 for advanced/metastatic CCS with EWSR1-ATF1 fusion; phase II; “terminated due to lack of therapeutic effect”; n=8. (NCT03132155 chunk 1)
• NCT04458922 (results first posted 2023-10-23): atezolizumab phase II study in CCS/chondrosarcoma; includes tumor microenvironment correlatives (CD8 and PD-1/PD-L1); active not recruiting; n=27 total. (NCT04458922 chunk 1)

MAXO term suggestions (conceptual): - Surgical excision; radiotherapy; systemic chemotherapy; immune checkpoint inhibitor therapy; targeted therapy (MET inhibition); PET imaging (diagnostic). (Trial and review evidence supports these intervention classes) (cazzato2025clearcellsarcoma pages 8-10, NCT05963035 chunk 1, NCT04274023 chunk 1, NCT04458922 chunk 1)

13. Prevention

No established primary prevention strategies were identified in the retrieved evidence; CCS is rare and primarily defined by a somatic fusion event. Secondary prevention is effectively early detection and expert referral for accurate diagnosis and complete surgical management. (gonzaga2018theepidemiologyand pages 1-2, grothues2024prognosticfactorsin pages 1-2)

14. Other Species / Natural Disease

No comparative veterinary/natural disease evidence was retrieved in this run.

15. Model Organisms

Evidence in this run supports the existence of mouse genetic models and preclinical approaches centered on EWSR1::ATF1-driven tumor programs (including studies describing initiation of sarcomagenesis and transcriptome recapitulation). (ozenberger2023ewsr1atf1orchestratesthe pages 1-2)

Structured summary table (for knowledge base ingestion)

The following table consolidates key facts (definition, epidemiology, diagnostics, prognosis, therapies, and NCT trials) into a single scaffold.

Table: This table compiles the core disease-definition, epidemiology, diagnostics, and treatment/trial information for clear cell sarcoma using only the retrieved evidence snippets and clinical trial records. It is useful as a compact knowledge-base scaffold with direct context-ID citations for traceability.

References

1. (thway2012tumorswithewsr1creb1 pages 3-5): Khin Thway and Cyril Fisher. Tumors with ewsr1-creb1 and ewsr1-atf1 fusions: the current status. The American Journal of Surgical Pathology, 36:e1–e11, Jul 2012. URL: https://doi.org/10.1097/pas.0b013e31825485c5, doi:10.1097/pas.0b013e31825485c5. This article has 267 citations.

2. (gonzaga2018theepidemiologyand pages 1-2): M. Isabel Gonzaga, Leah Grant, Christina Curtin, Jonathan Gootee, Peter Silberstein, and Elida Voth. The epidemiology and survivorship of clear cell sarcoma: a national cancer database (ncdb) review. Journal of Cancer Research and Clinical Oncology, 144:1711-1716, Jun 2018. URL: https://doi.org/10.1007/s00432-018-2693-6, doi:10.1007/s00432-018-2693-6. This article has 72 citations and is from a peer-reviewed journal.

3. (ozenberger2023ewsr1atf1orchestratesthe pages 1-2): Benjamin B. Ozenberger, Li Li, Emily R. Wilson, Alexander J. Lazar, Jared J. Barrott, and Kevin B. Jones. Ewsr1::atf1 orchestrates the clear cell sarcoma transcriptome in human tumors and a mouse genetic model. Cancers, 15:5750, Dec 2023. URL: https://doi.org/10.3390/cancers15245750, doi:10.3390/cancers15245750. This article has 14 citations.

4. (cazzato2025clearcellsarcoma pages 1-2): Gerardo Cazzato, Francesco Piscazzi, Alessandra Filosa, Anna Colagrande, Paolo Del Fiore, Francesca Ambrogio, Chiara Battilotti, Andrea Danese, Serena Federico, and Fortunato Cassalia. Clear cell sarcoma (ccs) of the soft tissue: an update narrative review with emphasis on the utility of prame in differential diagnosis. Journal of Clinical Medicine, 14:1233, Feb 2025. URL: https://doi.org/10.3390/jcm14041233, doi:10.3390/jcm14041233. This article has 8 citations.

5. (mae2023targetingtheclear pages 1-2): Hirokazu Mae, Hidetatsu Outani, Yoshinori Imura, Ryota Chijimatsu, Akitomo Inoue, Yuki Kotani, Naohiro Yasuda, Sho Nakai, Takaaki Nakai, Satoshi Takenaka, and Seiji Okada. Targeting the clear cell sarcoma oncogenic driver fusion gene ewsr1::atf1 by hdac inhibition. Cancer Research Communications, 3:1152-1165, Jul 2023. URL: https://doi.org/10.1158/2767-9764.crc-22-0518, doi:10.1158/2767-9764.crc-22-0518. This article has 15 citations and is from a peer-reviewed journal.

6. (NCT05963035 chunk 1): Clinical Application of 18F-PFPN PET Imaging in Diagnosis and Staging of Clear Cell Sarcoma of Soft Tissue. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. 2023. ClinicalTrials.gov Identifier: NCT05963035

7. (grothues2024prognosticfactorsin pages 1-2): Janik Grothues, Jendrik Hardes, Abbas Agaimy, Stephane Collaud, Lars Podleska, Farhad Farzalyev, Nina Myline Engel, Rainer Hamacher, Benjamin Fletcher, Christoph Pöttgen, Stefanie Bertram, Hans-Ulrich Schildhaus, Arne Streitbürger, Sebastian Bauer, and Johanna Falkenhorst. Prognostic factors in clear cell sarcoma: an analysis of soft tissue sarcoma in 43 cases. Journal of Cancer Research and Clinical Oncology, Nov 2024. URL: https://doi.org/10.1007/s00432-024-05980-3, doi:10.1007/s00432-024-05980-3. This article has 6 citations and is from a peer-reviewed journal.

8. (rasmussen2023functionalgenomicsof pages 1-2): Samuel V. Rasmussen, Agnieszka Wozniak, Melvin Lathara, Joshua M. Goldenberg, Benjamin M. Samudio, Lissett R. Bickford, Kiyo Nagamori, Hollis Wright, Andrew D. Woods, Shefali Chauhan, Che-Jui Lee, Erin R. Rudzinski, Michael K. Swift, Tadashi Kondo, David E. Fisher, Evgeny Imyanitov, Isidro Machado, Antonio Llombart-Bosch, Irene L. Andrulis, Nalan Gokgoz, Jay Wunder, Hiroshi Mirotaki, Takuro Nakamura, Ganapati Srinivasa, Khin Thway, Robin L. Jones, Paul H. Huang, Noah E. Berlow, Patrick Schöffski, and Charles Keller. Functional genomics of human clear cell sarcoma: genomic, transcriptomic and chemical biology landscape for clear cell sarcoma. British Journal of Cancer, 128:1941-1954, Mar 2023. URL: https://doi.org/10.1038/s41416-023-02222-0, doi:10.1038/s41416-023-02222-0. This article has 4 citations and is from a domain leading peer-reviewed journal.

9. (bianco2024ewsr1atf1translocationa pages 12-13): Julia Raffaella Bianco, YiJing Li, Agota Petranyi, and Zsolt Fabian. Ewsr1::atf1 translocation: a common tumor driver of distinct human neoplasms. International Journal of Molecular Sciences, 25:13693, Dec 2024. URL: https://doi.org/10.3390/ijms252413693, doi:10.3390/ijms252413693. This article has 1 citations.

10. (NCT04274023 chunk 1): Study on TSR-042 in Advanced Clear Cell Sarcoma. Italian Sarcoma Group. 2024. ClinicalTrials.gov Identifier: NCT04274023

11. (cazzato2025clearcellsarcoma pages 8-10): Gerardo Cazzato, Francesco Piscazzi, Alessandra Filosa, Anna Colagrande, Paolo Del Fiore, Francesca Ambrogio, Chiara Battilotti, Andrea Danese, Serena Federico, and Fortunato Cassalia. Clear cell sarcoma (ccs) of the soft tissue: an update narrative review with emphasis on the utility of prame in differential diagnosis. Journal of Clinical Medicine, 14:1233, Feb 2025. URL: https://doi.org/10.3390/jcm14041233, doi:10.3390/jcm14041233. This article has 8 citations.

12. (NCT04593758 chunk 1): To Evaluate Maximally Tolerated Dose (MTD), Safety and Efficacy of CPI-613® (Devimistat) Plus Hydroxychloroquine in Patients With Relapsed or Refractory Clear Cell Sarcoma of Soft Tissue. Cornerstone Pharmaceuticals. 2021. ClinicalTrials.gov Identifier: NCT04593758

13. (NCT03132155 chunk 1): QUILT-3.031: AMG 337 in Subjects With Advanced or Metastatic Clear Cell Sarcoma. NantPharma, LLC. 2018. ClinicalTrials.gov Identifier: NCT03132155

14. (NCT04458922 chunk 1): Testing Atezolizumab in People 2-17 Years Old With Clear Cell Sarcoma or Advanced Chondrosarcoma. National Cancer Institute (NCI). 2020. ClinicalTrials.gov Identifier: NCT04458922

15. (NCT06942442 chunk 1): A Phase II Trial of Tebentafusp in HLA-A*02:01 Positive Patients With Advanced Clear Cell Sarcoma. Sarcoma Alliance for Research through Collaboration. 2025. ClinicalTrials.gov Identifier: NCT06942442

16. (NCT07153887 chunk 1): Vebreltinib for Advanced or Metastatic CCS. Second Affiliated Hospital, School of Medicine, Zhejiang University. 2025. ClinicalTrials.gov Identifier: NCT07153887