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NCT04757662

Tadalafil to Overcome Immunosuppression During Chemoradiotherapy for IDH-wildtype Grade III-IV Astrocytoma

Completed Phase 1 Last updated 13 June 2023
What this trial tests

Phase 1 trial testing Tadalafil in Grade III Astrocytoma in 18 participants. Completed in 7 June 2023.

Timeline
14 May 2021
Primary endpoint
7 June 2023
7 June 2023

Quick facts

Lead sponsorWashington University School of Medicine
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment18
Start date14 May 2021
Primary completion7 June 2023
Estimated completion7 June 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Washington University School of Medicine

Who can join

18 and older, any sex, with Grade III Astrocytoma or Grade IV Astrocytoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Increasing preclinical and clinical data have shown that myeloid-derived suppressor cells (MDSCs) may represent a significant driver of immunosuppression in glioblastoma (GBM, grade IV astrocytoma) and a potential mechanism of treatment resistance to chemoradiotherapy. Tadalafil, an FDA-approved drug with inexpensive cost and excellent safety profile, has been shown to effectively reduce MDSCs and restore T-cell activation in the peripheral blood and in the tumor microenvironment. The purpose of this study is to investigate the impact of targeting MDSCs in newly diagnosed IDH-wildtype grade III-IV astrocytoma by combining tadalafil with standard of care radiation therapy (RT) and temozolomide (TMZ).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion.
    Lu J, Luo Y, Rao D, Wang T, et al · · 2024 · cited 89× · PMID 38609997 · DOI 10.1186/s40164-024-00505-7
  2. Radiation-induced circulating myeloid-derived suppressor cells induce systemic lymphopenia after chemoradiotherapy in patients with glioblastoma.
    Ghosh S, Huang J, Inkman M, Zhang J, et al · · 2023 · cited 72× · PMID 36696484 · DOI 10.1126/scitranslmed.abn6758
  3. Tumor-Treating Fields in Glioblastomas: Past, Present, and Future.
    Guo X, Yang X, Wu J, Yang H, et al · · 2022 · cited 39× · PMID 35954334 · DOI 10.3390/cancers14153669
  4. Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes.
    Wang Y, Zhang T, Sun M, Ji X, et al · · 2021 · cited 26× · PMID 34680276 · DOI 10.3390/cancers13205127
  5. The multifaceted mechanisms of malignant glioblastoma progression and clinical implications.
    Sun R, Kim AH. · · 2022 · cited 21× · PMID 35920986 · DOI 10.1007/s10555-022-10051-5
  6. Modulation of T-cell function by myeloid-derived suppressor cells in hematological malignancies.
    Bhardwaj V, Ansell SM. · · 2023 · cited 20× · PMID 37091970 · DOI 10.3389/fcell.2023.1129343
  7. A pilot phase Ib study to evaluate tadalafil to overcome immunosuppression during chemoradiotherapy for IDH-wild-type glioblastoma.
    Ghosh S, Johanns TM, Chheda MG, Liu E, et al · · 2023 · cited 4× · PMID 37554225 · DOI 10.1093/noajnl/vdad088

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