Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Vasodilator Agents

Urological Agents

Temozolomide

Tadalafil

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

* Tadalafil will be given orally once daily for a total of 60 days at a weight-normalized dose as follows:

  * 10 mg/day if weight ≤63.5 kg
  * 15 mg/day if weight \>63.5 kg and ≤104.3 kg
  * 20 mg/day for weight \>104.3 kg
* Standard of care fractionated radiation therapy (RT) to 60 Gy in 30 daily fractions will be administered in this study.
* Concurrent temozolomide (TMZ) will be administered as per standard of care, i.e., continuously (Monday through Sunday) from Day 1 of RT to the last day of RT at a daily oral dose of 75 mg/m\^2 at the discretion of treating medical oncologist.
* Adjuvant therapy will administered as per standard of care. Typically, this consists of adjuvant TMZ initiated 4 to 6 weeks after completion of RT for 6 cycles at 150-200 mg/m\^2 PO per day on Days 1-5 of every 28-day cycle. Tumor-treating fields or Optune device (Novocure) as per routine clinical care during adjuvant TMZ is permitted at the discretion of the treating physician.

Tadalafil is commercially available and will be purchased by the Siteman Cancer Center and distributed to participants free of charge.

Jiayi Huang, M.D.

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).

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

A Phase IB Study to Use Tadalafil to Overcome Immunosuppression During Chemoradiotherapy for IDH-wildtype Grade III-IV Astrocytoma

-Defined as grade 3-4 lymphopenia per CTCAE v5.0 (absolute lymphocyte count \< 500)

* PFS is defined as the time from enrollment in the trial until time of disease progression or death from any cause.
* Progression will measured per standard clinical care based on the Response Assessment in Neuro-Oncology (RANO) working group guideline

-OS is defined as the time from enrollment in the trial until the date of death due to any cause.

Washington University School of Medicine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Tadalafil to Overcome Immunosuppression During Chemoradiotherapy for IDH-wildtype Grade III-IV Astrocytoma	NCT04757662	Grade III Astro... Grade IV Astroc... Astrocytoma, Gr... Astrocytoma, Gr...	Tadalafil	18 Years -	Washington University School of Medicine
Tadalafil to Overcome Immunosuppression During Chemoradiotherapy for IDH-wildtype Grade III-IV Astrocytoma	NCT04757662	Grade III Astro... Grade IV Astroc... Astrocytoma, Gr... Astrocytoma, Gr...	Tadalafil	18 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for grade iii astrocytoma