Showing posts with label Th-227-PSMA. Show all posts
Showing posts with label Th-227-PSMA. Show all posts

Tuesday, August 11, 2020

PSMA-targeted radiopharmaceutical clinical trials in the US

Now that the VISION trial of Lu-177-PSMA-617 is no longer recruiting, some patients are wondering if they can still get PSMA-targeted radiopharmaceuticals in the US, without traveling to Germany, Australia, India, etc. Here is a list of trials that are active, still open to recruitment, or will soon be recruiting. 

Unless otherwise noted, they are all for men who are: 

  • metastatic
  • castration-resistant 
  • have had at least one taxane chemotherapy
  • at least one of the advanced androgen receptor therapies (e.g., Zytiga, Xtandi, Erleada, or Nubeqa)
  • no Xofigo
  • PSMA-avid on a PSMA PET/CT scan

Radiopharmaceutical

Adjuvant drugs

Extra criteria

Recruitment status/ contact

Locations

Lu-177-PSMA-617

 

Chemo and immunotherapy naïve, failed one hormonal

Recruiting

(Phase 3 RCT)

• Omaha, NE

• Spain

• France

Lu-177-PSMA-617


mHSPC

(M1 or N1)

Treatment naive

Recruiting

• Omaha, NE

• Spain

• France

Lu-177-PSMA-617

Keytruda

No chemo since castration resistant

recruiting

UCSF

Lu-177-CTT1403

 

No Jevtana

recruiting

UCSF

Lu-177-PSMA-617

 

 

recruiting

•Weill Cornell

•Tulane (not yet)

Th-227-Antibody

(see article)

 

 

recruiting

• Royal Marsden (UK)

• Finland

• Tulane

• MSK

• Omaha, NE

Lu-177-J591

Ketoconazole

Prior RP or RT

CRPC

Non-metastatic

recruiting

• Weill Cornell

• USC

• Georgetown

• IU

• U of Iowa

• UPMC

Lu-177-PSMA-R2

 

 

recruiting

• Stanford

• Yale

• Tulane

• Johns Hopkins

• Mt Sinai

• MD Anderson

• U of Wisconsin

• Phoenix

Ac-225-J591

 

 

recruiting

• Weill Cornell

• Brooklyn Methodist

Ac-225-J591 + Lu-177-PSMA- I&T

 

 

Begins June 2021

• Weill Cornell

• Brooklyn Methodist

Ac-225-J91

Keytruda

No chemo since castration resistant

Begins June 2021

• Weill Cornell

• Brooklyn Methodist

• Dana Farber

• Columbia

Cu-67-SAR-bisPSMA

 

Previous chemo OK, not required

Begins Sept 2021

• Johns Hopkins

•Mayo Rochester

•Mayo, AZ

•Tulane, N.O.

•Barnes Jewish, St. Louis

•Omaha, NE

•Weill Cornell

Lu-177-PSMA-617

(VISION)

 

 

Active, not recruiting

• 84 locations

Results expected August 2020

I-131-1095-MIPS

(see article)

Xtandi

Chemo naïve

Failed Zytiga

Active, not recruiting

• 17 locations

Results expected December 2021


Tuesday, October 30, 2018

Newest radiopharmaceutical: Th-227-PSMA-antibody

Bayer has announced a new clinical trial of the latest entry in the race for radiopharmaceuticals to treat prostate cancer, joining Lu-177-PSMA-617, Ac-225-PSMA-617, and I-131-MIP-1095. They are trying Thorium-227 attached to a PSMA antibody.

Thorium-227, like Ac-225, is an alpha-particle emitter. Alpha emitters are very powerful, but very short range, only killing cells that are 2 to 10 cells away from the cancer cell it attaches to. This may limit its toxicity, but may require higher doses for larger, more widespread tumors.  Beta emitters, like Lu-177, are less powerful, but the beta particle penetrates to a much greater depth, affecting about 125 cells. Researchers at the University of Heidelberg are experimenting with mixtures of the two.

The other part of the equation is the ligand that the radioactive atom is attached to and that attaches to the PSMA protein on the prostate cancer cell. Ligands include PSMA-617, PSMA-I&T, MIP-1095, and J591. Ligands may be small molecules, antibodies, or "minibodies." Bayer is using a proprietary antibody-type ligand that they developed for the purpose. Ligands that are more specific for PSMA have less toxicity.

On the other side of the ligand molecule, it must bind very tightly to the radioactive element. If it doesn't, the radioactive element might be released into systemic circulation where it can damage healthy cells. Heavy metals, like thorium, are attached relatively weakly by a process called "chelation," but some chelators are stronger than others. Researchers have so far been unsuccessful in developing a stable chelate for Ra-223 (the main ingredient in Xofigo, which is also manufactured by Bayer) to a PSMA ligand. However, Th-227 decays into Ra-223, so it is unknown if the thorium chelate will continue to hold as it decays. However, Bayer has already begun two clinical trials for Th-227 chelated to an antibody for non-Hodgkin's lymphoma since 2015, and for ovarian cancer and mesothelioma since April, which have not been terminated for excess toxicity. There is every reason to hope that the chelation complex they devised for the PSMA-antibody ligand holds up in biological systems. But if it doesn't hold chemically, it becomes the active ingredient in Xofigo, and may be doubly therapeutic in men with bone metastases.

This is a dose-finding (Phase 1) clinical trial among 108 patients with metastatic castration-resistant prostate cancer. They list 4 locations that will be recruiting: Memorial Sloan Kettering in NYC, Tulane (New Orleans), as well as locations in the UK and Finland.