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Ronny Allan
PARP inhibitor with PRRT clinical trials update.
1. NIH Trial Summary
A phase I/II clinical trial at the NIH Clinical Center evaluates the effectiveness of a combination of two agents that may work in complementary ways to target inoperable or metastatic neuroendocrine tumoors. One agent, lutathera, emits radiation inside the body, causing DNA damage, and the second agent, olaparib, a PARP inhibitor, blocks the repair of DNA breaks. The trial commences in Oct 2022 running for approximately 2 years 9 months.
What is Lutathera?
It’s a type of Peptide Receptor Radionuclide Therapy (PRRT) and has been in use for some years as a standard of care (mostly second line). Read more click here.
What is Olaparib and what does it do in conjunction with Lutathera?
Olaparib (AZD-2281, trade name Lynparza) is an FDA-approved targeted therapy for cancer, developed by KuDOS Pharmaceuticals and later by AstraZeneca. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair.
Once injected, Lutathera circulates throughout the body and targets the radiation specifically to these neuroendocrine tumour cells, including tumours that might not even be visible on CT scans and other imaging. This focused radiation kills tumour cells by damaging their DNA, and Olaparib is expected to further its effectiveness by preventing the tumour cells from repairing their DNA, i.e. inhibition of PARP results in an antineoplastic effect.
2. Australian Trial Summary
This phase 1, single arm, single centre study at PeterMac Melbourne is designed to evaluate the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate in patients with metastatic NET (PARLuNET (protocol number 20/163)). It is hoped that of a combination of two agents that may work in complementary ways to target inoperable or metastatic neuroendocrine tumours. One agent, lutathera, emits radiation inside the body, causing DNA damage, and the second agent, talazoparib, a PARP inhibitor, blocks the repair of DNA breaks. The trial commences December 2021 and runs for approximately 4 years.
What is Lutathera?
It’s a type of Peptide Receptor Radionuclide Therapy (PRRT) and has been in use for some years as a standard of care (mostly second line). Read more click here.
What is Talazoparib and what does it do in conjunction with Lutathera?
Talazoparib is a poly-ADP ribose polymerase inhibitor used to treat HER2-, BRCA mutated locally advanced or metastatic breast cancer. (BNM-673, trade name Talzenna) is approved by FDA/UK NHS and many other countries as a targeted therapy for certain cancers, developed by Pfizer. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair.
Once injected, Lutathera circulates throughout the body and targets the radiation specifically to these neuroendocrine tumour cells, including tumours that might not even be visible on CT scans and other imaging. This focused radiation kills tumour cells by damaging their DNA, and PARP inhibitor is expected to further its effectiveness by preventing the tumour cells from repairing their DNA, i.e. inhibition of PARP results in an antineoplastic effect.
Why are these trials important?
The first thing that struck me was the term inoperable in one of the trial names. This gives an additional option for those with inoperable tumours (including metastases). While it is already an option for inoperable patients, the added punch of a PARP inhibitor gives them a better chance of reducing tumour cells.
Secondly, if PARP is seen to improve the efficiency of PRRT generally, that is of benefit to all those prescribed this therapy, regardless of inoperable status.
Read more here
1. NIH ClinicalTrials.gov Identifier: NCT04086485
2. NCI Summary for the NIH trial: Read here (with apologies for old nomenclature, disappointing really in my opinion)
3. Australian ClinicalTrials.gov Identifier: NCT05053854
4. Article discussion the Australian trial: Read here.
General Clinical Trials Disclaimer
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net
The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.
Disclaimer
I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional as they are not members of the private group or followers of my sites in any official capacity. Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.
Finally
Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product. Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET
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Hi Ronny,
This trial seems similar to the PARLuNET (protocol number 20/163) being run by Peter MacCallum Cancer Centre (A/Prof Grace Kong) in Melbourne, not sure if you’ve written about that. I was offered a place in the trial but as I hadn’t had any PRRT at that stage, I went for the ‘standard’ offering here, which is LuTate with Capecitebane.
I think it’s the follow up standard to this one ? Will check the other
https://ronnyallan.net/2016/05/20/prrt-and-chemo-combination-therapy-on-trial/
I updated this article to cover both trials – many thanks for the tip