Lutathera + Olaparib for Neuroendocrine Cancer
Recruiting in Palo Alto (17 mi)
Overseen ByFrank I Lin, M.D.
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Trial Summary
What is the purpose of this trial?Background:
A neuroendocrine tumor is a rare type of tumor. It comes from body cells called neuroendocrine cells. Sometimes, these tumors develop in the gastrointestinal tract and pancreas. Researchers want to find out if a combination of drugs can shrink these tumors.
Objective:
To learn if people with certain neuroendocrine tumors can take a combination of 2 drugs, Lutathera and Olaparib, without having severe side effects, and if this treatment makes the tumors shrink.
Eligibility:
Adults 18 and older who have a neuroendocrine tumor in the pancreas or intestine that cannot be cured by surgery and has somatostatin receptors on the cells.
Design:
Eligible participants will get Lutathera through an intravenous (IV) infusion every 8 weeks for 4 cycles. One cycle is 8 weeks. Each cycle includes a follow-up visit at week 4. For the IV, a small plastic tube is put into an arm vein.
Participants will also take Olaparib by mouth twice a day for 4 weeks of each cycle. They will use a medicine diary to track the doses.
During the study, participants will have physical exams. They will have blood and urine tests. They will fill out questionnaires about their general well-being and function. Their heart function will be tested. They will have scans of their chest, abdomen, and pelvis. One type of scan will use an IV infusion of a radioactive tracer.
Participants will have a follow-up visit about 4 weeks after treatment ends. Then they will have follow-up visits every 12 weeks for 3 years. Then they will have yearly phone calls.
What makes the Lutathera + Olaparib treatment unique for neuroendocrine cancer?
Lutathera (Lu-177-DOTATATE) is a novel treatment for neuroendocrine tumors that targets somatostatin receptors, which are often present on these tumors, using a radioactive substance to deliver targeted radiation. This approach is unique because it combines targeted therapy with radiation, offering a new option for patients with limited treatment choices.
127910Is Lutathera (Lu-177-DOTATATE) generally safe for humans?
Lutathera (Lu-177-DOTATATE) is generally considered safe for humans, with side effects that are usually mild and reversible. Severe long-term side effects are rare, and most patients experience an improved quality of life.
12467What data supports the effectiveness of the treatment Lutathera + Olaparib for neuroendocrine cancer?
Research shows that Lutathera (a form of Lutetium-177-DOTATATE) is effective in treating neuroendocrine tumors, with significant tumor regression and improved quality of life. Patients treated with Lutathera have a median progression-free survival of over 40 months and a longer overall survival compared to other treatments.
23578Will I have to stop taking my current medications?
The trial does not specify if you need to stop all current medications, but it does mention that you cannot use certain medications like strong CYP3A inhibitors or inducers close to the start of the trial. If you are on somatostatin analogue therapy, you must have been on a consistent dose for at least 3 months before joining the study.
Eligibility Criteria
Adults over 18 with inoperable neuroendocrine tumors in the pancreas or intestine, which have somatostatin receptors and haven't been cured by surgery. Participants must not be pregnant, agree to use contraception, and should not have had certain previous cancer treatments or uncontrolled illnesses.Inclusion Criteria
I am fully active and can carry on all my pre-disease activities without restriction.
I have been on a stable dose of somatostatin analogue therapy for at least 3 months.
I am 18 years old or older.
My organ and bone marrow functions are normal.
I have been diagnosed with a neuroendocrine tumor.
My condition cannot be treated with surgery due to its advanced stage.
Exclusion Criteria
I do not have any unmanaged ongoing illnesses.
I have brain metastases that are causing symptoms and are not under control.
I have been treated with PARP inhibitors or radionuclide agents before.
I have lasting side effects from cancer treatment that are moderate or worse.
I have been treated with Lu-177-DOTATATE before.
My spinal cord compression has been definitively treated.
I have an active hepatitis B or C infection.
I have had a stem cell or bone marrow transplant from a donor.
I cannot take medicine by mouth.
I have not had major surgery in the last 4 weeks.
I have been diagnosed with a blood disorder that could be or is turning into leukemia.
Participant Groups
The trial is testing if Lutathera (given via IV every 8 weeks for four cycles) combined with Olaparib (taken orally twice daily for four weeks each cycle) can safely shrink gastroenteropancreatic neuroendocrine tumors without causing severe side effects.
2Treatment groups
Experimental Treatment
Group I: 2/Lu-177-DOTATATE + Olaparib fixed doseExperimental Treatment5 Interventions
Lu-177-DOTATATE and olaparib at the MTD
Group II: 1/Lu-177-DOTATATE + Olaparib escalationExperimental Treatment5 Interventions
Lu-177-DOTATATE and escalating doses of olaparib to determine the maximum-tolerated dose (MTD)
Lu-177-DOTATATE is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Lutathera for:
- Unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults
🇺🇸 Approved in United States as Lutathera for:
- Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults and children aged 12 years and older
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model. [2019](177)Lu-DOTA-Tyr(3)-octreotate is a candidate radiopharmaceutical for the therapy of somatostatin receptor (sstr)-positive small cell lung cancer (SCLC). Scintigraphy of lung tumors is made with 2 alternative somatostatin analogs, (111)In-DTPA-octreotide or (99m)Tc-depreotide. The aim of this study was to compare the biodistribution of these 3 radiopharmaceuticals in SCLC xenografted to nude mice.
Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT? [2019]Patients with somatostatin receptor subtype 2-positive metastasised neuroendocrine tumours can be treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate. Some use octreotide as the peptide for peptide receptor radionuclide therapy (PRRT). We compared in seven patients [(177)Lu-DOTA(0),Tyr(3)]octreotide ((177)Lu-DOTATOC) and [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE), to see which peptide should be preferred for PRRT with (177)Lu.
Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. [2022]Treatment with the radiolabelled somatostatin analogue (177)Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to (177)Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination.
[Radionuclide therapy for neuroendocrine tumours]. [2019]Peptide receptor radionuclide therapy using somatostatin analogues labelled with beta-emitting isotopes can be given to patients with metastasized or inoperable neuroendocrine tumours provided these have increased uptake on octreotide scintigraphy. This is a brief review of the treatment principle, indications and contraindications and practices with (177)Lu-DOTATATE treatment used at Rigshospitalet. Side effects are generally mild and reversible. Severe long-term side effects are rare. The majority of patients will experience increased quality of life and partial tumour reduction or stabilization for a period of time. However, up to 20% will experience no treatment effect.
Lutetium-labelled peptides for therapy of neuroendocrine tumours. [2022]Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with (177)Lu-DOTATATE as well as the limited side effects with additional cycles of (177)Lu-DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours.
Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. [2019]The clinical applications of radiolabeled somatostatin analogue (177) Lu-DOTA-Tyr(3) -Thr(8) -Octreotide ((177) Lu-DOTATATE) constitute a promising treatment option for patients with disseminated and inoperable neuroendocrine (NET) tumors. Formulation of (177) Lu-DOTATATE in hospital radiopharmacy under aseptic conditions in a safe and reliable manner is a major constraint for its extensive use. The present work was intended to develop a kit for the safe preparation of the therapeutic radiopharmaceutical, viz. (177) Lu-DOTATATE of high quality that can be easily adapted at conventional hospital radiopharmacies. Single vial kits of DOTATATE were formulated and evaluated for suitability for radiolabeling as well as stability on its storage. Patient dose of (177) Lu-DOTATATE (7.4 GBq) could be successfully prepared using semi-automated in-house setup that assures safe handling and high yields of product of pharmaceutical purity suitable for clinical use. Fast clearance of activity via renal route was observed in preclinical biodistribution studies of (177) Lu-DOTATATE carried out in normal Swiss mice. Deployment of in-house produced (177) LuCl3 , cold kits and easy adaptability of synthesis setup at hospital radiopharmacy for preparation is likely to expand applications of peptide receptor radionuclide therapy.
Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]Lutetium-177 DOTA-D-Phe1-Tyr3-octreotide (Lu-DOTATATE) is a treatment option for patients with well-differentiated metastatic neuroendocrine tumours. Our centre started administering this therapy in 2012. The aim of this study was therefore to analyse the first cohort of patients treated with Lu-DOTATATE to determine its early efficacy and toxicity.
Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. [2023]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Somatostatin receptor-positive neuroendocrine tumors have been targeted using various peptide analogs radiolabeled with therapeutic radionuclides for years. The better biomedical properties of radioantagonists as higher tumor uptake make these radioligands more attractive than agonists for somatostatin receptor-targeted radionuclide therapy. In this study, we tried to evaluate the efficiency of Luthetium-177 (177Lu) radiolabeled DOTA-Peptide 2 (177Lu-DOTA-Peptide 2) as a new radioantagonist in HT-29 human colorectal cancer in vitro and in vivo.
[68Ga-DOTATOC PET/CT for Diagnosing Neuroendocrine Tumors]. [2022]Lutathera is a peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors and was approved as the first PRRT drug in Japan in 2021. Although neuroendocrine tumors are often less aggressive than other highly malignant and invasive tumors, there have been few effective therapy options, so "Lutathera"is a long-awaited treatment. Lutathera is indicated for the treatment of "somatostatin receptor-positive neuroendocrine tumors". Currently, in Japan, the only imaging method to evaluate the expression of somatostatin receptors in lesions is scintigraphy using In-111 pentetreotide(OctreoScan). In this section, we would like to introduce the current status of the 68Ga-DOTA-SSA PET/CT using somatostatin analogue(SSA)in our institution.
177Lu-Dotatate administration using an infusion pump or a peristaltic pump: comparison of two methods. [2022]Label="OBJECTIVES" NlmCategory="OBJECTIVE"> 177Lu-oxodotreotide (Lutathera) is an intravenous peptide receptor radionuclide therapy to treat unresectable metastatic digestive neuroendocrine tumours. The recommended method for Lutathera administration is gravity infusion; however, other appropriate and safe techniques are possible. This work compares two infusion methods from a medico-economic, radiation protection, efficiency and practicality point of view.