Lu-DOTA-TATE + Chemotherapy + Immunotherapy for Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+21 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Novartis Pharmaceuticals

Must not be taking: Antibacterials, Antifungals, Antivirals, others

Disqualifiers: Autoimmune diseases, Severe infections, ECG abnormalities, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study aims to establish a safe and well tolerated dose of \[177Lu\]Lu-DOTA-TATE in combination with carboplatin, etoposide and atezolizumab in this setting and to assess preliminary efficacy of this combination treatment versus the combination of carboplatin, etoposide, and atezolizumab.The study will be essential to assess a new potential therapeutic option in participants with this aggressive cancer type.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have severe infections requiring treatment or are on certain immune therapies, you may need to stop those before joining.

What data supports the effectiveness of the drug Lu-DOTA-TATE for treating small cell lung cancer?

Research shows that Lu-DOTA-TATE, a radiolabeled somatostatin analog, has been effective in treating various neuroendocrine tumors, including small cell lung cancer, by targeting specific receptors on tumor cells. It has shown promising results in tumor regression and survival in animal models and has been used successfully in patients with other types of neuroendocrine tumors.

^{1 2 3 4 5}

Is Lu-DOTA-TATE safe for use in humans?

Lu-DOTA-TATE has been used as a treatment for neuroendocrine tumors, and studies have focused on its early efficacy and toxicity, indicating it has been evaluated for safety in humans. However, specific safety data for its use in combination with chemotherapy and immunotherapy for small cell lung cancer is not provided in the available research.

^{3 6 7 8 9}

What makes the Lu-DOTA-TATE + Chemotherapy + Immunotherapy treatment unique for small cell lung cancer?

This treatment is unique because it combines a radiopharmaceutical, [177Lu]Lu-DOTA-TATE, which targets somatostatin receptors on cancer cells, with chemotherapy and immunotherapy, potentially enhancing the overall effectiveness against small cell lung cancer. The use of [177Lu]Lu-DOTA-TATE is novel in this context, as it has primarily been used for neuroendocrine tumors, and its combination with other therapies could offer a new approach for this aggressive cancer type.

^{2 3 8 10 11}

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed ES-SCLC who haven't had treatment yet. They need a positive PET scan showing SSTR and at least one measurable tumor lesion. People can't join if they have brain metastasis, autoimmune diseases, severe infections, recent major surgery, ECG abnormalities that pose risks, known drug hypersensitivity or are in another clinical study.

Inclusion Criteria

I have at least one tumor that can be measured on a CT scan.

I am 18 years old or older.

I can provide a sample of my tumor for further testing.

Exclusion Criteria

You have an ongoing autoimmune disease or a history of autoimmune disease that could come back.

I do not have severe infections needing strong antibiotics or antivirals recently.

Concurrent participation in another therapeutic clinical study

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment - Induction

Participants receive [177Lu]Lu-DOTA-TATE in combination with carboplatin, etoposide, and atezolizumab

6 weeks

Weekly visits (in-person)

Treatment - Maintenance

Participants continue treatment with [177Lu]Lu-DOTA-TATE and atezolizumab

Variable, based on response

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Regular visits (in-person)

Participant Groups

The study tests the safety of [177Lu]Lu-DOTA-TATE combined with carboplatin, etoposide, and tislelizumab as initial treatment for ES-SCLC. It also looks at using tislelizumab alone as ongoing maintenance therapy after the first treatments.

Group I: Phase II Experimental arm Experimental Treatment 4 Interventions

\[177Lu\]Lu-DOTA-TATE at recommended dose declared in phase I part in combination with carboplatin, etoposide and atezolizumab (experimental arm)

Group II: Phase II Control arm Experimental Treatment 4 Interventions

Carboplatin, etoposide and atezolizumab alone (control arm)

Group III: Dose Level 4 (DL4) Experimental Treatment 5 Interventions

Dose Level 4 (DL4): \[177Lu\]Lu-DOTA-TATE 250 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.

Group IV: Dose Level 3b (DL3b) Experimental Treatment 5 Interventions

Dose Level 3b (DL3b): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 250 mCi plus atezolizumab 1200 mg in the maintenance period.

Group V: Dose Level 3a (DL3a) Experimental Treatment 5 Interventions

Dose Level 3a (DL3a): \[177Lu\]Lu-DOTA-TATE 200 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 mg in the maintenance period.

Group VI: Dose Level 2b (DL2b) Experimental Treatment 5 Interventions

Dose Level 2b (DL2b): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumad 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 200 mCi plus atezolizumab 1200 in the maintenance period.

Group VII: Dose Level 2a (DL2a) Experimental Treatment 5 Interventions

Dose Level 2a (DL2a): \[177Lu\]Lu-DOTA-TATE 150 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3 and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 150 mCi plus atezolizumab 1200 mg in the maintenance period.

Group VIII: Dose Level 1 (DL1) Experimental Treatment 5 Interventions

Dose Level 1 (DL1): \[177Lu\]Lu-DOTA-TATE 100 mCi with carboplatin AUC 5 D1, etoposide 100 mg/m2 D1-3, and atezolizumab 1200 mg in induction period, then \[177Lu\]Lu-DOTA-TATE 100 mCi plus atezolizumab 1200 mg in the maintenance period.

[177Lu]Lu-DOTA-TATE 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
• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in children aged 12 years and older

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University Hospitals of Cleveland Cleveland, OH

University Cancer and Blood Center LLC Athens, GA

Hackensack Meridian Health Edison, NJ

Fox Chase Cancer Center Philadelphia, PA

More Trial Locations

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. [2013] Therapy using the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) has been used primarily in gastroenteropancreatic neuroendocrine tumors. Here we present the effects of this therapy in a small number of patients with metastasized or inoperable paragangliomas, meningiomas, small cell lung carcinomas (SCLCs), and melanomas.

2. Germany pubmed.ncbi.nlm.nih.gov

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. [2020] Label="PURPOSE">Therapy with [177Lu-DOTA,Tyr3]octreotate is effective in patients with grade I/II metastasized and/or inoperable bronchial neuroendocrine tumour (NET) or gastroenteropancreatic NET (GEP-NET). In this study, we investigated the efficacy and safety of salvage treatment with [177Lu-DOTA,Tyr3]octreotate.

3. United States pubmed.ncbi.nlm.nih.gov

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.

4. United States pubmed.ncbi.nlm.nih.gov

Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. [2022] Regular therapy with the radiolabeled somatostatin analog (177)Lu-octreotate (22.2-29.6 GBq) in patients with gastroenteropancreatic or bronchial neuroendocrine tumors results in tumor remission in 46% of patients, including minor response. We present the effects of additional therapy with (177)Lu-octreotate in patients in whom progressive disease developed after an initial benefit from regular therapy.

5. Germany pubmed.ncbi.nlm.nih.gov

[177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. [2022] The somatostatin analogue [DOTA0,Tyr3]octreotate has a nine-fold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0, Tyr3]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide lutetium-177, this compound has been shown to have a very favourable impact on tumour regression and animal survival in a rat model. Because of these reported advantages over the analogues currently used for somatostatin receptor-mediated radiotherapy, we decided to compare [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) with [111In-DTPA0]octreotide (111In-octreotide) in six patients with somatostatin receptor-positive tumours. Plasma radioactivity after 177Lu-octreotate expressed as a percentage of the injected dose was comparable with that after 111In-octreotide. Urinary excretion of radioactivity was significantly lower than after 111In-octreotide, averaging 64% after 24 h. The uptake after 24 h, expressed as a percentage of the injected dose of 177Lu-octreotate, was comparable to that after 111In-octreotide for kidneys, spleen and liver, but was three- to fourfold higher for four of five tumours. The spleen and kidneys received the highest absorbed doses. The doses to the kidneys were reduced by a mean of 47% after co-infusion of amino acids. It is concluded that in comparison with the radionuclide-coupled somatostatin analogues that are currently available for somatostatin receptor-mediated radiotherapy, 177Lu-octreotate potentially represents an important improvement. Higher absorbed doses can be achieved to most tumours, with about equal doses to potentially dose-limiting organs; furthermore, the lower tissue penetration range of 177Lu as compared with 90Y may be especially important for small tumours.

6. England pubmed.ncbi.nlm.nih.gov

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.

7. Germany pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND">The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE.

8. Netherlands pubmed.ncbi.nlm.nih.gov

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations. [2021] Lutetium-177 [177Lu] tetra-azacyclododecanetetra-acetic acid [DOTA]-(Tyr3)-octreotate [TATE] ([177Lu]Lu-DOTA-TATE) is a radiopeptide used for peptide receptor radionuclide therapy in patients with neuroendocrine tumours (NETs). This radiopeptide is made by labelling the ligand octreotate with Lutetium-177 using the linker DOTA. After labelling, and before clinical application quality control of the radiopeptide is needed and the radiochemical purity is assessed. Acceptance limits for radiochemical purity should be within 90-110% of the label claim for radiopharmaceuticals for diagnostic use and within 95-105% of the label claim for radiopharmaceuticals for therapeutic use. Moreover, the amount of unlabelled [177Lu]LuCl3 cannot exceed 2% of the radioactive dose. Since no monograph is available for [177Lu]Lu-DOTA-TATE in the European Pharmacopeia (Ph Eur), this article describes the development and validation of a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection and radiodetection. A Waters Acquity Arc UHPLC system equipped with a Waters 2998 photodiode array (PDA) detector was used coupled to a Berthold Lb 514 Flowstar detector equipped with a BGO-X gamma measuring cell. A reversed phase Symmetry Shield C18 column (4.6 mm × 250 mm, 5 µm) was used for chromatographic separation. A flow of 1.5 mL/min was maintained during analysis, using 0.1% TFA in water as mobile phase A and 0.1% TFA in ACN as mobile phase B. The retention time was around 1.7 min and 13.5 min for [177Lu]LuCl3 and [177Lu]Lu-HA-DOTA-TATE, respectively. Stock solutions of [177Lu]LuCl3 were made by serial dilution and were injected to test for linearity, accuracy and precision, carry over and signal-to-noise ratio. A [177Lu]Lu-HA-DOTA-TATE sample was prepared and injected to determine the carry over. The results showed that the method is linear over a range of 0.300-130 MBq/mL, which covers the range for clinical samples, provided that the clinical sample is diluted ten times before analysis. The LLOQ can be measured accurately even after dilution, with a signal-to-noise ratio of at least 5. In short, the method is accurate, precise and sensitive and can be implemented as part of the quality control of [177Lu]Lu-HA-DOTA-TATE.

9. England pubmed.ncbi.nlm.nih.gov

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.

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay. [2019] Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear properties. In this paper we describe the development and evaluation in Uruguay of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation of these 177Lu radiopharmaceuticals including radiolabelling, quality control methods, in vitro and in vivo stability and their therapeutic application in patients. Radiation dosimetry aspects of 177Lu are also included. Nine male patients with prostate cancer and four female patients with breast carcinoma with multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2 GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu-EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days post administration. Images allow skeletal visualization with high definition and demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial remissions were obtained in 4 patients and the remaining patient did not show significant progression 3 months after the second cycle. No serious adverse effects were registered, even in two patients with confirmed renal disease and high risk for renal disease Dosimetry assessments confirm the predictive value of the personalized therapy with radiolabelled peptides. We found it is possible to accumulate high therapeutic doses in tumours in sequential administrations of 177Lu-DOTA-TATE, increasing the probability of biological response without significant impairment of the renal function in patients with risk factors. These results demonstrate the attractive therapeutic properties of these two 177Lu labelled agents and the feasibility of this metabolic therapy in regions far away from 177Lu producing countries.

11. United States pubmed.ncbi.nlm.nih.gov

Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. [2018] Label="INTRODUCTION" NlmCategory="BACKGROUND"> 177Lu-DOTA-TATE is a clinically useful and promising therapeutic radiopharmaceutical for peptide receptor radionuclide therapy of neuroendocrine tumors (NETs) overexpressing somatostatin receptors. Currently, the radiopharmaceutical is prepared in-house at nuclear medicine centers, thereby restricting its use to limited centers only. In this article, the authors describe systematic studies toward bulk scale formulation of "ready-to-use" 177Lu-DOTA-TATE using medium specific activity 177Lu (740-1110 GBq/mg) at a centralized radiopharmacy facility.