~116 spots leftby Mar 2029

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

Recruiting at 21 trial 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.12345

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.36789

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.2381011

Research Team

NP

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

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.
See 5 more

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
See 5 more

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)

Treatment Details

Interventions

  • [177Lu]Lu-DOTA-TATE (Radioisotope Therapy)
  • Carboplatin (Alkylating agents)
  • Etoposide (Topoisomerase I inhibitors)
  • Tislelizumab (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
8Treatment groups
Experimental Treatment
Group I: Phase II Experimental armExperimental Treatment4 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 armExperimental Treatment4 Interventions
Carboplatin, etoposide and atezolizumab alone (control arm)
Group III: Dose Level 4 (DL4)Experimental Treatment5 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 Treatment5 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 Treatment5 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 Treatment5 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 Treatment5 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 Treatment5 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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials
2,963
Recruited
4,275,000+
Founded
1996
Headquarters
Basel, Switzerland
Known For
Precision medicine
Top Products
Gleevec, Cosentyx, Entresto, Kisqali
Dr. Vas Narasimhan profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

177Lu-octreotate therapy showed potential effectiveness in treating paragangliomas and meningiomas, with some patients experiencing tumor regression or stable disease, although response rates were lower than in gastroenteropancreatic neuroendocrine tumors.
The treatment did not demonstrate any antitumor effects in patients with small cell lung carcinoma or melanoma, highlighting the need for further studies to confirm these findings due to the small patient sample size.
Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma.van Essen, M., Krenning, EP., Kooij, PP., et al.[2013]
Salvage treatment with [177Lu-DOTA,Tyr3]octreotate is effective and safe for patients with progressive bronchial neuroendocrine tumors (NET) or gastroenteropancreatic NET (GEP-NET), showing a median overall survival of 80.8 months after initial treatment.
The treatment resulted in low rates of severe side effects, with only 6.6% and 7.7% of patients experiencing grade III/IV bone marrow toxicity after re-treatment and re-re-treatment, respectively, and no cases of severe kidney toxicity were reported.
Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours.van der Zwan, WA., Brabander, T., Kam, BLR., et al.[2020]
(177)Lu-DOTA-Tyr(3)-octreotate demonstrated the highest tumor uptake in small cell lung cancer (SCLC) models, indicating its potential as an effective therapeutic option compared to other radiopharmaceuticals.
(111)In-DTPA-octreotide showed better tumor localization than (99m)Tc-depreotide, suggesting that (111)In-DTPA-octreotide may be more effective for detecting SCLC due to its higher tumor-to-normal tissue activity concentration ratios.
Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model.Schmitt, A., Bernhardt, P., Nilsson, O., et al.[2019]

References

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. [2013]
Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. [2020]
Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model. [2019]
Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. [2022]
[177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. [2022]
Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]
Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023]
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]
Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. [2019]
10.United Arab Emiratespubmed.ncbi.nlm.nih.gov
¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects. [2018]