NCT03837977: NET02

Second-line Therapy for Patients With Progressive Poorly Differentiated Extra-pulmonary Neuroendocrine Carcinoma

Completed Phase 2 Last updated 30 December 2024

What this trial tests

Phase 2 trial testing Liposomal Irinotecan in Oncology in 58 participants. Completed in 26 November 2024.

Timeline

13 November 2018

Primary endpoint
26 November 2024

26 November 2024

Quick facts

Lead sponsor	The Christie NHS Foundation Trust
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	58
Start date	13 November 2018
Primary completion	26 November 2024
Estimated completion	26 November 2024
Sites	4 locations across United Kingdom

Drugs / interventions tested

• Liposomal Irinotecan
• Fluorouracil — full drug profile →
• Folinic Acid — full drug profile →
• Docetaxel (Docetaxel) — full drug profile →

Conditions studied

• Oncology — all drugs for Oncology →
• Neuroendocrine Carcinoma — all drugs for Neuroendocrine Carcinoma →

Sponsor

The Christie NHS Foundation Trust

Who can join

18 and older, any sex, with Oncology or Neuroendocrine Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

There is currently no standard treatment beyond first-line etoposide/platinum-based chemotherapy in patients with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma. Therefore the treatment of patients whose disease progresses on or after this first-line treatment is an area of unmet need.

Combination regimens such as irinotecan/5-fluorouracil/folinic acid are a second-line treatment option currently used in Europe and world-wide for this subset of patients. However, there is currently no trial evidence supporting this treatment regimen in these patients.

Results of the NAPOLI-1 phase III trial of liposomal irinotecan in the treatment of patients with metastatic pancreatic adenocarcinoma after gemcitabine-based therapy reported improved survival for those patients who received a combination of liposomal irinotecan with 5-FU/folinic acid compared to those patients who received 5-FU/folinic acid alone. Liposomal irinotecan has been found to show an improved distribution into tumour tissue in comparison to irinotecan, and this may have clinical benefit in patients with extra-pulmonary neuroendocrine carcinoma.

Docetaxel is standardly used as a second-line treatment option in patients with small cell lung cancer who have progressed on primary etoposide-platinum combination therapy. Therefore this drug could also have clinical benefit in patients with extra-pulmonary neuroendocrine carcinoma as the biology of the disease is similar to small cell lung cancer.

The overall aim of the NET-02 trial is to select a treatment for continuation to a Phase III trial. The intention of the trial is to determine whether liposomal irinotecan/5-fluorouracil/folinic acid and docetaxel are sufficiently active in this population of patients. If both treatments are found to be efficacious, selection criteria will be applied to select a treatment to take forward.

102 eligible participants will be randomised to receive either liposomal irinotecan/5-fluorouracil/folinic acid given every 14 days, or docetaxel given every 21 days. Participants will be treated for a minimum of 6 months or until discontinuation of treatment as per protocol.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. PEGylated therapeutics in the clinic.
   Gao Y, Joshi M, Zhao Z, Mitragotri S. · · 2024 · cited 133× · PMID 38193121 · DOI 10.1002/btm2.10600
2. Lipid-based nanoparticles as drug delivery carriers for cancer therapy.
   Waheed I, Ali A, Tabassum H, Khatoon N, et al · · 2024 · cited 65× · PMID 38660132 · DOI 10.3389/fonc.2024.1296091
3. Clinical considerations for the management of androgen indifferent prostate cancer.
   Berchuck JE, Viscuse PV, Beltran H, Aparicio A. · · 2021 · cited 46× · PMID 33568748 · DOI 10.1038/s41391-021-00332-5
4. Expanding Therapeutic Opportunities for Extrapulmonary Neuroendocrine Carcinoma.
   Frizziero M, Kilgour E, Simpson KL, Rothwell DG, et al · · 2022 · cited 30× · PMID 35091446 · DOI 10.1158/1078-0432.ccr-21-3058
5. Second-line treatment in patients with advanced extra-pulmonary poorly differentiated neuroendocrine carcinoma: a systematic review and meta-analysis.
   McNamara MG, Frizziero M, Jacobs T, Lamarca A, et al · · 2020 · cited 30× · PMID 32426044 · DOI 10.1177/1758835920915299
6. Chemotherapy in NEN: still has a role?
   Espinosa-Olarte P, La Salvia A, Riesco-Martinez MC, Anton-Pascual B, et al · · 2021 · cited 25× · PMID 33843007 · DOI 10.1007/s11154-021-09638-0
7. Systemic Treatment of Gastroenteropancreatic Neuroendocrine Carcinoma.
   Mollazadegan K, Welin S, Crona J. · · 2021 · cited 21× · PMID 34110508 · DOI 10.1007/s11864-021-00866-9
8. NET-02: a randomised, non-comparative, phase II trial of nal-IRI/5-FU or docetaxel as second-line therapy in patients with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma.
   McNamara MG, Swain J, Craig Z, Sharma R, et al · · 2023 · cited 13× · PMID 37287870 · DOI 10.1016/j.eclinm.2023.102015