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

Summary

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.

Timeline

Start

2018-11-13

Primary completion

2024-11-26

Completion

2024-11-26

Publications

• McNamara MG, Swain J, Craig Z, Sharma R, Faluyi O, Wadsley J, Morgan C, Wall LR, Chau I, Reed N, Sarker D, Margetts J, Krell D, Cave J, Sothi S, Anthoney A, Bell C, Patel A, Oughton JB, Cairns DA, Mansoor W, Lamarca A, Hubner RA, Valle JW. 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. EClinicalMedicine. 2023 Jun 2;60:102015. doi: 10.1016/j.eclinm.2023.102015. eCollection 2023 Jun.
• Craig Z, Swain J, Batman E, Wadsley J, Reed N, Faluyi O, Cave J, Sharma R, Chau I, Wall L, Lamarca A, Hubner R, Mansoor W, Sarker D, Meyer T, Cairns DA, Howard H, Valle JW, McNamara MG. NET-02 trial protocol: a multicentre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients with progressive poorly differentiated extrapulmonary neuroendocrine carcinoma (NEC). BMJ Open. 2020 Feb 5;10(2):e034527. doi: 10.1136/bmjopen-2019-034527.

Drugs

Indications