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

Sponsor
The Christie NHS Foundation Trust
Study ID
NCT03837977
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Liposomal Irinotecan — DRUG
    Arm I
  • Fluorouracil — DRUG
    Arm I
  • Folinic Acid — DRUG
    Arm I
  • Docetaxel — DRUG
    Arm II

Study Details

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.

Key Dates

Start date
Nov 13, 2018
Status verified
Dec 2024
Primary completion
Nov 26, 2024
Completion
Nov 26, 2024

Study Design

Enrollment
58 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: nal-IRI, 5-FU and racemic folinic acid
    liposomal Irinotecan (naI-IRI) (80mg/m\*2 intravenously over 90 minutes (± 10 minutes) prior to Fluorouracil (5-FU) 5-FU 2400 mg /m\*2 BSA infusor over 46 hours racemic folinic acid (as per local standard practice) every 14 days
  • Active Comparator: docetaxel
    75mg/m\*2 intravenously over 60 minutes) every 21 days\]

Primary Outcome Measure

Progression-free survival defined as a binary outcome (progression-free or not) [ Time Frame: treatment start date until 6 months, assessed at 8 weekly intervals by CT scan ]

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