CompletedPhase 2

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

United Kingdom58 participantsStarted 2018-11-13

Plain-language 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.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Age ≥18 years and life expectancy ≥3 months.
✓. Diagnosed with poorly differentiated (as defined by the World Health Organisation in 2010, Ki 67 ≥20%) extra-pulmonary neuroendocrine carcinoma (NEC grade 3, confirmed by histology). (Carcinoma of unknown primary is allowed if lung primary has been excluded following review by the multi-disciplinary team).
✓. Prior treatment with first-line platinum-based chemotherapy for NEC in the advanced setting and ≥28 days from Day 1 of the previous treatment cycle.
✓. Documented radiological evidence of disease progression OR discontinuation of first-line platinum-based chemotherapy due to intolerance.
✓. Measurable disease according to RECIST 1.1
✓. Eastern Co-operative Oncology Group (ECOG) performance status ≤2
✓. Adequate renal function with serum creatinine ≤1.5 times upper limit of normal (ULN) and creatinine clearance ≥50ml30ml/min according to Cockroft-Gault or Wright formula. If the calculated creatinine clearance is less than 30 ml/min, glomerular filtration rate (GFR) may be assessed using either Cr51-EDTA or 99mTc-DTPA clearance method to confirm if GFR is ≥30 ml/min).
✓. Adequate haematological function: Hb ≥90g/L, WBC ≥3.0 x 109/L, ANC ≥1.5 x 109/L, platelet count ≥100 x 109/L.

What they're measuring

Progression-free survival defined as a binary outcome (progression-free or not)

Timeframe: treatment start date until 6 months, assessed at 8 weekly intervals by CT scan

Trial details

NCT IDNCT03837977

SponsorThe Christie NHS Foundation Trust

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-11-26

View on ClinicalTrials.gov More Oncology trials

Plain-language summary

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Age ≥18 years and life expectancy ≥3 months.
✓. Diagnosed with poorly differentiated (as defined by the World Health Organisation in 2010, Ki 67 ≥20%) extra-pulmonary neuroendocrine carcinoma (NEC grade 3, confirmed by histology). (Carcinoma of unknown primary is allowed if lung primary has been excluded following review by the multi-disciplinary team).
✓. Prior treatment with first-line platinum-based chemotherapy for NEC in the advanced setting and ≥28 days from Day 1 of the previous treatment cycle.
✓. Documented radiological evidence of disease progression OR discontinuation of first-line platinum-based chemotherapy due to intolerance.
✓. Measurable disease according to RECIST 1.1
✓. Eastern Co-operative Oncology Group (ECOG) performance status ≤2
✓. Adequate renal function with serum creatinine ≤1.5 times upper limit of normal (ULN) and creatinine clearance ≥50ml30ml/min according to Cockroft-Gault or Wright formula. If the calculated creatinine clearance is less than 30 ml/min, glomerular filtration rate (GFR) may be assessed using either Cr51-EDTA or 99mTc-DTPA clearance method to confirm if GFR is ≥30 ml/min).
✓. Adequate haematological function: Hb ≥90g/L, WBC ≥3.0 x 109/L, ANC ≥1.5 x 109/L, platelet count ≥100 x 109/L.

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Exclusion criteria