NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma

Abstract

BackgroundBoth oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal adenocarcinoma, but no randomised study has compared their efficacy and toxicity. This randomised phase II “pick a winner” trial will identify the optimum regimen to take forward to a future phase III trial against neo-adjuvant chemotherapy, the current standard in the UK.Methods/DesignPatients with resectable adenocarcinoma of the oesophagus or Siewert Type 1–2 gastro-oesophageal junction (GOJ), ≥T3 and/or ≥ N1 are eligible for the study. Following two cycles of induction OXCAP chemotherapy (oxaliplatin 130 mg/m2 D1, Cape 625 mg/m2 D1-21, q 3 wk), patients are randomised 1:1 to OXCAP-RT (oxaliplatin 85 mg/m2 Day 1,15,29; capecitabine 625 mg/m2 twice daily on days of RT; RT-45 Gy/25 fractions/5 weeks) or CarPac-RT (Carboplatin AUC2 and paclitaxel 50 mg/m2 Day 1,8,15,22,29; RT-45 Gy/25 fractions/5 weeks). Restaging CT/PET-CT is performed 4–6 weeks after CRT, and a two-phase oesophagectomy with two-field lymphadenectomy is performed six to eight weeks after CRT. The primary end-point is pathological complete response rate (pCR) at resection and will include central review. Secondary endpoints include: recruitment rate, toxicity, 30-day surgical morbidity/mortality, resection margin positivity rate and overall survival (median, 3- and 5-yr OS. 76 patients (38/arm) gives 90% power and one-sided type 1 error of 10% if patients on one novel treatment have a response rate of 35% while the second treatment has a response rate of 15%. A detailed RT Quality Assurance (RTQA) programme includes a detailed RT protocol and guidance document, pre-accrual RT workshop, outlining exercise, and central evaluation of contouring and planning. This trial has been funded by Cancer Research UK (C44694/A14614), sponsored by Velindre NHS Trust and conducted through the Wales Cancer Trials Unit at Cardiff University on behalf of the NCRI Upper GI CSG.DiscussionFollowing encouraging results from previous trials, there is an interest in neo-adjuvant chemotherapy and CRT containing regimens for treatment of oesophageal adenocarcinoma. NEOSCOPE will first establish the efficacy, safety and feasibility of two different neo-adjuvant CRT regimens prior to a potential phase III trial.Trial registrationEudract No: 2012-000640-10. ClinicalTrials.gov: NCT01843829.

Perioperative chemotherapy versus neoadjuvant chemoradiotherapy for esophageal or GEJ adenocarcinoma: A propensity score‐matched analysis comparing toxicity, pathologic outcome, and survival

“…Therefore, subtle effects on progression‐free survival and overall survival cannot be excluded. Currently, several randomized trials comparing chemotherapy and nCRT regimens are underway and should resolve the limitations in the current literature (CROSS vs. MAGIC [NCT01726452], NEOSCOPE‐trial [NCT01843829], TOPGEAR‐trial [NCT01924819]).…”

Surgical treatment of esophageal cancer in the era of multimodality management

“…The Chinese CMISG1701 study compares overall survival between neoadjuvant chemotherapy (cisplatin/paclitaxel) with neoadjuvant chemoradiotherapy (cisplatin/paclitaxel with 40 Gy radiation), both followed by esophagectomy for locally advanced resectable esophageal squamous cell carcinoma . The NEOSCOPE study investigates whether induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin, both combined with 45 Gy radiation, is superior as preoperative regimen in pathological complete response of resectable esophageal adenocarcinoma . Finally, the PROTECT‐1402 study compares three cycles of FOLFOX combined with concurrent radiotherapy (41.4 Gy) or carboplatin and paclitaxel with the same radiation regimen for esophageal and junctional cancer .…”

Neoadjuvant treatment of locally advanced esophageal and junctional cancer: the evidence-base, current key questions and clinical trials

“…A recent interim report from the first 120 patients randomised showed no difference in toxicity between the two arms, with grade 3 or greater toxicity observed in approximately 20% in each arm with 85-90% of patients progressing to surgery (25) Other active Phase II trials are important on this theme. In NeoSCOPE (NCT01843829), the choice of an optimal chemotherapy regimen to pair with radiation therapy (45 Gy) is examined in a phase II trial of oxaliplatin/capecitabine (OXCAP-RT) versus carboplatin/paclitaxel (CarPac-RT) (26). It is a "pick a winner" design based on pCR,, with 38 patients with esophageal or junctional adenocarcinoma (AEG type I/II; ≥T3±≥N1) per treatment arm, the trial will be used to define the optimal regimen for a future phase III trial comparing neoadjuvant chemotherapy.…”