Neoadjuvant Chemotherapy Versus Radiochemotherapy for Cancer of the Esophagus or Cardia (NeoRes)

• ClinicalTrials.gov Identifier: NCT01362127
• Recruitment Status: Completed
• First Posted: May 27, 2011
• Results First Posted: February 26, 2020
• Last Update Posted: February 26, 2020
• Sponsor: Karolinska University Hospital
• Collaborators: University Hospital, Umeå; Region Örebro County; Sahlgrenska University Hospital, Sweden; Ullevaal University Hospital; Haukeland University Hospital; Oslo University Hospital; St. Olavs Hospital; Malarhospital Eskilstuna
• Information provided by (Responsible Party): Magnus Nilsson, Karolinska University Hospital

Tracking Information

• First Submitted Date: May 26, 2011
• First Posted Date: May 27, 2011
• Results First Submitted Date: April 16, 2019
• Results First Posted Date: February 26, 2020
• Last Update Posted Date: February 26, 2020
• Actual Study Start Date: October 2006
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2020)

Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia. [ Time Frame: Therapy followed in 14-16 weeks before surgery. After surgery the patients will be followed until 60 weeks after completed therapy. ]

Chireac tumour regression grade

• Original Primary Outcome Measures (submitted: May 26, 2011): To evaluate whether radiochemotherapy gives higher complete histological response (pCR) after resection than chemotherapy alone in patients with resectable carcinoma of the esophagus and cardia. [ Time Frame: Therapy followed in 14-16 weeks before surgery. After surgery the patients will be followed until 60 weeks after completed therapy. ]

Current Secondary Outcome Measures (submitted: February 25, 2020)

• Safety of Respective Neoadjuvant Therapies. [ Time Frame: Five years follow up ]
  Safety profile of carrying out radical surgery after respective neoadjuvant therapy.
• HRQOL and Swallowing Function [ Time Frame: Entry study up to Five years follow up ]
  The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease specific questionnaires (QLQ-OES24/OG25). All items included in the questionnaires are analysed and also separate analysis of dysphagia questionnaires for oesophageal cancer were used, both clinically and psychometrically validated. All questions have four response alternatives (1, not at all; 2:a little, 3: quite a bit, 4: very much), except global scales which comprise seven response alternatives from poor to excellent. Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 according to the EORTC scoring manual. A higher score indicates either more symotoms or better function, depending on the question.

Original Secondary Outcome Measures (submitted: May 26, 2011)

To evaluate the safety of respective neoadjuvant therapies. [ Time Frame: Three years follow up ]

To assess the safety profile of carrying out radical surgery after respective neoadjuvant therapy. To study the overall and disease free survival in respective groups. To evaluate if pretreatment tumor characteristics predict the pCR and oncomplete pCR rates.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Neoadjuvant Chemotherapy Versus Radiochemotherapy for Cancer of the Esophagus or Cardia
• Official Title: Adjuvant Treatment of Cancer of the Esophagus or Cardia Before Resection With Curative Intent. Comparative Study Between Chemotherapy and Radiochemotherapy
• Brief Summary: The purpose of this randomized study is to clarify if neoadjuvant radiochemotherapy gives a higher degree of complete histological response than neoadjuvant chemotherapy before surgery in patients undergoing treatment for cancer of the esophagus or cardia.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Carcinoma, Squamous Cell
• Adenocarcinoma of the Esophagus and Gastric Cardia

Intervention

• Drug: Chemotherapy
  Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.
  Other Name: Suffering moderate/severe hearing impairment and/or tinnitus cisplatin can be replaced. If adenocarcinoma oxaliplatin.If squamos cell carcinoma carboplatin.
• Radiation: Radiochemotherapy
  Cisplantin 100 mg/m2 day 1. 5-fluoracil 750 mg/m2/24 hours infusion day 1-5. Three cycles. In the chemoradiation arm the radiotherapy start week 4 and continuing until week 7. Dose adjustet according to current LPK and TPK values.
  Other Name: Suffering moderate/severe hearing impairment and/or tinnitus cisplatin can be replaced. If adenocarcinoma oxaliplatin.If squamos cell carcinoma carboplatin.

Study Arms

• Active Comparator: Radiochemotherapy
  Arm I: Radiochemotherapy + Surgery
  Interventions:

  • Drug: Chemotherapy
  • Radiation: Radiochemotherapy
• Active Comparator: Chemotherapy
  Arm II: Chemotherapy + surgery
  Intervention: Drug: Chemotherapy

Publications *

• Klevebro F, Alexandersson von Dobeln G, Wang N, Johnsen G, Jacobsen AB, Friesland S, Hatlevoll I, Glenjen NI, Lind P, Tsai JA, Lundell L, Nilsson M. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016 Apr;27(4):660-7. doi: 10.1093/annonc/mdw010. Epub 2016 Jan 17.
• Sunde B, Klevebro F, Johar A, Johnsen G, Jacobsen AB, Glenjen NI, Friesland S, Lindblad M, Ajengui A, Lundell L, Lagergren P, Nilsson M. Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial). Br J Surg. 2019 Oct;106(11):1452-1463. doi: 10.1002/bjs.11246. Epub 2019 Aug 22.
• von Dobeln GA, Klevebro F, Jacobsen AB, Johannessen HO, Nielsen NH, Johnsen G, Hatlevoll I, Glenjen NI, Friesland S, Lundell L, Yu J, Nilsson M. Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial. Dis Esophagus. 2019 Feb 1;32(2). doi: 10.1093/dote/doy078.
• Klevebro F, Johnsen G, Johnson E, Viste A, Myrnas T, Szabo E, Jacobsen AB, Friesland S, Tsai JA, Persson S, Lindblad M, Lundell L, Nilsson M. Morbidity and mortality after surgery for cancer of the oesophagus and gastro-oesophageal junction: A randomized clinical trial of neoadjuvant chemotherapy vs. neoadjuvant chemoradiation. Eur J Surg Oncol. 2015 Jul;41(7):920-6. doi: 10.1016/j.ejso.2015.03.226. Epub 2015 Apr 8.
• Sunde B, Johnsen G, Jacobsen AB, Glenjen NI, Friesland S, Lindblad M, Rouvelas I, Wang N, Lundell L, Lagergren P, Nilsson M. Effects of neoadjuvant chemoradiotherapy vs chemotherapy alone on the relief of dysphagia in esophageal cancer patients: secondary endpoint analysis in a randomized trial. Dis Esophagus. 2019 Feb 1;32(2). doi: 10.1093/dote/doy069.
• Lund M, Tsai JA, Nilsson M, Winter R, Lundell L, Kalman S. Effects of neoadjuvant chemo or chemoradiotherapy for oesophageal cancer on perioperative haemodynamics: A prospective cohort study within a randomised clinical trial. Eur J Anaesthesiol. 2016 Sep;33(9):653-61. doi: 10.1097/EJA.0000000000000480.
• Lund M, Alexandersson von Dobeln G, Nilsson M, Winter R, Lundell L, Tsai JA, Kalman S. Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction - a prospective cohort pilot study within a randomized clinical trial. Radiat Oncol. 2015 Jan 13;10:16. doi: 10.1186/s13014-014-0310-7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 25, 2020): 181
• Original Estimated Enrollment (submitted: May 26, 2011): 180
• Actual Study Completion Date: June 25, 2018
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically verified squamos cell carcinoma, adenocarcinoma of the esopohagus or gastric cardia (type II)
• Tumor located in cervical oesophagus, not requiring laryngo-esophagectomy. Patients with performance status 0-1 axxording to WHO scale and with resectable tumours, as assessed at the prerandomisation evaluation
• Adequate haemotological function, defined as having WBC > 3 x 10(9)/litre and platelets > 100 x 10 (9)/litre.
• Adequate renal function defined as having normal serum creatinine level and/or calculated glomerular filtration rate > 60 ml/min.
• Tumour stage: T1Ni, T2N0, T2N1, T3N0, T3N1, M1a

Exclusion Criteria:

• Pregnancy and/or lactation. Women of childbearing ages can be included and provided that adequate contraceptive methods are used
• Patients with diabetes complications (e.g. rethinopathy, neuropathy) as well as patients with uncontrolled cardiac disease or myocard infarction within 12 months are considered unsuitable for chemoradiotherapy.
• Concomitant malignancy (< 5 years since diagnosis) that can interfere the interpretation of study results, ongoing antitumoral treatment.
• Patients being unable tom comply with the protocol
• Tumor stage T1 N0, T4 NX or TXNXM1b

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT01362127
• Other Study ID Numbers: EU-nr 2006-001785-16; 2006-001785-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Magnus Nilsson, Karolinska University Hospital
• Original Responsible Party: Professor Lars Lundell, Karolinska University Hospital
• Current Study Sponsor: Karolinska University Hospital
• Original Study Sponsor: Same as current

Collaborators

• University Hospital, Umeå
• Region Örebro County
• Sahlgrenska University Hospital, Sweden
• Ullevaal University Hospital
• Haukeland University Hospital
• Oslo University Hospital
• St. Olavs Hospital
• Malarhospital Eskilstuna

Investigators

• Principal Investigator: Magnus Nilsson, Professor; Karolinska University Hospital, Gastrocentrum
• Study Chair: Lars Lundell, Professor; Karolinska University Hospital, Gastrocentrum

• PRS Account: Karolinska University Hospital
• Verification Date: February 2020