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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Squamous Cell; Adenocarcinoma of the Esophagus and Gastric Cardia	Drug: Chemotherapy; Radiation: Radiochemotherapy	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 181 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Adjuvant Treatment of Cancer of the Esophagus or Cardia Before Resection With Curative Intent. Comparative Study Between Chemotherapy and Radiochemotherapy
• Actual Study Start Date: October 2006
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 25, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Radiochemotherapy; Arm I: Radiochemotherapy + Surgery	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.
Active Comparator: Chemotherapy; Arm II: Chemotherapy + surgery	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.

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Safety of Respective Neoadjuvant Therapies. [ Time Frame: Five years follow up ]
   Safety profile of carrying out radical surgery after respective neoadjuvant therapy.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Sweden

Upper Digestive Diseases. Department of surgery, Karolinska University Hospital

Stockholm, Sweden, 14186

Sponsors and Collaborators

Karolinska University Hospital

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

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Magnus Nilsson, Ass Professor, Karolinska University Hospital
• ClinicalTrials.gov Identifier: NCT01362127
• Other Study ID Numbers: EU-nr 2006-001785-16; 2006-001785-16 ( EudraCT Number )
• First Posted: May 27, 2011
• Results First Posted: February 26, 2020
• Last Update Posted: February 26, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Magnus Nilsson, Karolinska University Hospital:

Histologically confirmed squamos cell carcinoma or adenocarcinoma of the esophagus and gastric cardia.Suitable for surgery.

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Cisplatin; Carboplatin; Oxaliplatin; Antineoplastic Agents