Clinical trial NCT01362127: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Squamous Cell
Adenocarcinoma of the Esophagus and Gastric Cardia
Keywords: Histologically confirmed squamos cell carcinoma or adenocarcinoma of the esophagus and gastric cardia.Suitable for surgery.
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: University Hospital, Umeå
name: Region Örebro County
name: Sahlgrenska University Hospital
name: Ullevaal University Hospital
name: Haukeland University Hospital
name: Oslo University Hospital
name: St. Olavs Hospital
name: Malarhospital Eskilstuna
First posted: 2011-05-27
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia.
timeFrame: Therapy followed in 14-16 weeks before surgery. After surgery the patients will be followed until 60 weeks after completed therapy.
Secondary outcomes:
measure: Safety of Respective Neoadjuvant Therapies.
timeFrame: Five years follow up
measure: HRQOL and Swallowing Function
timeFrame: Entry study up to Five years follow up
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Upper Digestive Diseases. Department of surgery, Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital, Gastrocentrum
name: Magnus Nilsson, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska University Hospital, Gastrocentrum
name: Lars Lundell, Professor
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.