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 Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Carcinoma, Squamous Cell; Adenocarcinoma of the Esophagus and Gastric Cardia
• Interventions: Drug: Chemotherapy; Radiation: Radiochemotherapy
• Enrollment: 181

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Radiochemotherapy	Chemotherapy
Arm/Group Description	Radiochemotherapy + Surgery 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.	Chemotherapy + surgery 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. 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.
Period Title: Overall Study
Started	90	91
Completed	90	91
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Radiochemotherapy	Chemotherapy	Total
Arm/Group Description		Radiochemotherapy + Surgery 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.	Chemotherapy + surgery 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. 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.	Total of all reporting groups
Overall Number of Baseline Participants		90	91	181
Baseline Analysis Population Description		see Klevebro et al Annals of Oncology, primary outcome
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	90 participants	91 participants	181 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	52 57.8%	55 60.4%	107 59.1%
	>=65 years	38 42.2%	36 39.6%	74 40.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	90 participants	91 participants	181 participants
	Female	18 20.0%	14 15.4%	32 17.7%
	Male	72 80.0%	77 84.6%	149 82.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Sweden	Number Analyzed	90 participants	91 participants	181 participants
		90	91	181

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiochemotherapy	Chemotherapy
Arm/Group Description:	Radiochemotherapy + Surgery 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.	Chemotherapy + surgery 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. 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.
Overall Number of Participants Analyzed	78	78
Measure Type: Count of Participants; Unit of Measure: Participants
	22 28.2%	7 9.0%

2. Secondary Outcome

Title	Safety of Respective Neoadjuvant Therapies.
Description	Safety profile of carrying out radical surgery after respective neoadjuvant therapy.
Time Frame	Five years follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiochemotherapy	Chemotherapy
Arm/Group Description:	Radiochemotherapy + Surgery 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.	Chemotherapy + surgery 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. 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.
Overall Number of Participants Analyzed	90	91
Measure Type: Count of Participants; Unit of Measure: Participants
	79 87.8%	81 89.0%

3. Secondary Outcome

Title	HRQOL and Swallowing Function
Description	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.
Time Frame	Entry study up to Five years follow up

Outcome Measure Data

Analysis Population Description

Number of patients who responded to quality of Life instruments the EORTC QLQ-C30 and the oesophageal specific instrument

Arm/Group Title	Radiochemotherapy	Chemotherapy
Arm/Group Description:	Radiochemotherapy + Surgery 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.	Chemotherapy + surgery 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. 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.
Overall Number of Participants Analyzed	80	74
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Mean global QoL	67; (62 to 72)	69; (63 to 74)
Dysphagia score all	27; (20 to 34)	31; (24 to 39)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Radiochemotherapy		Chemotherapy
Arm/Group Description	Radiochemotherapy + Surgery 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.		Chemotherapy + surgery 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. 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.
All-Cause Mortality
	Radiochemotherapy		Chemotherapy
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Radiochemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/90 (63.33%)		41/91 (45.05%)
Blood and lymphatic system disorders
Neutropenia/thrombocytopenia †	5/90 (5.56%)	5	2/91 (2.20%)	2
Cardiac disorders
Cardiovascular events †	14/90 (15.56%)	14	7/91 (7.69%)	7
Death †	2/90 (2.22%)	2	1/91 (1.10%)	1
Gastrointestinal disorders
Nausea and vomiting †	6/90 (6.67%)	6	2/91 (2.20%)	2
Gastrointestinal symptoms †	5/90 (5.56%)	5	1/91 (1.10%)	1
General disorders
Other †	3/90 (3.33%)	3	3/91 (3.30%)	3
Infections and infestations
Infection †	5/90 (5.56%)	5	5/91 (5.49%)	5
Investigations
SAE †	57/90 (63.33%)	57	41/91 (45.05%)	41
Metabolism and nutrition disorders
Nutritional deficiency †	13/90 (14.44%)	13	13/91 (14.29%)	13
Renal and urinary disorders
Renal failure †	4/90 (4.44%)	4	7/91 (7.69%)	7
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Radiochemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0.00%)		0/91 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Fredrik Klevebro
• Organization: Karolinska Institutet
• Phone: +46858580000 ext 11111
• EMail: fredrik.klevebro@ki.se

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, Karolinska University Hospital
• ClinicalTrials.gov Identifier: NCT01362127
• Other Study ID Numbers: EU-nr 2006-001785-16; 2006-001785-16 ( EudraCT Number )
• First Submitted: May 26, 2011
• First Posted: May 27, 2011
• Results First Submitted: April 16, 2019
• Results First Posted: February 26, 2020
• Last Update Posted: February 26, 2020