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

• Sponsor: Karolinska University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01362127
• Collaborator: University Hospital, Umeå (Other), Region Örebro County (Other), Sahlgrenska University Hospital, Sweden (Other), Ullevaal University Hospital (Other), Haukeland University Hospital (Other), Oslo University Hospital (Other), St. Olavs Hospital (Other), Malarhospital Eskilstuna (Other)
• Enrollment: 181
• Location: 1
• Arms: 2
• Actual Duration (Months): 140.8
• Patients Per Site Per Month: 1.3

Study Details

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
• 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: Oct 1, 2006
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 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 Names: 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 Names: 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 Names: 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. [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. [Five years follow up]

   Safety profile of carrying out radical surgery after respective neoadjuvant therapy.

2. HRQOL and Swallowing Function [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

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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
• First Posted: May 27, 2011
• Last Update Posted: Feb 26, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Magnus Nilsson, Ass Professor, Karolinska University Hospital: Histologically confirmed squamos cell carcinoma or adenocarcinoma of the esophagus and gastric cardia.Suitable for surgery.
• Additional relevant MeSH terms: Adenocarcinoma; Esophageal Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Carboplatin; Oxaliplatin

Study Results

Participant Flow

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 Participants	90	91	181
Age (Count of Participants)
<=18 years	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 (Count of Participants)
Female	18 20%	14 15.4%	32 17.7%
Male	72 80%	77 84.6%	149 82.3%
Region of Enrollment (participants) [Number]
Sweden	90 100%	91 100%	181 100%

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.
Measure Participants	78	78
Count of Participants [Participants]	22 24.4%	7 7.7%

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.
Measure Participants	90	91
Count of Participants [Participants]	79 87.8%	81 89%

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.
Measure Participants	80	74
Mean global QoL	67	69
Dysphagia score all	27	31

Adverse Events

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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Radiochemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/90 (63.3%)		41/91 (45.1%)
Blood and lymphatic system disorders
Neutropenia/thrombocytopenia	5/90 (5.6%)	5	2/91 (2.2%)	2
Cardiac disorders
Cardiovascular events	14/90 (15.6%)	14	7/91 (7.7%)	7
Death	2/90 (2.2%)	2	1/91 (1.1%)	1
Gastrointestinal disorders
Nausea and vomiting	6/90 (6.7%)	6	2/91 (2.2%)	2
Gastrointestinal symptoms	5/90 (5.6%)	5	1/91 (1.1%)	1
General disorders
Other	3/90 (3.3%)	3	3/91 (3.3%)	3
Infections and infestations
Infection	5/90 (5.6%)	5	5/91 (5.5%)	5
Investigations
SAE	57/90 (63.3%)	57	41/91 (45.1%)	41
Metabolism and nutrition disorders
Nutritional deficiency	13/90 (14.4%)	13	13/91 (14.3%)	13
Renal and urinary disorders
Renal failure	4/90 (4.4%)	4	7/91 (7.7%)	7
Other (Not Including Serious) Adverse Events
	Radiochemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/91 (0%)

Limitations/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.