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Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer (NeoResII)

Primary Purpose

Cancer of the Esophagus

Status
Active
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Resective surgery
Sponsored by
Karolinska University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer of the Esophagus focused on measuring Adenocarcinoma, Squamous cell carcinoma, Gastroesophageal Junction

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically verified adenocarcinoma or SCC of the esophagus or GEJ Siewert type I and II.
  • Tumors should be resectable and without distant metastasis, as assessed after completed CRT.
  • Patients with performance status 0-1 according to the Eastern Cooperative Oncology Group (ECOG) scale at the pre CRT evaluation and judges to be fit for surgery at the pre and post CRT evaluations.
  • Pre CRT tumor stage: T1N1-3M0, T2N0-3M0, T3N0-3,M0, T4aN0-3,M0
  • Written informed consent
  • Completed at least 80% of the planned chemotherapy and at least 90% of the prescribed radiotherapy dose within the neoadjuvant CRT schedule according to protocol within a period of <36 days.

Exclusion Criteria:

  • Concomitant malignant diagnosis (excluding non-melanoma skin cancer) <5 years since current cancer diagnosis.
  • Ongoing antitumoral treatment irrespective of time since diagnosis of earlier malignancy.
  • Patients being unable to comply with the protocol for reasons of language or cognitive function.
  • Tumor stage T1N0, T4bNX or TXNXM1.
  • Carcinoma of the upper third of the esophagus (i.e. cervical and uppermost thoracic) for simplicity here defined as upper border of tumor above 22 cm from incisors at endoscopy.
  • Clear radiological signs of tumor progression during CRT on CT-scan after completion of CRT. PET is not used in this decision as FDG-activity often increase due to radiotherapy induced inflammation.

Sites / Locations

  • Department of Surgery Gastrocentrum Karolinska Univeristy Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Resective surgery after 4-6 weeks

Resective surgery after 10-12 weeks

Arm Description

Resective surgery 4-6 weeks after completed chemoradiotherapy (CRT)

Resective surgery 10-12 weeks after completed chemoradiotherapy (CRT)

Outcomes

Primary Outcome Measures

Complete histological response proportion, using the Chirieac grading system.

Secondary Outcome Measures

Overall primary tumor treatment response defined as complete histological response (Chirieac 0) and partial histological response (Chirieac 1 and 2) together.
ypN tumor status, classified as ypN0 to ypN3.
5 year survival by intention to treat and per protocol analyses in each study arm.
Proportion of disease free patients after 5 years by intention to treat and per protocol analyses in each study arm.
R0 resection rate in each study arm.
Resectability rate in each study arm.
Safety and toxicity (only grade 3-5 toxicity will be reported) ety and toxicity (only grade 3-5 toxicity will be reported)
According to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
Postoperative complications in each study arm.
Using the classification in the Swedish National Registry for Gastric and Esopgageal Cancer (NREV), including Clavien-Dindo classification.
Health-related quality of life (HRQOL).
Validated questionnaires that assess patients functions (physical, emotional, social, role and cognitive function), symptoms (e.g. fatique, pain, nausea/vomiting, appetite, dysphagia, eating difficulties and diarrhea) and global quality of life.
QUALYs at 5 year follow-up in each study arm.
Quality Adjusted Life Year assesses not only how much longer the treatment will allow the patient to live, but weighs in the quality of life with survival as a composite variable.
Correlation between symptom scores, endoscopy and radiology; and complete histological response.
Nutritional status of patients in each study arm.

Full Information

First Posted
February 22, 2015
Last Updated
September 4, 2019
Sponsor
Karolinska University Hospital
Collaborators
Oslo University Hospital, Haukeland University Hospital, St. Olavs Hospital, Lund University Hospital, Sahlgrenska University Hospital, Sweden, University Hospital, Linkoeping, Region Örebro County, University Hospital, Umeå
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1. Study Identification

Unique Protocol Identification Number
NCT02415101
Brief Title
Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer
Acronym
NeoResII
Official Title
Randomized Clinical Trial Comparing the Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Cancer of the Esophagus or Gastric Cardia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2015 (undefined)
Primary Completion Date
April 19, 2019 (Actual)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska University Hospital
Collaborators
Oslo University Hospital, Haukeland University Hospital, St. Olavs Hospital, Lund University Hospital, Sahlgrenska University Hospital, Sweden, University Hospital, Linkoeping, Region Örebro County, University Hospital, Umeå

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study compares outcomes with regard to the timing of resective surgery after neoadjuvant chemoradiotherapy (CRT) in cancer of the esophagus or gastric cardia. Patients are randomised to surgery either conventional 4-6 or 10-12 weeks after termination of CRT. The study hypothesis is that a longer delay improves histological response and decreases the risk of postoperative morbidity and mortality.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer of the Esophagus
Keywords
Adenocarcinoma, Squamous cell carcinoma, Gastroesophageal Junction

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
202 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Resective surgery after 4-6 weeks
Arm Type
Active Comparator
Arm Description
Resective surgery 4-6 weeks after completed chemoradiotherapy (CRT)
Arm Title
Resective surgery after 10-12 weeks
Arm Type
Active Comparator
Arm Description
Resective surgery 10-12 weeks after completed chemoradiotherapy (CRT)
Intervention Type
Procedure
Intervention Name(s)
Resective surgery
Primary Outcome Measure Information:
Title
Complete histological response proportion, using the Chirieac grading system.
Time Frame
analysis is completed 4 weeks after surgery
Secondary Outcome Measure Information:
Title
Overall primary tumor treatment response defined as complete histological response (Chirieac 0) and partial histological response (Chirieac 1 and 2) together.
Time Frame
analysis is completed 4 weeks after surgery
Title
ypN tumor status, classified as ypN0 to ypN3.
Time Frame
analysis is completed 4 weeks after surgery
Title
5 year survival by intention to treat and per protocol analyses in each study arm.
Time Frame
5 years
Title
Proportion of disease free patients after 5 years by intention to treat and per protocol analyses in each study arm.
Time Frame
5 years
Title
R0 resection rate in each study arm.
Time Frame
analysis is completed 4 weeks after surgery
Title
Resectability rate in each study arm.
Time Frame
4-6 or 10-12 weeks after completed CRT
Title
Safety and toxicity (only grade 3-5 toxicity will be reported) ety and toxicity (only grade 3-5 toxicity will be reported)
Description
According to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
Time Frame
4-6 or 10-12 weeks after completed CRT
Title
Postoperative complications in each study arm.
Description
Using the classification in the Swedish National Registry for Gastric and Esopgageal Cancer (NREV), including Clavien-Dindo classification.
Time Frame
30 days after surgery
Title
Health-related quality of life (HRQOL).
Description
Validated questionnaires that assess patients functions (physical, emotional, social, role and cognitive function), symptoms (e.g. fatique, pain, nausea/vomiting, appetite, dysphagia, eating difficulties and diarrhea) and global quality of life.
Time Frame
4-6 or 10-12 weeks prior to surgery (at randomization after completed CRT), within a week before surgery, 6 months postoperatively, 12 months postoperatively and then yearly until 5 years of follow-up.
Title
QUALYs at 5 year follow-up in each study arm.
Description
Quality Adjusted Life Year assesses not only how much longer the treatment will allow the patient to live, but weighs in the quality of life with survival as a composite variable.
Time Frame
5 years after surgery
Title
Correlation between symptom scores, endoscopy and radiology; and complete histological response.
Time Frame
4 weeks after surgery
Title
Nutritional status of patients in each study arm.
Time Frame
within a week before the start of CRT, within a week before surgery and 5 years after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically verified adenocarcinoma or SCC of the esophagus or GEJ Siewert type I and II. Tumors should be resectable and without distant metastasis, as assessed after completed CRT. Patients with performance status 0-1 according to the Eastern Cooperative Oncology Group (ECOG) scale at the pre CRT evaluation and judges to be fit for surgery at the pre and post CRT evaluations. Pre CRT tumor stage: T1N1-3M0, T2N0-3M0, T3N0-3,M0, T4aN0-3,M0 Written informed consent Completed at least 80% of the planned chemotherapy and at least 90% of the prescribed radiotherapy dose within the neoadjuvant CRT schedule according to protocol within a period of <36 days. Exclusion Criteria: Concomitant malignant diagnosis (excluding non-melanoma skin cancer) <5 years since current cancer diagnosis. Ongoing antitumoral treatment irrespective of time since diagnosis of earlier malignancy. Patients being unable to comply with the protocol for reasons of language or cognitive function. Tumor stage T1N0, T4bNX or TXNXM1. Carcinoma of the upper third of the esophagus (i.e. cervical and uppermost thoracic) for simplicity here defined as upper border of tumor above 22 cm from incisors at endoscopy. Clear radiological signs of tumor progression during CRT on CT-scan after completion of CRT. PET is not used in this decision as FDG-activity often increase due to radiotherapy induced inflammation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Magnus Nilsson, Prof
Organizational Affiliation
Karolinska University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Surgery Gastrocentrum Karolinska Univeristy Hospital
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
32833767
Citation
Nilsson K, Klevebro F, Rouvelas I, Lindblad M, Szabo E, Halldestam I, Smedh U, Wallner B, Johansson J, Johnsen G, Aahlin EK, Johannessen HO, Hjortland GO, Bartella I, Schroder W, Bruns C, Nilsson M. Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial: Standard Versus Prolonged Time to Surgery After Neoadjuvant Chemoradiotherapy for Esophageal Cancer. Ann Surg. 2020 Nov;272(5):684-689. doi: 10.1097/SLA.0000000000004340.
Results Reference
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Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer

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