Clinical trial NCT02415101: Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer
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
Overall status: UNKNOWN
Phase: NA
Conditions: Cancer of the Esophagus
Keywords: Adenocarcinoma
Squamous cell carcinoma
Gastroesophageal Junction
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
name: Haukeland University Hospital
name: St. Olavs Hospital
name: Lund University Hospital
name: Sahlgrenska University Hospital
name: University Hospital, Linkoeping
name: Region Örebro County
name: University Hospital, Umeå
First posted: 2015-04-14
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Complete histological response proportion, using the Chirieac grading system.
timeFrame: analysis is completed 4 weeks after surgery
Secondary outcomes:
measure: Overall primary tumor treatment response defined as complete histological response (Chirieac 0) and partial histological response (Chirieac 1 and 2) together.
timeFrame: analysis is completed 4 weeks after surgery
measure: ypN tumor status, classified as ypN0 to ypN3.
timeFrame: analysis is completed 4 weeks after surgery
measure: 5 year survival by intention to treat and per protocol analyses in each study arm.
timeFrame: 5 years
measure: Proportion of disease free patients after 5 years by intention to treat and per protocol analyses in each study arm.
timeFrame: 5 years
measure: R0 resection rate in each study arm.
timeFrame: analysis is completed 4 weeks after surgery
measure: Resectability rate in each study arm.
timeFrame: 4-6 or 10-12 weeks after completed CRT
measure: Safety and toxicity (only grade 3-5 toxicity will be reported) ety and toxicity (only grade 3-5 toxicity will be reported)
timeFrame: 4-6 or 10-12 weeks after completed CRT
measure: Postoperative complications in each study arm.
timeFrame: 30 days after surgery
measure: Health-related quality of life (HRQOL).
timeFrame: 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.
measure: QUALYs at 5 year follow-up in each study arm.
timeFrame: 5 years after surgery
measure: Correlation between symptom scores, endoscopy and radiology; and complete histological response.
timeFrame: 4 weeks after surgery
measure: Nutritional status of patients in each study arm.
timeFrame: within a week before the start of CRT, within a week before surgery and 5 years after surgery
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Department of Surgery Gastrocentrum Karolinska Univeristy Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Magnus Nilsson, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.