Optimization of Preoperative Treatment in Locally Advanced Rectal Cancer

Cancer, Rectum Clinical Trial

— STELLAR  

Official title:

Phase III Study of Short-term Radiotherapy Plus Neoadjuvant Chemotherapy Versus Preoperative Long-term Chemoradiotherapy in Locally Advanced Rectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02533271
• Other study ID #: XT2015-03
• Secondary ID: CH-GI-090
• Status: Recruiting
• Phase: Phase 3
• Start date: August 2015
• Est. completion date: August 2025

Study information

• Verified date: July 2021
• Source: Chinese Academy of Medical Sciences
• Contact: Yuan Tang
• Phone: +86-15011304945
• Email: tangyuan82[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare effectiveness of short-term radiotherapy with neoadjuvant chemotherapy(TNT group) with preoperative long-term chemoradiotherapy(CRT group) in locally advanced rectal cancer. The hypothesis is 3-year disease-free survival in TNT group was non-inferior to that in CRT group.

Description:

The study is a prospective phase III randomized multicenter trial. The purpose of this study is to compare short-term radiotherapy with neoadjuvant chemotherapy(TNT group) with preoperative long-term chemoradiotherapy(CRT group) for middle-lower locally advanced rectal cancer. The primary endpoint is 3-year disease-free survival,defined as the interval from randomization to the first occurrence of local-regional failure, distant metastasis, second primary tumor or death from any cause. The primary hypothesis was that DFS in the TNT group would be non-inferior to that in the CRT group. After preoperative radiotherapy and surgery, the DFS rate of LARC fluctuated from 50% to 65%. Assuming a 3-year DFS rate in CRT group is 65%, we consider the 3-year DFS rate in the TNT group is not lower than 54% (e.g., a margin of 11% or equivalently, hazard ratio (HR) < 1.43). Guarding against a 5% ineligibility or drop-out rate, the accrual target was 600 patients, with the final analysis to occur after at least 194 DFS events to provide at least 80% power at 1-sided type 1 error of 0.05. The choices of type 1 error and power were made to provide an appropriate comprise between feasibility, timeliness and statistical rigor of evidence generation.

This study seeks to compare outcomes between two groups with respect to rates of overall survival(OS), distance metastasis free survival (DMFS), and locoregional recurrence free survival (LRRFS).In addition, acute and late toxicity profile, completion of preoperative treatment, the proportion of patients with radical resection (R0), surgical complication profile, the rate of pathological complete response (pCR), and quality of life (QoL) are also secondary endpoints.

The STELLAR-trial has been designed by National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, and the hypothesis is 3-year disease-free survival in TNT group was non-inferior to that in CRT group.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: August 2025
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Biopsy proven rectal adenocarcinoma;

• Distance between tumour and anal verge= 10cm;

• Locally advanced tumour;(AJCC Cancer Staging:T3, T4 or N+)

• Cancer Staging must be based on pelvic MRI;

• Eastern Cooperative Oncology Group(ECOG) performance score = 1;

• Written informed consent;

• Mentally and physically fit for chemotherapy;

• Adequate blood counts: White blood cell count =3.5 x 109/L Haemoglobin levels =100g/L Platelet count =100 x 109/L Creatinine levels =1.0× upper normal limit(UNL) Urea nitrogen levels =1.0× upper normal limit(UNL) Alanine aminotransferase(ALT) =1.5× upper normal limit(UNL) Aspartate aminotransferase(AST) =1.5× upper normal limit(UNL) Alkaline phosphatase(ALP) =1.5× upper normal limit(UNL) Total bilirubin(TBIL) =1.5× upper normal limit(UNL)

• No excision of tumor, chemotherapy or other anti-tumor treatment after the diagnosis.

Exclusion Criteria:

• Distant metastases;

• Recurrent rectal cancer;

• Active Crohn's disease or ulcerative colitis;

• Concomitant malignancies;(except basocellular carcinoma or in-situ cervical carcinoma)

• Allergic to Fluorouracil or Platinum drugs;

• Contraindications to MRI for any reason;

• Concurrent uncontrolled medical condition;

• Pregnancy or breast feeding;

• Known malabsorption syndromes or lack of physical integrity of upper gastrointestinal tract;

• Symptoms or history of peripheral neuropathy

Related Conditions & MeSH terms

• Cancer, Rectum
• Rectal Neoplasms

Intervention

Radiation:
• Short-course radiotherapy with neoadjuvant chemotherapy
Short-course radiotherapy with 4 cycles of neoadjuvant chemotherapy
• Long-term chemoradiotherapy
Standard chemoradiotherapy

Locations

Country	Name	City	State
China	Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival rate		three year
Secondary	Overall survival rate		three year
Secondary	Distance metastasis free survival rate		three year
Secondary	Locoregional recurrence free survival rate		three year
Secondary	Incidence of surgical complications	Surgical complications are defined as those occurring within 30 days after surgery, such as re-operation, anastomotic fistula, bleeding, infection and death related to the operation, etc.	one month
Secondary	Incidence of acute toxicities during radiation or chemotherapy	Number of participants with abnormal laboratory values and/or adverse events that are related to radiation or chemotherapy as assessed by Common Toxicity Criteria for Adverse Effects(CTCAE) v4.0.	three months
Secondary	Radical resection (R0)	R0 resection rate is R0 resection probability of radical surgery in patients with locally advanced rectal cancer after neoadjuvant therapy	one year
Secondary	The rate of pathological complete response (pCR)	PCR rate is pathological ypT0N0 probability of radical surgery in patients with locally advanced rectal cancer after neoadjuvant therapy	one year
Secondary	Quality of life (QoL)	Quality of life will be assessed using the EORTC QLQ C30, EORTC QLQ Cr29 and Wexner score.	up to three years