search
Back to results

Optimization of Preoperative Treatment in Locally Advanced Rectal Cancer (STELLAR)

Primary Purpose

Cancer, Rectum

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Short-course radiotherapy with neoadjuvant chemotherapy
Long-term chemoradiotherapy
Sponsored by
Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer, Rectum focused on measuring rectal cancer, short-term radiotherapy, neoadjuvant chemotherapy, total mesorectal excision

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

TNT group

CRT group

Arm Description

The intervention of TNT group is Short-course radiotherapy with neoadjuvant chemotherapy, which consists of a short-course radiotherapy (SCRT, 5 Gy x 5 alone), then after 7-10 days of radiotherapy completed, patients will receive neoadjuvant chemotherapy, given in 3 week cycle of capecitabine 1000 mg/m2 twice daily, day 1-14 combined with oxaliplatin 130 mg/m2 once. In total, 4 cycles of neoadjuvant chemotherapy are prescribed preoperatively, then followed by a total mesorectal excision(TME) and postoperative adjuvant chemotherapy. If patients are eligible for postoperative chemotherapy this should consist of at least 2 cycles, which are the same as neoadjuvant chemotherapy.

The intervention of CRT group is long-term chemoradiotherapy(CRT), which consists of a long-term chemoradiation (2 Gy x 25 with capecitabine) preoperatively, followed by a total mesorectal excision(TME) and then postoperative adjuvant chemotherapy. The radiotherapy is given in combination with capecitabine in a dose of 825 mg/m2 twice daily on days when radiotherapy, excluding weekends. If patients are eligible for postoperative chemotherapy this should consist of at least 6 cycles of capecitabine 1000 mg/m2 twice daily, day 1-14 combined with oxaliplatin 130 mg/m2 once every 3 weeks.

Outcomes

Primary Outcome Measures

Disease-free survival rate

Secondary Outcome Measures

Overall survival rate
Distance metastasis free survival rate
Locoregional recurrence free survival rate
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.
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.
Radical resection (R0)
R0 resection rate is R0 resection probability of radical surgery in patients with locally advanced rectal cancer after neoadjuvant therapy
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
Quality of life (QoL)
Quality of life will be assessed using the EORTC QLQ C30, EORTC QLQ Cr29 and Wexner score.

Full Information

First Posted
August 21, 2015
Last Updated
July 10, 2021
Sponsor
Chinese Academy of Medical Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT02533271
Brief Title
Optimization of Preoperative Treatment in Locally Advanced Rectal Cancer
Acronym
STELLAR
Official Title
Phase III Study of Short-term Radiotherapy Plus Neoadjuvant Chemotherapy Versus Preoperative Long-term Chemoradiotherapy in Locally Advanced Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 2015 (undefined)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Rectum
Keywords
rectal cancer, short-term radiotherapy, neoadjuvant chemotherapy, total mesorectal excision

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
600 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TNT group
Arm Type
Experimental
Arm Description
The intervention of TNT group is Short-course radiotherapy with neoadjuvant chemotherapy, which consists of a short-course radiotherapy (SCRT, 5 Gy x 5 alone), then after 7-10 days of radiotherapy completed, patients will receive neoadjuvant chemotherapy, given in 3 week cycle of capecitabine 1000 mg/m2 twice daily, day 1-14 combined with oxaliplatin 130 mg/m2 once. In total, 4 cycles of neoadjuvant chemotherapy are prescribed preoperatively, then followed by a total mesorectal excision(TME) and postoperative adjuvant chemotherapy. If patients are eligible for postoperative chemotherapy this should consist of at least 2 cycles, which are the same as neoadjuvant chemotherapy.
Arm Title
CRT group
Arm Type
Other
Arm Description
The intervention of CRT group is long-term chemoradiotherapy(CRT), which consists of a long-term chemoradiation (2 Gy x 25 with capecitabine) preoperatively, followed by a total mesorectal excision(TME) and then postoperative adjuvant chemotherapy. The radiotherapy is given in combination with capecitabine in a dose of 825 mg/m2 twice daily on days when radiotherapy, excluding weekends. If patients are eligible for postoperative chemotherapy this should consist of at least 6 cycles of capecitabine 1000 mg/m2 twice daily, day 1-14 combined with oxaliplatin 130 mg/m2 once every 3 weeks.
Intervention Type
Radiation
Intervention Name(s)
Short-course radiotherapy with neoadjuvant chemotherapy
Intervention Description
Short-course radiotherapy with 4 cycles of neoadjuvant chemotherapy
Intervention Type
Radiation
Intervention Name(s)
Long-term chemoradiotherapy
Intervention Description
Standard chemoradiotherapy
Primary Outcome Measure Information:
Title
Disease-free survival rate
Time Frame
three year
Secondary Outcome Measure Information:
Title
Overall survival rate
Time Frame
three year
Title
Distance metastasis free survival rate
Time Frame
three year
Title
Locoregional recurrence free survival rate
Time Frame
three year
Title
Incidence of surgical complications
Description
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.
Time Frame
one month
Title
Incidence of acute toxicities during radiation or chemotherapy
Description
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.
Time Frame
three months
Title
Radical resection (R0)
Description
R0 resection rate is R0 resection probability of radical surgery in patients with locally advanced rectal cancer after neoadjuvant therapy
Time Frame
one year
Title
The rate of pathological complete response (pCR)
Description
PCR rate is pathological ypT0N0 probability of radical surgery in patients with locally advanced rectal cancer after neoadjuvant therapy
Time Frame
one year
Title
Quality of life (QoL)
Description
Quality of life will be assessed using the EORTC QLQ C30, EORTC QLQ Cr29 and Wexner score.
Time Frame
up to three years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuan Tang
Phone
+86-15011304945
Email
tangyuan82@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jing Jin
Phone
+86-13601365130
Email
jingjin1025@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jing Jin
Organizational Affiliation
Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Tang
Phone
+86-15011304945
Email
tangyuan82@126.com
First Name & Middle Initial & Last Name & Degree
Jing Jin
Phone
+86-13601365130
Email
jingjin1025@163.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35263150
Citation
Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX. Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR). J Clin Oncol. 2022 May 20;40(15):1681-1692. doi: 10.1200/JCO.21.01667. Epub 2022 Mar 9.
Results Reference
derived

Learn more about this trial

Optimization of Preoperative Treatment in Locally Advanced Rectal Cancer

We'll reach out to this number within 24 hrs