MRI Simulation-guided Boost in Short-course Preoperative Radiotherapy for Unresectable Rectal Cancer

NCT ID: NCT03714490

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-23
• Study Completion Date: 2025-09-30

Brief Summary

Improvements in downstaging are required when using preoperative chemoradiation for unresectable rectal cancer. There is therefore a need to explore more effective schedules. The study arm will receive MRI simulation-guided boost in short-course preoperative radiotherapy followed by consolidation chemotherapy , which may enhance the shrinkage of tumor comparing with the concurrent chemoradiation.

Detailed Description

The study is a prospective phase II randomized multicenter trial. The purpose of this study is to compare short-term radiotherapy with MRI simulation-guided boost followed by consolidation chemotherapy(Experimental group) with preoperative long-term chemoradiotherapy(Control group) for middle-lower unresectable locally advanced rectal cancer evaluated by MRI. The primary endpoint is the rate of R0 resection and cCR, and the secondary objectives are local recurrence-free survival, distant metastasis-free survival, disease-free survival and overall survival at 3-year and 5-year follow up. Furthermore, pathological complete response rate, the acute and late toxicity profile and quality of life (QOL) after 3 years follow-up are secondary endpoints. The exploratory end point includes the circulating tumor DNA, and other potential biomarkers from tumor tissue and blood sample for treatment response and survival predicting. For each group, a plan for collection of serum/plasma/feces at baseline and different stages during or after treatment and for obtaining fresh tumor tissue for freezing prior to treatment was defined in the protocol.

The SUNRISE-trial has been designed by National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, and the hypothesis is R0 resection rate in Experimental group was superior to that in Control group.

Interim analysis design: As a phase II trial, the safety of experimental intervention is a major concern. We took the toxicity data from STELLAR, a phase III randomized study led by our center, as a reference. The incidence of G3 and above side effects in the short course radiotherapy with sequential neoadjuvant chemotherapy group was 28%, and that in the standard long-course concurrent chemoradiotherapy control group was 5%. Considering that boost dose may increase toxicity, if severe toxicity in the study group significantly exceeds that in the control group by more than 35%, it is up to the principal investigator to decide whether to modify the study protocol or terminate the study. The sample size of the interim analysis was calculated by the Z-pooled test, with α=0.05 (one-sided test), 1-β=0.90, using PASS 11 software. The frequency of the toxicity of G3 and above should be compared when neoadjuvant therapy was completed in 21 patients enrolled in each group.

Conditions

Rectal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental group

The intervention of Experimental group includes: Radiotherapy, followed by chemotherapy with capecitabine, oxaliplatin, and then surgery. The detail of procedure: 1, short-course preoperative radiotherapy(SCPRT) , which consists of SCPRT, 5 Gray(Gy) x 5, 4Gy for boost on the gross tumour volume(GTV) with MRI-simulation alone; 2,then after 7-10 days of radiotherapy completed, patients will receive consolidation 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.

Group Type: EXPERIMENTAL

SCPRT

Intervention Type: RADIATION

Short-course preoperative radiotherapy(SCPRT), which consists of 5 Gy x 5f and 4Gy for boost on the GTV with MRI-simulation alone.

CAPOX

Intervention Type: DRUG

Patients will receive consolidation chemotherapy after 7-10 days of SCPRT completed, 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 scheduled before surgery.

Control group

The intervention of Control group includes:Radiotherapy, capecitabine, and surgery. The detail of procedure: 1, long-term chemoradiotherapy(CRT), which consists of a long-term chemoradiation (2 Gy x 25 with capecitabine) preoperatively; 2, 6-8 weeks after chemoradiation, 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.

Group Type: ACTIVE_COMPARATOR

CRT

Intervention Type: RADIATION

Long-term chemoradiotherapy(CRT), which consists of a long-term chemoradiation (2 Gy x 25 with capecitabine) preoperatively.

Interventions

SCPRT

Short-course preoperative radiotherapy(SCPRT), which consists of 5 Gy x 5f and 4Gy for boost on the GTV with MRI-simulation alone.

Intervention Type: RADIATION

CRT

Long-term chemoradiotherapy(CRT), which consists of a long-term chemoradiation (2 Gy x 25 with capecitabine) preoperatively.

Intervention Type: RADIATION

CAPOX

Patients will receive consolidation chemotherapy after 7-10 days of SCPRT completed, 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 scheduled before surgery.

Intervention Type: DRUG

Other Intervention Names

capecitabine, oxaliplatin

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+)
• Mesorectal fascia(MRF)+ or T4b evaluated by 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

JIN JING

Professor, Director of medical services

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jing Jin, M.D.

Role: STUDY_DIRECTOR

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Locations

Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Jing Jin, M.D.

Role: CONTACT

jinjing@csco.org.cn

86-010-87788503

Wen-Yang Liu, M.D.

Role: CONTACT

liuwenyang26@163.com

13810753633

Facility Contacts

Jing Jin, MD

Role: primary

jingjin1025@163.com

+8613601365130

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Other Identifiers

NCC201807007

Identifier Type: -

Identifier Source: org_study_id