Effect of Concurrent Capecitabine-based Long-term Radiotherapy Followed by XELOX Plus TME in Patients With High Risk Rectal Cancer: a Multi-centers, Randomized Controlled, Open-Label Trial

NCT03038256 | Unknown Phase 2 DMC

• 1 other identifier: 2016-12 EXPLORE
• Study Type: interventional
• Target: 244
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study was to evaluate the effect of concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX pre- a delayed TME compared with 6 cycles XELOX post- a Regular Timing TME in patients with high-risk rectal cancer defined by MRI.

Conditions

Rectal Cancer; Pathological Complete Response; Disease Free Survival

Keywords

High Risk Rectal Cancer; Total neoadjuvant chemoradiotherapy; Lengthening interval between radiotherapy and surgery

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  Pathological complete response (pCR) rate between control and intervention arm

  up to 30days after total mesorectal excision

Secondary Outcomes (4)

• Disease Free Survival

  3-year

• R0 of total mesorectal excision rate

  up to 30days after total mesorectal excision

• Surgery morbidity

  30 days and 12-months

• quality of surgery

  Time of surgery

Study Arms (2)

4 Cycles XELOX pre- TME

EXPERIMENTAL

experimental group (arm B): concurrent capecitabine-based long-term radiotherapy, 4 cycles of XELOX as neoadjuvant chemotherapy and TME surgery

Drug: concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX and a delayed TME

6 Cycles XELOX post- TME

ACTIVE COMPARATOR

control group (arm A): concurrent capecitabine-based long-term radiotherapy, TME surgery and 6 cycles of XELOX as adjuvant chemotherapy.

Drug: concurrent capecitabine-based long-term radiotherapy followed by a Regular TME and 6 Cycles XELOX

Interventions

concurrent capecitabine-based long-term radiotherapy followed by 4 cycles XELOX and a delayed TME DRUG

concurrent capecitabine-based long-term radiotherapy: capecitabine 825mg/m2,bid,d1-5, q week with Radiation treatment. Radiation treatment was given at 1·8 Gy per day, 5 days per week for 5-6 weeks, after a 45 Gy radiation dose in 25 fractions to the pelvis, a boost dose of 5·4 Gy in 3 fractions to the tumor bed or concurrent boosted. XELOX: Oxaliplatin: 130mg/m2,IV,d1; Capecitabine: 1000mg/m2,bid,d1-14; repeated every 3 weeks Surgery Procedure: Total Mesorectal Excision

4 Cycles XELOX pre- TME

concurrent capecitabine-based long-term radiotherapy followed by a Regular TME and 6 Cycles XELOX DRUG

concurrent capecitabine-based long-term radiotherapy: capecitabine 825mg/m2,bid,d1-5, q week with Radiation treatment. Radiation treatment was given at 1·8 Gy per day, 5 days per week for 5-6 weeks, after a 45 Gy radiation dose in 25 fractions to the pelvis, a boost dose of 5·4 Gy in 3 fractions to the tumor bed or concurrent boosted. XELOX: Oxaliplatin: 130mg/m2,IV,d1; Capecitabine: 1000mg/m2,bid,d1-14; repeated every 3 weeks Surgery Procedure: Total Mesorectal Excision

6 Cycles XELOX post- TME

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18-75 years;
• Histologically confirmed adenocarcinoma;
• The rectal adenocarcinoma 0-12cm from the anal margin on Magnetic resonance imaging (MRI) and/or rigid sigmoidoscopy;
• High risk of rectal cancer defined by high-resolution MRI: tumor invasion 5mm beyond the muscularis propria, or extramural vascular invasion, or circumferential resection margin unsafe, or the lower rectal cancer invades intersphincteric space, or rectal cancer invades the adjacent structures.
• Eastern Collaborative Oncology Group performance status score of 0 or 2
• Able and willing to give informed consent to participate.

You may not qualify if:

• Received preoperative chemoradiotherapy for rectal cancer before the recruitment of this study;
• Have metastatic disease (including non-regional lymph nodes metastases or resectable liver metastases);
• Other malignancies, non-adenocarcinoma rectal malignancies or rectal malignancies on the basis of inflammatory bowel disease;
• Emergency surgery due to bowel obstruction, perforation, bleeding, etc.;
• Abnormality of capecitabine absorption due to gastrointestinal disease e.g. short bowel syndrome, inflammation bowel disease, et al.;
• Unresectable concurrent intestinal lesions;
• Concurrent severe infection；
• Cardiac Disease：uncontrolled or symptomatic cardiac angina，or uncontrolled arrhythmias and hypertension, or severe congestive heart failure grade II or more based on New York Heart Association (NYHA); myocardial infarction within the past 12 months
• Peripheral neuropathy more than grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 3·0)
• Bone marrow, liver and kidney function are abnormal e.g., white blood cell ≤ 1.5 × 109 / L; platelet ≤ 100 × 109 / L; Haemoglobin ≤ 80 g/L; Bilirubin \> 1.5 times the upper limit; aspartate aminotransferase and alanine aminotransferase \> 2.5 times the upper limit; creatinine \> 1.5 times the upper limit;
• Pregnant or lactating women;
• Life prediction less than 3 months, other severe diseases;
• Contraindication to MRI; e.g. non-MRI compatible hip prosthesis, cardiac pacemaker;
• Contraindication to standard chemotherapy including drug interactions and glomerular filtration rate \<50 mL/min at baseline;
• Participators who had been recruited by other clinical trial within three months.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Peking University Cancer Hospital & Institute: collaborator
• Beijing Friendship Hospital: collaborator
• Peking Union Medical College Hospital: collaborator
• Chinese PLA General Hospital: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Fujian Medical University Union Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Xijing Hospital: collaborator
• Hebei Medical University Fourth Hospital: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Affiliated Hospital of Hebei University: collaborator

Study Sites (2)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

Beijing Friendship Hospital

Beijing, Beijing Municipality, China

NOT YET RECRUITING

Related Publications (10)

• Valentini V, van Stiphout RG, Lammering G, Gambacorta MA, Barba MC, Bebenek M, Bonnetain F, Bosset JF, Bujko K, Cionini L, Gerard JP, Rodel C, Sainato A, Sauer R, Minsky BD, Collette L, Lambin P. Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials. J Clin Oncol. 2011 Aug 10;29(23):3163-72. doi: 10.1200/JCO.2010.33.1595. Epub 2011 Jul 11.

  PMID: 21747092 RESULT

• Moran BJ. Predicting the risk and diminishing the consequences of anastomotic leakage after anterior resection for rectal cancer. Acta Chir Iugosl. 2010;57(3):47-50. doi: 10.2298/aci1003047m.

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• van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Epub 2011 May 17.

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• Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rodel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926-33. doi: 10.1200/JCO.2011.40.1836. Epub 2012 Apr 23.

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• Lutz MP, Zalcberg JR, Glynne-Jones R, Ruers T, Ducreux M, Arnold D, Aust D, Brown G, Bujko K, Cunningham C, Evrard S, Folprecht G, Gerard JP, Habr-Gama A, Haustermans K, Holm T, Kuhlmann KF, Lordick F, Mentha G, Moehler M, Nagtegaal ID, Pigazzi A, Pucciarelli S, Roth A, Rutten H, Schmoll HJ, Sorbye H, Van Cutsem E, Weitz J, Otto F. Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer. Eur J Cancer. 2016 Aug;63:11-24. doi: 10.1016/j.ejca.2016.04.010. Epub 2016 May 30.

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• Chua YJ, Barbachano Y, Cunningham D, Oates JR, Brown G, Wotherspoon A, Tait D, Massey A, Tebbutt NC, Chau I. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010 Mar;11(3):241-8. doi: 10.1016/S1470-2045(09)70381-X. Epub 2010 Jan 25.

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• Glynne-Jones R, Anyamene N, Moran B, Harrison M. Neoadjuvant chemotherapy in MRI-staged high-risk rectal cancer in addition to or as an alternative to preoperative chemoradiation? Ann Oncol. 2012 Oct;23(10):2517-2526. doi: 10.1093/annonc/mds010. Epub 2012 Feb 23.

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• Rodel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Strobel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. doi: 10.1016/S1470-2045(15)00159-X. Epub 2015 Jul 15.

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• Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. doi: 10.1200/JCO.2016.66.6198. Epub 2016 Aug 1.

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• Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. doi: 10.1016/S1470-2045(15)00004-2. Epub 2015 Jul 14.

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MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Yi Wang, MD, PHD

CONTACT

8610-88325813; wangyi@pkuph.edu.cn, jennifer_wy@me.com

Yingjiang Ye, MD, PHD

CONTACT

8610-88326608; yeyingjiang@pkuph.edu.cn, yjye101@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of GI Surgery

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: January 31, 2017
• Study Start: January 31, 2018
• Primary Completion: April 1, 2023
• Study Completion: June 1, 2025
• Last Updated: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (2)