Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly

NCT02992886 | Completed Phase 2 DMC

• 1 other identifier: CH-GI-098
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this multicenter phase II study is to evaluate the response rate, local control, disease-free survival and treatment-related toxicity of preoperative chemoradiation for intermediate or locally advanced rectal cancer in the fit elderly.

Conditions

Rectal Neoplasms Malignant

Keywords

elderly patients; rectal cancer; preoperative chemoradiotherapy; comprehensive geriatric assessment

Outcome Measures

Primary Outcomes (1)

• 2-year disease-free survival probability (%)

  The probability of staying free from recurrence at 2 year after surgery or clinical complete response of tumor validated on imaging or pathological examination.

  2 year

Secondary Outcomes (5)

• 5-year overall survival probability

  5 year

• 5-year cancer-specific survival probability

  5 year

• The ratio of patients occured pCR

  2 weeks after surgery

• The ratio of patients occured Grade 3 or higher adverse events.

  During chemoradiotherapy and within 180 days after surgery

• QOL

  Before and after chemoradiotherapy and surgery, and then follow up for 3 years

Other Outcomes (1)

• Exploratory endpoints

  5 years

Study Arms (1)

preCRT+surgery

EXPERIMENTAL

Treatment including preoperative chemoradiotherapy (preoperative radiation with concurrent chemotherapy) with Raltitrexed followed by surgery. Radiotherapy will be delivered to a planning target volume with a dose of 45-50.4Gy (1.8-2.0Gy daily) using with Intensity-Modulated Radiotherapy or Volumetric-Modulated Arc Therapy technique. During the radiation treatment, concurrent chemotherapy will be delivered (Raltitrexed, intravenous infusion, 3 mg/m2, on d1 and d22). Pelvic surgery is planned 6 weeks after completion of CRT based on the decision of MDT.

Radiation: Preoperative radiation; Drug: Raltitrexed; Procedure: Pelvic surgery

Interventions

Preoperative radiation RADIATION

Radiation treatment before surgery

Also known as: Preoperative radiotherapy

preCRT+surgery

Raltitrexed DRUG

concurrent chemotherapy

Also known as: Raltitrexed Injection

preCRT+surgery

Pelvic surgery PROCEDURE

preCRT+surgery

Eligibility Criteria

• Age: 71 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Rectal adenocarcinoma, clinical stage II/III(T3-4 or N+, AJCC 7th), and fulfils the intermediate or locally advanced risk category standard of ESMO recal cancer clinical practice guidelines 2013.
• KPS status no less than 70; Charlson comorbidity no more than 2; Fit status evaluated by CGA.
• Life expectancy more than 6 months.
• Hemoglobin \>= 100g/L, white blood cell \>= 3.5\*10E9/L, neutrophil \>= 1.5\*10E9/L, platelet \>= 100\*10E9/L.
• Creatin normal, Total bilirubin normal, AST and AST normal, AKP normal.
• Do not receive surgery ( except palliative colostomy) or chemotherapy or other anti-cancer treatment.
• No previously pelvic irradiation history.
• Through MDT discussion, the patient is considered to be candidate for preoperative CRT followed by surgery.
• Informed consent signed.

You may not qualify if:

• Other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma.
• Allergy history to analog of quinazoline folate.
• Active infection existed.
• Severe complication, such as acute myocardial infarction in 6 months, uncontrolled diabetes ( Plasma glucose concentrations in any time of a day≥11.1mmol/L）, severe cardiac arrhythmia, etc.
• Anticipate other clinical trials in four weeks before enrollment.

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead

Study Sites (1)

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

Beijing, Beijing Municipality, 100021, China

Location

Related Publications (16)

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  PMID: 16094710 BACKGROUND

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  PMID: 20334979 BACKGROUND

• Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829.

  PMID: 16971718 BACKGROUND

• Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. doi: 10.1200/JCO.2006.06.7629.

  PMID: 17008704 BACKGROUND

• Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484-0.

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• Teoh S, Muirhead R. Rectal Radiotherapy--Intensity-modulated Radiotherapy Delivery, Delineation and Doses. Clin Oncol (R Coll Radiol). 2016 Feb;28(2):93-102. doi: 10.1016/j.clon.2015.10.012. Epub 2015 Nov 28.

  PMID: 26643092 BACKGROUND

• Tang Y, Liu WY, Jin J, Zhang HZ, Yang L, Ren H, Fang H, Wang WH, Song YW, Liu YP, Wang SL, Li YX. Preoperative chemoradiation with capecitabine for rectal cancer in elderly patients: a phase I trial. Int J Colorectal Dis. 2016 Aug;31(8):1547-9. doi: 10.1007/s00384-016-2577-7. Epub 2016 Apr 8. No abstract available.

  PMID: 27059037 BACKGROUND

• Thomas RJ, Williams M, Garcia-Vargas J. Lessons learned from raltitrexed--quality assurance, patient education and intensive supportive drugs to optimise tolerability. Clin Oncol (R Coll Radiol). 2003 Aug;15(5):227-32. doi: 10.1016/s0936-6555(03)00092-x.

  PMID: 12924450 BACKGROUND

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• Feliu J, Mel JR, Camps C, Escudero P, Aparicio J, Menendez D, Garcia Giron C, Rodriguez MR, Sanchez JJ, Gonzalez Baron M; Oncopaz Cooperative Group Associated Hospitals. Raltitrexed in the treatment of elderly patients with advanced colorectal cancer: an active and low toxicity regimen. Eur J Cancer. 2002 Jun;38(9):1204-11. doi: 10.1016/s0959-8049(02)00005-9.

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• Valentini V, Doglietto GB, Morganti AG, Turriziani A, Smaniotto D, De Santis M, Ratto C, Sofo L, Cellini N. Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study. Eur J Cancer. 2001 Nov;37(16):2050-5. doi: 10.1016/s0959-8049(01)00247-7.

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• Francois E, Azria D, Gourgou-Bourgade S, Jarlier M, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Seitz JF, Conroy T, Juzyna B, Gerard JP. Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: tolerance and efficacy. Radiother Oncol. 2014 Jan;110(1):144-9. doi: 10.1016/j.radonc.2013.10.019. Epub 2014 Jan 10.

  PMID: 24418359 BACKGROUND

• Glimelius B, Tiret E, Cervantes A, Arnold D; ESMO Guidelines Working Group. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi81-8. doi: 10.1093/annonc/mdt240. No abstract available.

  PMID: 24078665 BACKGROUND

• Liu WY, Tang Y, Li N, Tang Y, Cheng YJ, Yang L, Fang H, Lu NN, Qi SN, Chen B, Wang SL, Song YW, Liu YP, Li YX, Liu Z, Liang JW, Pei W, Wang XS, Zhang HZ, Wang J, Zhou HT, Jin J. Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial. BMC Geriatr. 2024 May 21;24(1):442. doi: 10.1186/s12877-024-05046-6.

  PMID: 38773457 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

raltitrexed

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

Study Officials

• Jing Jin, MD

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair of Radiation Oncology

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 14, 2016
• Study Start: September 1, 2016
• Primary Completion: May 1, 2021
• Study Completion: August 1, 2021
• Last Updated: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)