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Rectal Neoplasms MalignantPhase 2NCT02992886

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

A Phase 2 study testing Preoperative radiation, Raltitrexed and Pelvic surgery in people with Rectal Neoplasms Malignant, run by Chinese Academy of Medical Sciences at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 71 years and older
Conditions the study is for
Rectal Neoplasms Malignant
What is being tested?
Preoperative radiation, Raltitrexed and Pelvic surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
1 siteChina
Study dates
Sep 2016to Aug 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 71 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • No previously pelvic irradiation history.
  • Through MDT discussion, the patient is considered to be candidate for preoperative CRT followed by surgery.
  • Informed consent signed.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

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

    Beijing, Beijing Municipality, 100021

Other trials in China

About this study

Official title: Multicenter, Phase II Study of Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly

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.

Read the detailed description

The concurrent chemoradiotherapy has become the standard treatment for patients with intermediate or locally advanced rectal cancer. However, the data from prospective trial for elderly patients is still lacking.

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 with Raltitrexed for intermediate or locally advanced rectal cancer in the fit elderly aged 70 years above.

And all the participants have to be evaluated by comprehensive geriatric assessment (CGA). Clinical stage was evaluated by chest and abdominal computed tomography, endorectal ultrasound, and/or pelvic magnetic resonance imaging.

5 weeks after the preCRT, the multi-disciplinary team decided the following treatment of patients based on imaging evaluation. Surgical resection would be done with a minimum interval of 6 weeks after the last radiation. Acute toxicity was evaluated during and within 2 weeks after CRT. Toxicities were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

Sample size consideration.It has been calculated that 68 patients will need to be included, according to the following assumptions:

Recruitment period of 24 months. Minimum follow-up period of 24 months. We estimated that 51 patients were required to test the hypothesis that the 2-year DFS was equal to or greater than 78% with 80% power and to reject the hypothesis that the 2-year DFS rate was less than 63% at a significance level of 5% (one sided).Taking into account that a 5% percentage of losses, 20% of patients will refuse surgery, 68 patients are expected to be included in the study.

The interim analysis design. An interim safety evaluation will be carried out when 39 patients have finished their preoperative CRT. As the tolerance of elderly patients for nonhematological toxicities (such as diarrhoea) was often more poor than hematological toxicities, we estimated that 39 patients were required to test the hypothesis that the nonhematological G3 or higher acute toxicities rate was equal to or less than 21% ( safety result of patients aged 70 years or older from ACCOR12/PRODIGE 2 phase III trial) with 80% power and to reject the hypothesis that the rate was more than 36% at a significance level of 10% (one sided). If nonhematological G3 or higher acute toxicites is observed in12 or more patients, the H0 hypothesis will be rejected, and the protocal should be re-evaluated.

Biospecimen Retention. Blood, plasma, feces and tissue (optional). Feces were collected before any treatment. Peripheral blood samples of 10-20mL were collected from the patients for CTCs analysis, exploration analysis for frailty and tumor marker before and after preCRT, before and after surgery, and then on each follow up visit, according to our study protocal.

Being tested
Preoperative radiation, Raltitrexed, Pelvic surgery
Keywords
elderly patients, rectal cancer, preoperative chemoradiotherapy, comprehensive geriatric assessment
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Preoperative radiationRadiation

    Also called Preoperative radiotherapy

    Radiation treatment before surgery

  • RaltitrexedDrug

    Also called Raltitrexed Injection

    concurrent chemotherapy

  • Pelvic surgeryProcedure or surgery

Study groups in NCT02992886
Study groupRoleWhat they receive
preCRT+surgeryExperimentalTreatment 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.
Receives: Radiation: Preoperative radiation; Drug: Raltitrexed; Procedure: Pelvic surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 year

Secondary outcomes (5)

  1. 5-year overall survival probability

    The probability of staying alive at 5 year after surgery or end of CRT (for those who did not receive surgery).

    Measured: 5 year

  2. 5-year cancer-specific survival probability

    The probability of staying free from death caused by cancer at 5 year after surgery or end of CRT (for those who did not receive surgery).

    Measured: 5 year

  3. The ratio of patients occured pCR

    The ratio of patients occured pathological complete response of tumor.

    Measured: 2 weeks after surgery

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

    Measured: During chemoradiotherapy and within 180 days after surgery

  5. QOL

    The quality of life assessment score by EORTC QLQ-C30 and EORTC QLQ-CR29.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionMay 2021
  4. Study completionAug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02992886
Sponsor's protocol ID
CH-GI-098
Status last verified
Sep 2021
First submitted
30 Nov 2016
Last updated
9 Sep 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, Kohne CH, Rostoft S, Lemmens V, Mitry E, Rutten H, Sargent D, Sastre J, Seymour M, Starling N, Van Cutsem E, Aapro M. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2015 Mar;26(3):463-76. doi: 10.1093/annonc/mdu253. Epub 2014 Jul 11.

    PubMed 25015334

  • Li M, Gu J. Changing patterns of colorectal cancer in China over a period of 20 years. World J Gastroenterol. 2005 Aug 14;11(30):4685-8. doi: 10.3748/wjg.v11.i30.4685.

    PubMed 16094710

  • Fiorica F, Cartei F, Licata A, Enea M, Ursino S, Colosimo C, Camma C. Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data. Cancer Treat Rev. 2010 Nov;36(7):539-49. doi: 10.1016/j.ctrv.2010.03.002. Epub 2010 Mar 23.

    PubMed 20334979

  • 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.

    PubMed 16971718

  • 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.

    PubMed 17008704

  • 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.

    PubMed 19269519

  • 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.

    PubMed 26643092

  • 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.

    PubMed 27059037

  • 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.

    PubMed 12924450

  • Cunningham D, Zalcberg J, Maroun J, James R, Clarke S, Maughan TS, Vincent M, Schulz J, Gonzalez Baron M, Facchini T. Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. a review of phase II/III trials. Eur J Cancer. 2002 Mar;38(4):478-86. doi: 10.1016/s0959-8049(01)00413-0.

    PubMed 11872339

  • 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.

    PubMed 12044507

  • 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.

    PubMed 11597383

  • Valentini V, Coco C, Minsky BD, Gambacorta MA, Cosimelli M, Bellavita R, Morganti AG, La Torre G, Trodella L, Genovesi D, Portaluri M, Maurizi-Enrici R, Barbera F, Maranzano E, Lupattelli M. Randomized, multicenter, phase IIb study of preoperative chemoradiotherapy in T3 mid-distal rectal cancer: raltitrexed + oxaliplatin + radiotherapy versus cisplatin + 5-fluorouracil + radiotherapy. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):403-12. doi: 10.1016/j.ijrobp.2007.06.025. Epub 2007 Oct 4.

    PubMed 17919844

  • 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.

    PubMed 24418359

  • 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.

    PubMed 24078665

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Preoperative radiation, Raltitrexed and Pelvic surgery in people with Rectal Neoplasms Malignant, run by Chinese Academy of Medical Sciences at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-year disease-free survival probability (%) (time frame: 2 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02992886, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2021.

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