NCT03042000

Brief Summary

At present, the combined modality treatment of preoperative neoadjuvant chemoradiotherapy (NCRT) followed by radical surgery has become the standard of care for the locally advanced mid/low rectal cancer, having been proved to substantially improve the local control of the disease, whereas not being able to improve the long-term survival. According to present clinical practice guidelines, all patients with cT3-4N0M0 or cTanyN1-2M0 mid/low rectal cancer are recommended to undergo the preoperative long-term radiotherapy with concurrent 5FU based chemotherapy, followed by the radical resection of the tumor. After surgery, adjuvant chemotherapy (ACT) is recommended for all these patients without considering the postoperative pathological results. Recently, however, some authors proposed that different strategy of combined modality therapy should be applied in different patients according to their risk of relapse, instead of using the uniform NCRT strategy. In this research, on the basis of investigator's previous clinical practice and researches, investigators plan to stratify the patients with cT3-4N0M0 or cTanyN1-2M0 mid/low rectal cancer into several subgroups according to tumor stages and the risk of relapse. Different therapeutic strategy will be applied in different groups, at the aim of improving the overall therapeutic effects, as well as reducing the treatment adverse effects. This research consists of four trials.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,200

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Feb 2017

Longer than P75 for not_applicable

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2017

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

February 2, 2017

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 3, 2017

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2021

Completed
Last Updated

February 3, 2017

Status Verified

February 1, 2017

Enrollment Period

3.8 years

First QC Date

February 2, 2017

Last Update Submit

February 2, 2017

Conditions

Rectal Cancer, AdenocarcinomaNeoadjuvant Chemoradiation

Keywords

rectal cancerneoadjuvant chemoradiationcirculating tumor DNAlocal recurrencelong-term survival

Outcome Measures

Primary Outcomes (1)

  • 3y-DFS

    the 3-year disease free survival rate

    3 years

Secondary Outcomes (4)

  • 3y-OS

    3 years

  • 5y-DFS

    5 years

  • 5y-OS

    5 years

  • pCR

    4 months

Study Arms (6)

Group A1

EXPERIMENTAL

Patients with cT3a-bN0-1aM0 mid rectal cancer who undergo the treatment modality of 'radical surgery + adjuvant chemotherapy (ACT)'

Other: non-NCRT

Group A2

ACTIVE COMPARATOR

Patients with cT3a-bN0-1aM0 mid rectal cancer who undergo the treatment modality of 'NCRT + radical surgery + ACT'

Other: NCRT

Group B1

EXPERIMENTAL

Patients with cT4NanyM0 or cTanyN2M0 mid/low rectal cancer who undergo the treatment modality of 'NCRT with combined chemotherapy (Capox regimen) + radical surgery + ACT'

Drug: capecitabine with oxaliplatin

Group B2

ACTIVE COMPARATOR

Patients with cT4NanyM0 or cTanyN2M0 mid/low rectal cancer who undergo the treatment modality of 'NCRT with single-agent chemotherapy (Capecitabine) + radical surgery + ACT'

Drug: capecitabine

Group C1

EXPERIMENTAL

Patients with locally advanced rectal cancer, being clinically staged cCR after NCRT, who undergo the transanal endoscopic microsurgery (TEM) excision of the lesion.

Procedure: TEM

Group C2

ACTIVE COMPARATOR

Patients with locally advanced rectal cancer, being clinically staged cCR after NCRT, who undergo the radical resection of the lesion.

Procedure: radical resection

Interventions

non-NCRTOTHER

without the preoperative concurrent chemoradiothearpy (no neoadjuvant chemoradiation)

Group A1
NCRTOTHER

the preoperative concurrent chemoradiothearpy (neoadjuvant chemoradiation)

Group A2
capecitabine with oxaliplatinDRUG

combined chemotherapy with capecitabine with oxaliplatin

Group B1
capecitabineDRUG

single-agent chemotherapy with capecitabine

Group B2
TEMPROCEDURE

transanal endoscopic microsurgery (TEM) excision of the lesion

Group C1
radical resectionPROCEDURE

radical resection of rectal cancer

Group C2

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients aged 18 to 75 years old. Patients with cT3-4N0M0 or cTanyN+M0 mid/low rectal cancer. Patients with ASA physical status scroe of I to III. Patients who can fully understand the content of the informed consent form and sign it upon their own opinions.
  • Patients who can coordinate with the researchers to undergo the long-term post-treatment rechecks and follow-ups.

You may not qualify if:

  • Patient has any underlying or current medical condition, which, in the opinion of the Investigator, would interfere with the evaluation of the patient (e.g., end-stage liver disease, pulmonary hypertension, systemic lupus erythematosis etc.).
  • Patient is pregnant or lactating. Patient has a history of malignancy within 5 years except curatively treated basal cell carcinoma, squamous cell carcinoma in a non-mucosal, ultraviolet exposed area, or cervical carcinoma.
  • Patient is participating in any other clinical trials within 30 days prior to screening.
  • Patient has severe mental illness. Patient has any other conditions, which, in the opinion of the Investigator, would interfere with the evaluation of the subject.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (11)

  • Zhou J, Qiu H, Lin G, Xiao Y, Wu B, Wu W, Sun X, Lu J, Zhang G, Xu L, Liu Y. Is adjuvant chemotherapy necessary for patients with pathological complete response after neoadjuvant chemoradiotherapy and radical surgery in locally advanced rectal cancer? Long-term analysis of 40 ypCR patients at a single center. Int J Colorectal Dis. 2016 Jun;31(6):1163-8. doi: 10.1007/s00384-016-2579-5. Epub 2016 Apr 5.

    PMID: 27044403BACKGROUND

  • Ferrari L, Fichera A. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer. Gastroenterol Rep (Oxf). 2015 Nov;3(4):277-88. doi: 10.1093/gastro/gov039. Epub 2015 Aug 19.

    PMID: 26290512BACKGROUND

  • Breugom AJ, Swets M, Bosset JF, Collette L, Sainato A, Cionini L, Glynne-Jones R, Counsell N, Bastiaannet E, van den Broek CB, Liefers GJ, Putter H, van de Velde CJ. Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015 Feb;16(2):200-7. doi: 10.1016/S1470-2045(14)71199-4. Epub 2015 Jan 12.

    PMID: 25589192BACKGROUND

  • Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavere P, Glanzmann C, Cellier P, Collette L; EORTC Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. doi: 10.1016/S1470-2045(13)70599-0. Epub 2014 Jan 17.

    PMID: 24440473BACKGROUND

  • Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013 Mar 29;339(6127):1546-58. doi: 10.1126/science.1235122.

    PMID: 23539594BACKGROUND

  • Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.

    PMID: 24553385BACKGROUND

  • Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013 Mar 28;368(13):1199-209. doi: 10.1056/NEJMoa1213261. Epub 2013 Mar 13.

    PMID: 23484797BACKGROUND

  • Zhou J, Chang L, Guan Y, Yang L, Xia X, Cui L, Yi X, Lin G. Application of Circulating Tumor DNA as a Non-Invasive Tool for Monitoring the Progression of Colorectal Cancer. PLoS One. 2016 Jul 26;11(7):e0159708. doi: 10.1371/journal.pone.0159708. eCollection 2016.

    PMID: 27459628BACKGROUND

  • Reinert T, Scholer LV, Thomsen R, Tobiasen H, Vang S, Nordentoft I, Lamy P, Kannerup AS, Mortensen FV, Stribolt K, Hamilton-Dutoit S, Nielsen HJ, Laurberg S, Pallisgaard N, Pedersen JS, Orntoft TF, Andersen CL. Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery. Gut. 2016 Apr;65(4):625-34. doi: 10.1136/gutjnl-2014-308859. Epub 2015 Feb 4.

    PMID: 25654990BACKGROUND

  • Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.

    PMID: 27384348BACKGROUND

  • Jung KU, Kim HC, Park JO, Park YS, Park HC, Choi DH, Cho YB, Yun SH, Lee WY, Chun HK. Adjuvant chemotherapy after neoadjuvant chemoradiation and curative resection for rectal cancer: is it necessary for all patients? J Surg Oncol. 2015 Mar 15;111(4):439-44. doi: 10.1002/jso.23835. Epub 2014 Dec 9.

    PMID: 25488390BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

CapecitabineOxaliplatin

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesCoordination ComplexesOrganic Chemicals

Central Study Contacts

Jiaolin Zhou, MD.

CONTACT

8613910136704conniezhjl@163.com

Guole Lin, MD.

CONTACT

861069152211linglpumch@163.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

February 2, 2017

First Posted

February 3, 2017

Study Start

February 1, 2017

Primary Completion

December 1, 2020

Study Completion

December 1, 2021

Last Updated

February 3, 2017

Record last verified: 2017-02