Clinical trial NCT02605265: Trial of Capecitabine With or Without Irinotecan Driven by UGT1A1
Official title: A Randomized Phase III Trial of Capecitabine With or Without Irinotecan Driven by UGT1A1 in Neoadjuvant Chemoradiation of Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Locally Advanced Rectal Cancer
Keywords: Neoadjuvant Chemoradiation
Irinotecan
UGT1A1
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital with Nanjing Medical University
name: Hubei Cancer Hospital
name: First Affiliated Hospital of Chongqing Medical University
name: Ruijin Hospital
First posted: 2015-11-16
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study evaluate the addition of Irinotecan in neoadjuvant chemoradiation. Half of participants will receive capecitabine alone together with neoadjuvant CRT, followed by a cycle of XELOX, while the other will receive capecitabine and irinotecan during CRT, followed by a cycle of XELIRI. All participants will be scheduled to receive surgery 6-8 weeks after the completion of CRT, then 5 cycles of adjuvant chemotherapy of XELOX.


Eligibility criteria: Inclusion Criteria:

* pathological confirmed adenocarcinoma
* clinical stage T3-4 and/or N+
* the distance from anal verge less than 12 cm
* without distance metastases
* KPS \>=70
* UGT1A1\*28 6/6 or 6/7
* without previous anti-cancer therapy
* sign the inform consent

Exclusion Criteria:

* pregnancy or breast-feeding women
* serious medical illness
* baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10\^9/L, Hb≥90g/L, PLT≥100×10\^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
* DPD deficiency
* UGT1A1\*28 7/7

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: Surgery scheduled 6-8 weeks after the end of chemoradiation
Secondary outcomes:
measure: Overall Survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
measure: Disease-free Survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 years
measure: Local Control rate
timeFrame: From date of randomization until the date of first documented pelvic failure, assessed up to 10 years
measure: Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to 2 years
measure: Surgical complications
timeFrame: Surgery scheduled 6-8 weeks after the end of chemotherapy
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhen Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang X, Fan J, Zhang L, Wang J, Wang M, Zhu J. Association Between Three-Dimensional Transrectal Ultrasound Findings and Tumor Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: An Observational Study. Front Oncol. 2021 Jun 4;11:648839. doi: 10.3389/fonc.2021.648839. eCollection 2021.
citation: Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. doi: 10.1200/JCO.20.01932. Epub 2020 Oct 29.
citation: Yao Y, Xu X, Yang L, Zhu J, Wan J, Shen L, Xia F, Fu G, Deng Y, Pan M, Guo Q, Gao X, Li Y, Rao X, Zhou Y, Liang L, Wang Y, Zhang J, Zhang H, Li G, Zhang L, Peng J, Cai S, Hu C, Gao J, Clevers H, Zhang Z, Hua G. Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer. Cell Stem Cell. 2020 Jan 2;26(1):17-26.e6. doi: 10.1016/j.stem.2019.10.010. Epub 2019 Nov 21.
citation: Guan Y, Shen Y, Xu Y, Li C, Wang J, Gu W, Lian P, Huang D, Cai S, Zhang Z, Zhu J. An expansion study of genotype-driven weekly irinotecan and capecitabine in combination with neoadjuvant radiotherapy for locally advanced rectal cancer with UGT1A1 *1*1 genotype. Therap Adv Gastroenterol. 2019 Jun 6;12:1756284819852293. doi: 10.1177/1756284819852293. eCollection 2019.