Trial of Capecitabine With or Without Irinotecan Driven by UGT1A1 (CinClare)

• ClinicalTrials.gov Identifier: NCT02605265
• Recruitment Status: Unknown
• First Posted: November 16, 2015
• Last Update Posted: December 7, 2016
• Sponsor: Fudan University
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Hubei Cancer Hospital; First Affiliated Hospital of Chongqing Medical University; Ruijin Hospital
• Information provided by (Responsible Party): Zhen Zhang, Fudan University

Tracking Information

• First Submitted Date: November 9, 2015
• First Posted Date: November 16, 2015
• Last Update Posted Date: December 7, 2016
• Study Start Date: October 2015
• Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 13, 2015): Pathologic Complete Response [ Time Frame: Surgery scheduled 6-8 weeks after the end of chemoradiation ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 14, 2015)

• Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 10 years ]
• Disease-free Survival [ Time Frame: 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 ]
• Local Control rate [ Time Frame: From date of randomization until the date of first documented pelvic failure, assessed up to 10 years ]
  Number of participants with pelvic failure after surgery, evaluated using Kaplan-Meier Curve
• Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 2 years ]
• Surgical complications [ Time Frame: Surgery scheduled 6-8 weeks after the end of chemotherapy ]

Original Secondary Outcome Measures (submitted: November 13, 2015)

• Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 10 years ]
• Disease-free Survival [ Time Frame: 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 ]
• Local Control rate [ Time Frame: From date of randomization until the date of first documented pelvic failure, assessed up to 10 years ]
  Number of participants with pelvic failure after surgery, evaluated using Kaplan-Meier Curve
• Toxicity related to chemoradiation (Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0) [ Time Frame: Up to 2 years ]
  Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0
• Surgical complications [ Time Frame: Surgery scheduled 6-8 weeks after the end of chemotherapy ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Locally Advanced Rectal Cancer

Intervention

• Radiation: Radiation
  Pelvic Radiation: 50Gy/25Fx
• Drug: Capecitabine
  Other Name: Xeloda
• Drug: Irinotecan
  Other Name: CPT-11
• Drug: Oxaliplatin

Study Arms

• Active Comparator: Capecitabine Alone

  Concurrent Chemoradiotherapy:

  Radiation: 50Gy/25Fx; Capecitabine: 825mg/m2 bid Monday-Friday per week

  Chemotherapy in Interval Between CRT and Surgery:

  Capecitabine: 1000mg/m2 bid d1-14; Oxaliplatin: 130mg/m2 d1

  Surgery:

  Scheduled 6-8 weeks after the completion of CRT

  Adjuvant Chemotherapy:

  Capecitabine: 1000mg/m2 bid d1-14; Oxaliplatin: 130mg/m2 d1; q3w, 5cycles

  Interventions:

  • Radiation: Radiation
  • Drug: Capecitabine
  • Drug: Oxaliplatin
• Experimental: Capecitabine with Irinotecan

  Concurrent Chemoradiotherapy:

  Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)

  Chemotherapy in Interval Between CRT and Surgery:

  Capecitabine: 1000mg/m2 bid d1-14; Irinotecan: 200mg/m2 d1

  Surgery:

  Scheduled 6-8 weeks after the completion of CRT

  Adjuvant Chemotherapy:

  Capecitabine: 1000mg/m2 bid d1-14; Oxaliplatin: 130mg/m2 d1; q3w, 5cycles

  Interventions:

  • Radiation: Radiation
  • Drug: Capecitabine
  • Drug: Irinotecan
  • Drug: Oxaliplatin

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 24, 2015): 360
• Original Estimated Enrollment (submitted: November 13, 2015): 242
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02605265
• Other Study ID Numbers: FDRT-R005
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Zhen Zhang, Fudan University
• Original Responsible Party: Same as current
• Current Study Sponsor: Fudan University
• Original Study Sponsor: Same as current

Collaborators

• The First Affiliated Hospital with Nanjing Medical University
• Hubei Cancer Hospital
• First Affiliated Hospital of Chongqing Medical University
• Ruijin Hospital

Investigators

• Principal Investigator: Zhen Zhang, MD; Fudan University

• PRS Account: Fudan University
• Verification Date: December 2016