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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Locally Advanced Rectal Cancer	Radiation: Radiation; Drug: Capecitabine; Drug: Irinotecan; Drug: Oxaliplatin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: October 2015
• Estimated Primary Completion Date: December 2017
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
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	Radiation: Radiation; Pelvic Radiation: 50Gy/25Fx; Drug: Capecitabine; Other Name: Xeloda; 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	Radiation: Radiation; Pelvic Radiation: 50Gy/25Fx; Drug: Capecitabine; Other Name: Xeloda; Drug: Irinotecan; Other Name: CPT-11; Drug: Oxaliplatin

Outcome Measures

Primary Outcome Measures :

1. Pathologic Complete Response [ Time Frame: Surgery scheduled 6-8 weeks after the end of chemoradiation ]

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 10 years ]
2. 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 ]
3. 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
4. Number of participants with chemoradiation-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 2 years ]
5. Surgical complications [ Time Frame: Surgery scheduled 6-8 weeks after the end of chemotherapy ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Ji Zhu, MD; +86-2164175590 ext 81607; leo.zhu@126.com

Locations

China, Shanghai

Fudan University Shanghai Cancer Center; Recruiting

Shanghai, Shanghai, China, 200032

Contact: Ji Zhu, MD leo.zhu@126.com

Principal Investigator: Zhen Zhang, MD

Sub-Investigator: Ji Zhu, MD

Sponsors and Collaborators

Fudan University

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Zhen Zhang, Professor, Fudan University
• ClinicalTrials.gov Identifier: NCT02605265
• Other Study ID Numbers: FDRT-R005
• First Posted: November 16, 2015
• Last Update Posted: December 7, 2016
• Last Verified: December 2016

Keywords provided by Zhen Zhang, Fudan University:

Neoadjuvant Chemoradiation; Irinotecan; UGT1A1

Additional relevant MeSH terms:

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Capecitabine; Oxaliplatin; Irinotecan; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors