Radiation-protection Effect of Amifostine in Locally Advanced Rectal Cancer

Sponsor

Fudan University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03702985

Collaborator

(none)

160

Enrollment

Location

Arms

21.1

Anticipated Duration (Months)

7.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study evaluates the addition of Amifostine to capecitabine and irinotecan in neoadjuvant chemoradiation(CRT) in locally advanced rectal cancer. Half of participants will receive capecitabine and along with neoadjuvant radiotherapy, followed by a cycle of XELIRI, while the others will receive capecitabine and irinotecan added by amifostine 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 it will depends which regimens the patient would receive according to his or her pathological results.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer	Radiation: Radiation Drug: Capecitabine Drug: Irinotecan Drug: Amifostine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase II Trial of Capecitabine and Irinotecan With or Without Amifostine in Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Actual Study Start Date :

May 28, 2018

Anticipated Primary Completion Date :

Nov 1, 2019

Anticipated Study Completion Date :

Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Capecitabine and Irinotecan without Amifostine Concurrent Chemoradiotherapy: Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A128 6/6) or 65mg/m2 (UGT1A128 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: depends on patients pathological review.	Radiation: Radiation Pelvic Radiation: 50Gy/25Fx Drug: Capecitabine 625mg/m2 bid Monday-Friday per week Other Names: Xeloda Drug: Irinotecan 80mg/m2 (UGT1A128 6/6) or 65mg/m2 (UGT1A128 6/7)
Experimental: Capecitabine and Irinotecan with Amifostine Concurrent Chemoradiotherapy: Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A128 6/6) or 65mg/m2 (UGT1A128 6/7) Amifostine: 400mg/m2 per week 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: depends on patients pathological review.	Radiation: Radiation Pelvic Radiation: 50Gy/25Fx Drug: Capecitabine 625mg/m2 bid Monday-Friday per week Other Names: Xeloda Drug: Irinotecan 80mg/m2 (UGT1A128 6/6) or 65mg/m2 (UGT1A128 6/7) Drug: Amifostine 400mg/m2 per week

Arm

Intervention/Treatment

Active Comparator: Capecitabine and Irinotecan without Amifostine

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: depends on patients pathological review.

Radiation: Radiation

Pelvic Radiation: 50Gy/25Fx

Drug: Capecitabine

625mg/m2 bid Monday-Friday per week

Other Names:

Xeloda

Drug: Irinotecan

80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)

Experimental: Capecitabine and Irinotecan with Amifostine

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) Amifostine: 400mg/m2 per week 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: depends on patients pathological review.

Radiation: Radiation

Pelvic Radiation: 50Gy/25Fx

Drug: Capecitabine

625mg/m2 bid Monday-Friday per week

Other Names:

Xeloda

Drug: Irinotecan

80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)

Drug: Amifostine

400mg/m2 per week

Outcome Measures

Primary Outcome Measures

the morbidity of hematological adverse events and diarrhea as assessed by CTCAE v4.0 [during neoadjuvant chemoradiation.]

Secondary Outcome Measures

Impact of participants' quality of life during treatment as assessed by EQ-5D questionnaire and EORTC-QLQ-C30 questionnaire [during neoadjuvant chemoradiation.]
pathological response rate [Surgery scheduled 6-8 weeks after the end of chemoradiation.]
the morbidity of late radiation proctitis [late radiation proctitis is measured 9 months after the end of chemoradiation.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

pathological confirmed adenocarcinoma
clinical stage T3-4 and/or N+
the distance from anal verge less than 12 cm
without distance metastases
performance status score: 0~1
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