The Combination of Immunotherapy and Neoadjuvant Chemoradiotherapy in MSI-H Locally Advanced Rectal Cancer

NCT04411524 | Unknown Phase 2

• 1 other identifier: FDRT-2019-104-1734
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The study evaluates the addition of immunotherapy of PD-1 antibody in neoadjuvant chemoradiotherapy in microsatellite stability-high (MSI-H) locally advanced rectal cancer (LARC). A total of 50 MSI-H LARC patients will receive 2 cycles of PD-1 antibody, followed by capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3 cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of adjuvant chemotherapy of XELOX. The tumor response grade, adverse effects and long-term prognosis will be analyzed.

Conditions

Locally Advanced Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate

  Pathologic Complete Response Rate

  The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy.

Secondary Outcomes (8)

• Disease free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.

• Local recurrence free survival

  From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.

• Overall survival

  From date of randomization until the date of death from any cause, assessed up to 36 months.

• Adverse effects

  From date of randomization until the date of death from any cause, assessed up to 5 years

• Surgical complications

  The surgery was scheduled 7-8 weeks after the end of chemoradiotherapy. And the surgical complications were assessed up to 5 years from the surgery.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

A total of 50 MSI-H LARC patients will receive 2 cycles of PD-1 antibody, followed by capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3 cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of adjuvant chemotherapy of XELOX.

Drug: PD-1 antibody; Drug: Capecitabine; Drug: Irinotecan; Radiation: Neoadjuvant Radiotherapy

Interventions

PD-1 antibody DRUG

Before neo-CRT: 2 cycles of PD-1 antibody After neo-CRT: 3 cycles of PD-1 antibody

Treatment Arm

Capecitabine DRUG

During neo-CRT: 625mg/m2 bid Monday-Friday per week

Also known as: Xeloda

Treatment Arm

Irinotecan DRUG

During neo-CRT: 80mg/m2 qw (UGT1A1\*28 6/6) or 65mg/m2 qw (UGT1A1\*28 6/7)

Treatment Arm

Neoadjuvant Radiotherapy RADIATION

IMRT DT: 50Gy/25Fx

Treatment Arm

Eligibility Criteria

• Age: 15 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• pathological confirmed adenocarcinoma
• clinical stage T3-4 and/or N+
• the distance from anal verge less than 12 cm
• without distance metastases
• age 18-70 years old, female and male
• KPS \>=70
• UGT1A1\*28 6/6 or 6/7
• the MSI status is MSI-H or d-MMR
• without previous anti-cancer therapy or immunotherapy
• with good compliance
• signed the inform consent

You may not qualify if:

• pregnancy or breast-feeding women
• history of other malignancies within 5 years
• serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
• immunodeficiency disease or long-term using of immunosuppressive agents
• 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
• the MSI status is MSS or p-MMR
• allergic to any component of the therapy

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Zhen Zhang

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Interventions

spartalizumab; Capecitabine; Irinotecan; Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Combined Modality Therapy; Therapeutics

Study Officials

• Zhen Zhang, M.D, PH.D

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Zhang, M.D, PH.D

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 10, 2020
• First Posted: June 2, 2020
• Study Start: July 1, 2020
• Primary Completion: April 30, 2022
• Study Completion: December 31, 2022
• Last Updated: June 2, 2020

Record last verified: 2020-05

Locations

CN (1)