Clinical trial NCT04411524: The Combination of Immunotherapy and Neoadjuvant Chemoradiotherapy in MSI-H Locally Advanced Rectal Cancer
Official title: A Phase II Trial of Immunotherapy Combined With Neoadjuvant Chemoradiotherapy in Microsatellite Instability-High Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-06-02
Enrollment: 50
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. pregnancy or breast-feeding women
2. history of other malignancies within 5 years
3. serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
4. immunodeficiency disease or long-term using of immunosuppressive agents
5. 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
6. DPD deficiency
7. UGT1A1\*28 7/7
8. the MSI status is MSS or p-MMR
9. allergic to any component of the therapy

Primary outcomes:
measure: Pathologic Complete Response Rate
timeFrame: The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy.
Secondary outcomes:
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 36 months.
measure: Local recurrence free survival
timeFrame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 36 months.
measure: Adverse effects
timeFrame: From date of randomization until the date of death from any cause, assessed up to 5 years
measure: Surgical complications
timeFrame: 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.
measure: Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life.
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
measure: Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life.
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
measure: Quality of Life Scale, range 0-60. It evaluates the quality of life from 12 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhen Zhang
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhen Zhang, M.D, PH.D
role: PRINCIPAL_INVESTIGATOR
References: