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Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer

Primary Purpose

Locally Advanced Rectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
AK104
Capecitabine
Neoadjuvant Radiotherapy
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Rectal Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18-75 ECOG 0-1 Rectal adenocarcinoma cT3-4aNany or cT1-4aN+ No distant metastasis Location ≤15 cm from the anal verge the MSI status is MSS and pMMR Sufficient bone marrow, kidney and liver function No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy Exclusion Criteria: bowel obstruction Distant metastasis Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV ) Uncontrollable severe hypertesion Active severe infection Cachexia, organ dysfunction Previous pelvic radiotherapy or chemotherapy Multiple primary cancers Epileptic seizures Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma Persons deprived of liberty or under guardianship Impossibility for compliance to follow-up Certain or suspicious allergy to research drug Pregnant or breast-feeding woman

Sites / Locations

  • Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage.

Outcomes

Primary Outcome Measures

Complete response (CR) rate
Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).

Secondary Outcome Measures

Adverse effects
Adverse effects according to CTCAE 5.0
Rate of Major pathologic response and tumor regression grade distribution
Rate of Major pathologic response and tumor regression grade distribution
Rate of surgical complications
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Disease free survival
3 year disease free survival rate
Local recurrence free survival
3 year local recurrence free survival rate
Overall survival
5 year overall survival rate
Long-term anal function
Long-term anal function was evaluated using the Wexner Continence Grading Scale ,the score being calculated after the patients' completion of a daily defecatory questionnaire. Range is from 0 (normal continence) to 20 (maximum incontinence with maximum disturbance of lifestyle)

Full Information

First Posted
July 26, 2023
Last Updated
October 24, 2023
Sponsor
Sun Yat-sen University
Collaborators
Akeso, Haplox Biotechnology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05980689
Brief Title
Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer
Official Title
A Phase II Trial of AK104 Combined With Neoadjuvant Chemoradiotherapy in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 24, 2023 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
January 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
Akeso, Haplox Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is an open-label, single-arm study to investigate the efficacy and safety of AK104 (an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) and neoadjuvant chemoradiotherapy in patients with pMMR/MSS locally advanced rectal cancer.
Detailed Description
The study evaluates the addition of AK104(an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) in neoadjuvant chemoradiotherapy in proficient Mismatch Repair (pMMR) /Microsatellite Stable (MSS) locally advanced rectal cancer (LARC). A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage. The tumor response to treatment, adverse effects and long-term prognosis will be analyzed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Rectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage.
Intervention Type
Drug
Intervention Name(s)
AK104
Other Intervention Name(s)
Cadonilimab
Intervention Description
During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
During neo-CRT: 825mg/m2 bid Monday-Friday per week
Intervention Type
Radiation
Intervention Name(s)
Neoadjuvant Radiotherapy
Intervention Description
IMRT DT: 50Gy/25Fx
Primary Outcome Measure Information:
Title
Complete response (CR) rate
Description
Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).
Time Frame
an average of 6 months.
Secondary Outcome Measure Information:
Title
Adverse effects
Description
Adverse effects according to CTCAE 5.0
Time Frame
From date of randomization until the date of death from any cause, assessed up to 5 years
Title
Rate of Major pathologic response and tumor regression grade distribution
Description
Rate of Major pathologic response and tumor regression grade distribution
Time Frame
an average of 1 year.
Title
Rate of surgical complications
Description
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Time Frame
The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 1 year from the surgery.
Title
Disease free survival
Description
3 year disease free survival rate
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 36 months.
Title
Local recurrence free survival
Description
3 year local recurrence free survival rate
Time Frame
From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Title
Overall survival
Description
5 year overall survival rate
Time Frame
From date of randomization until the date of death from any cause, assessed up to 60 months.
Title
Long-term anal function
Description
Long-term anal function was evaluated using the Wexner Continence Grading Scale ,the score being calculated after the patients' completion of a daily defecatory questionnaire. Range is from 0 (normal continence) to 20 (maximum incontinence with maximum disturbance of lifestyle)
Time Frame
1.5 year after diagnosis

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-75 ECOG 0-1 Rectal adenocarcinoma cT3-4aNany or cT1-4aN+ No distant metastasis Location ≤15 cm from the anal verge the MSI status is MSS and pMMR Sufficient bone marrow, kidney and liver function No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy Exclusion Criteria: bowel obstruction Distant metastasis Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV ) Uncontrollable severe hypertesion Active severe infection Cachexia, organ dysfunction Previous pelvic radiotherapy or chemotherapy Multiple primary cancers Epileptic seizures Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma Persons deprived of liberty or under guardianship Impossibility for compliance to follow-up Certain or suspicious allergy to research drug Pregnant or breast-feeding woman
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
WeiWei Xiao
Phone
8613710390520
Ext
8613710390520
Email
xiaoww@sysucc.org.cn
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
WeiWei xiao
Phone
8613710390520
Ext
8613710390520
Email
xiaoww@sysucc.org.cn

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer

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