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

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ClinicalTrials.gov Identifier: NCT05980689
Recruitment Status : Recruiting
First Posted : August 8, 2023
Last Update Posted : February 7, 2024
Sponsor:
Collaborators:
Akeso
Haplox Biotechnology Co., Ltd.
Information provided by (Responsible Party):
WeiWei Xiao, Sun Yat-sen University

Tracking Information
First Submitted Date  ICMJE July 26, 2023
First Posted Date  ICMJE August 8, 2023
Last Update Posted Date February 7, 2024
Actual Study Start Date  ICMJE October 24, 2023
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2023)		 Complete response (CR) rate [ Time Frame: an average of 6 months. ]
Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2023)
  • Adverse effects [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 5 years ]
    Adverse effects according to CTCAE 5.0
  • Rate of Major pathologic response and tumor regression grade distribution [ Time Frame: an average of 1 year. ]
    Rate of Major pathologic response and tumor regression grade distribution
  • Rate of surgical complications [ 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. ]
    Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
  • 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 36 months. ]
    3 year disease free survival rate
  • Local recurrence free survival [ Time Frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. ]
    3 year local recurrence free survival rate
  • Overall survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 months. ]
    5 year overall survival rate
  • Long-term anal function [ Time Frame: 1.5 year after diagnosis ]
    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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer
Official Title  ICMJE A Phase II Trial of AK104 Combined With Neoadjuvant Chemoradiotherapy in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced Rectal Cancer
Intervention  ICMJE
  • Drug: AK104
    During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.
    Other Name: Cadonilimab
  • Drug: Capecitabine
    During neo-CRT: 825mg/m2 bid Monday-Friday per week
  • Radiation: Neoadjuvant Radiotherapy
    IMRT DT: 50Gy/25Fx
Study Arms  ICMJE Experimental: Treatment Arm
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.
Interventions:
  • Drug: AK104
  • Drug: Capecitabine
  • Radiation: Neoadjuvant Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 5, 2023)		 33
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2025
Estimated Primary Completion Date June 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age 18-75
  2. ECOG 0-1
  3. Rectal adenocarcinoma
  4. cT3-4aNany or cT1-4aN+
  5. No distant metastasis
  6. Location ≤12 cm from the anal verge
  7. Positive PD-L1 expression (PD-L1 TPS≥1% or PD-L1 CPS ≥1)
  8. the MSI status is MSS and pMMR
  9. Sufficient bone marrow, kidney and liver function
  10. No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy

Exclusion Criteria:

  1. bowel obstruction
  2. Distant metastasis
  3. Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )
  4. Uncontrollable severe hypertesion
  5. Active severe infection
  6. Cachexia, organ dysfunction
  7. Previous pelvic radiotherapy or chemotherapy
  8. Multiple primary cancers
  9. Epileptic seizures
  10. Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma
  11. Persons deprived of liberty or under guardianship
  12. Impossibility for compliance to follow-up
  13. Certain or suspicious allergy to research drug
  14. Pregnant or breast-feeding woman
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: WeiWei Xiao 8613710390520 ext 8613710390520 xiaoww@sysucc.org.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05980689
Other Study ID Numbers  ICMJE B2022-766-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party WeiWei Xiao, Sun Yat-sen University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Sun Yat-sen University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Akeso
  • Haplox Biotechnology Co., Ltd.
Investigators  ICMJE Not Provided
PRS Account Sun Yat-sen University
Verification Date February 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP