Back to resultsPD-1 Inhibitors Combined With VEGF Inhibitors for Locally Advanced dMMR/MSI-H Colorectal Cancer
Primary Purpose
Colorectal Cancer, Microsatellite Instability High
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PD-1 inhibitor plus VEGF inhibitors
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Locally confirmed dMMR or MSI-H colorectal carcinoma
- Tumor staging based on CT/MR or transrectal ultrasound imaging:
- Colon cancer: radiological high risk (rT4 or rT3 tumour with extramural extension ≥ 5mm with or without lymph node involvement)
- Rectal cancer: <12 cm from the anal verge and radiological high risk (rT3/4 with or without lymph node involvement)
- No sign of bowel obstruction, or bowel obstruction has been relieved by ostomy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
- Aged 18 or over
- Life expectancy of at least 2 years
- Measurable disease
- Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose
- Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose
- Adequate organ function
Exclusion Criteria:
- Active autoimmune disease that has required systemic treatment in past 2 years
- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to this study start
- Currently participating and receiving treatment in another study within 4 weeks of study start
- History of severe allergic reaction to monoclonal antibody
- Strong evidence of distant metastases or peritoneal nodules (M1)
- Colonic obstruction that has not been defunctioned
- Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.) or anti-VEGF agents (e.g., Bevacizumab, Apatinib)
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%
- Received a live vaccine within 30 days of planned start of study medication
- Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C
- Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
- Known history of active tuberculosis (Bacillus tuberculosis [TB])
- Active infection requiring systemic therapy
Sites / Locations
- 651 Dongfeng Road East
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PD-1 inhibitors plus VEGF inhibitors
Arm Description
Patients will be given 4 cycles of Camrelizumab (200mg iv every 3 weeks) plus Apatinib (250mg QD day1-14) before being evaluated for response.
Outcomes
Primary Outcome Measures
Clinical complete response or pathological complete response
Clinical complete response or immunotherapy-related pathological complete response (cCR or immunotherapy-related pCR)
Secondary Outcome Measures
Objective Response Rate (ORR, PR+CR)
3-year relapse-free survival
3-year overall survival
Surgical complications
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Full Information
NCT ID
NCT04715633
First Posted
January 13, 2021
Last Updated
January 28, 2023
Sponsor
Sun Yat-sen University
Collaborators
Guangdong Provincial People's Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine
1. Study Identification
Unique Protocol Identification Number
NCT04715633
Brief Title
PD-1 Inhibitors Combined With VEGF Inhibitors for Locally Advanced dMMR/MSI-H Colorectal Cancer
Official Title
PD-1 Inhibitors (Camrelizumab) Combined With VEGF Inhibitors (Apatinib) for Locally Advanced dMMR/MSI-H Colorectal Cancer: an Open-label, Multi-center, Phase II Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 1, 2020 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
Guangdong Provincial People's Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this open-label phase II study, patients will be scheduled for neoadjuvant treatment with PD-1 inhibitors (Camrelizumab) plus VEGF inhibitor (Apatinib) for dMMR/MSI-H colorectal cancer staged as locally advanced (cT3-4N+/-M0 for rectal cancer, cT4 or cT3 with extramural extension ≥5mm for colon cancer). Radiological evaluation will be preformed after 4 cycles of treatment. Patients (either with colon or rectal cancer) who achieve complete clinical response will be offered the choice of Watch & Wait.
Detailed Description
This is an open-label phase II study, with the aim of determining the efficacy of PD-1 inhibitors (Camrelizumab) plus VEGF inhibitor (Apatinib) as a neoadjuvant therapy for dMMR/MSI-H locally advanced colorectal cancer.
Patients will be evaluated for eligibility within 14 days prior to study initiation with CT (for colon cancer) and/or MRI (for rectal cancer).
Patients will be given four cycles of Camrelizumab (200mg iv every 3 weeks) plus Apatinib (250mg QD day1-14) before being evaluated for response. For patients with colon cancer, if a SD/PD is achieved and the tumor is deemed unresectable, they will be offered chemotherapy±radiotherapy, while if a CR or PR is achieved, they will be offered another four cycles of Camrelizumab + Apatinib. After completing 8 cycles of treatment, if a CR is achieved they will be offered the choice of Watch & Wait. For patients with rectal cancer who have a SD/PD (after 4 cycles), chemoradiotherapy will be offered, while for those with a CR/PR, another four cycles of the treatment will be given. After completing 8 cycles of treatment, if a CR is achieved patients will be offered the choice of Watch & Wait.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Microsatellite Instability High
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PD-1 inhibitors plus VEGF inhibitors
Arm Type
Experimental
Arm Description
Patients will be given 4 cycles of Camrelizumab (200mg iv every 3 weeks) plus Apatinib (250mg QD day1-14) before being evaluated for response.
Intervention Type
Drug
Intervention Name(s)
PD-1 inhibitor plus VEGF inhibitors
Other Intervention Name(s)
Camrelizumab plus Apatinib
Intervention Description
Camrelizumab 200mg IV every 3 weeks; Apatinib 250mg QD day 1-14. Rescue chemotherapy: Oxaliplatin 130mg/m2 IV drip Q3W d1+Capecitabine 1000mg/m2 QD d1-d14 Rescue chemoradiotherapy: Long-course radiotherapy +Capecitabine 825mg/m2 QD d1-d14
Primary Outcome Measure Information:
Title
Clinical complete response or pathological complete response
Description
Clinical complete response or immunotherapy-related pathological complete response (cCR or immunotherapy-related pCR)
Time Frame
up to 2 year
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR, PR+CR)
Time Frame
up to 2 year
Title
3-year relapse-free survival
Time Frame
up to 3 years
Title
3-year overall survival
Time Frame
up to 3 years
Title
Surgical complications
Time Frame
within 1 month after surgery
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
up to 2 year
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:
Locally confirmed dMMR or MSI-H colorectal carcinoma
Tumor staging based on CT/MR or transrectal ultrasound imaging:
Colon cancer: radiological high risk (rT4 or rT3 tumour with extramural extension ≥ 5mm with or without lymph node involvement)
Rectal cancer: <12 cm from the anal verge and radiological high risk (rT3/4 with or without lymph node involvement)
No sign of bowel obstruction, or bowel obstruction has been relieved by ostomy
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
Aged 18 or over
Life expectancy of at least 2 years
Measurable disease
Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose
Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 120 days after the last PD-1 antibody dose
Adequate organ function
Exclusion Criteria:
Active autoimmune disease that has required systemic treatment in past 2 years
Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to this study start
Currently participating and receiving treatment in another study within 4 weeks of study start
History of severe allergic reaction to monoclonal antibody
Strong evidence of distant metastases or peritoneal nodules (M1)
Colonic obstruction that has not been defunctioned
Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.) or anti-VEGF agents (e.g., Bevacizumab, Apatinib)
Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%
Received a live vaccine within 30 days of planned start of study medication
Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C
Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
Known history of active tuberculosis (Bacillus tuberculosis [TB])
Active infection requiring systemic therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pei-Rong Ding, M.D.
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
651 Dongfeng Road East
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
PD-1 Inhibitors Combined With VEGF Inhibitors for Locally Advanced dMMR/MSI-H Colorectal Cancer
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