FMT Combined With Immune Checkpoint Inhibitor and TKI in the Treatment of CRC Patients With Advanced Stage
Primary Purpose
Colorectal Neoplasms Malignant
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Fecal microbiota transplantation plus Sintilimab and Fruquintinib
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms Malignant focused on measuring Gastrointestinal Microbiome
Eligibility Criteria
Inclusion Criteria:
- Sign the informed consent form.
- Metastatic or locally advanced colorectal adenocarcinoma unresectable or unfit for radical radiochemotherapy confirmed by pathology or cytology.
- Microsatellite stable or pMMR patients failed standard treatment, including platinum, irinotecan, fluorouracil and Bevacizumab (Ras and BRAF wt patients should recived Cetuximab).
- Patients have at least one lesion could be evaluated by RECIST v1.1 or mRECIST.
- The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1.
- The life expectancy is more than 3 months.
- Good organ function:
Blood routine: hemoglobin ≥90g/L, white blood cell ≥3.0×10^9/L, neutrophil ≥1.5×10^9/L, platelet ≥100×10^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥60ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL, ALT≤5×UNL and AST≤5×UNL for patients with liver metastasis.
Exclusion Criteria:
- Have received any anti-PD-1, anti-PD-L1/L2 antibodies, anti-CTLA-4 antibodies and other immunotherapy in the past.
- Have received any TKI therapy in the past.
- Clinically significant ascites.
- Known to have allergic reactions to any ingredients or excipients of experimental drugs.
- Have received any antibiotics within 28 days before the first medication or any probiotics or prebiotics within 14 days before the first medication.
- Radiotherapy, RFA, interventional therapy or surgery were performed within 28 days before the first medication (except for previous diagnostic biopsy).
- Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment.
- Brain metastasis or meningeal metastasis has been confirmed. Patients with neurological symptoms should receive brain CT / MRI examination to exclude metastasis.
- Patients who is suffering from intestinal obstruction, gastrointestinal bleeding, pulmonary fibrosis or interstitial pneumonia, renal failure, liver failure or cerebrovascular disease.
- Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug.
- Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months.
- Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C.
- Suffering from autoimmune diseases or history of organ transplantation requiring immunosuppressive therapy.
- May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results.
- Pregnant women (determined by serum human chorionic gonadotropin [hCG]) or lactating women, or plan to conceive during the treatment period, 2 months after cetuximab treatment and 6 months after capecitabine treatment. Women of childbearing age with positive or no pregnancy test at baseline. Women of childbearing age or sexually active men were not willing to use contraception during the study period, at least 2 months after cetuximab treatment and 6 months after capecitabine treatment. Postmenopausal women must be amenorrhea for at least 12 months to be considered infertile.
- There are other serious diseases that the researchers believe patients cannot be included in the study
Sites / Locations
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
FMT
Arm Description
Fecal microbiota transplantation plus Sintilimab and Fruquintinib
Outcomes
Primary Outcome Measures
ORR
Objective Response Rate
Secondary Outcome Measures
OS
Overall Survival
PFS
Progression Free Survival
Adverse events
Safety and tolerance
Full Information
NCT ID
NCT05279677
First Posted
March 5, 2022
Last Updated
August 21, 2022
Sponsor
Chinese Academy of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT05279677
Brief Title
FMT Combined With Immune Checkpoint Inhibitor and TKI in the Treatment of CRC Patients With Advanced Stage
Official Title
Phase II, Single-arm Study of FMT Combined With Immune Checkpoint Inhibitor and TKI in the Treatment of Colorectal Cancer Patients With Advanced Stage
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 12, 2022 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
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
A single-arm, phase II study was designed to evaluate the efficacy and safety of fecal microbiota transplantation plus Sintilimab and Fruquintinib as the later line treatment in colorectal patients with advanced stages.
Detailed Description
The combination of regorafenib plus nivolumab had already presented a manageable safety profile and encouraging antitumor activity in patients with mCRC as the REGONIVO trail reported. While additional investigations showed limited ORRs between 7%-33% as third or later line treatement in mCRC. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for the treatment of CRC. The individualized gut microbiome transplantation may further imrpove the efficacy of the combination therapy of CPI and TKI. Thus, a single-arm, phase II study was designed to evaluate the efficacy and safety of FMT plus Sintilimab and Fruquintinib as the later line treatment in CRC patients with advanced stages.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms Malignant
Keywords
Gastrointestinal Microbiome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
FMT
Arm Type
Experimental
Arm Description
Fecal microbiota transplantation plus Sintilimab and Fruquintinib
Intervention Type
Drug
Intervention Name(s)
Fecal microbiota transplantation plus Sintilimab and Fruquintinib
Intervention Description
Microbiota capsules containing 1g gut microbiota, po d1-3 before anti-tumor treatment, total for 8 cycles.
Sintilimab 200mg iv, q3w. Fruquintinib 5mg po d1-14, q3w.
Primary Outcome Measure Information:
Title
ORR
Description
Objective Response Rate
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
OS
Description
Overall Survival
Time Frame
Up to 2 years
Title
PFS
Description
Progression Free Survival
Time Frame
Up to 2 years
Title
Adverse events
Description
Safety and tolerance
Time Frame
Up to 2 years
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:
Sign the informed consent form.
Metastatic or locally advanced colorectal adenocarcinoma unresectable or unfit for radical radiochemotherapy confirmed by pathology or cytology.
Microsatellite stable or pMMR patients failed standard treatment, including platinum, irinotecan, fluorouracil and Bevacizumab (Ras and BRAF wt patients should recived Cetuximab).
Patients have at least one lesion could be evaluated by RECIST v1.1 or mRECIST.
The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1.
The life expectancy is more than 3 months.
Good organ function:
Blood routine: hemoglobin ≥90g/L, white blood cell ≥3.0×10^9/L, neutrophil ≥1.5×10^9/L, platelet ≥100×10^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥60ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL, ALT≤5×UNL and AST≤5×UNL for patients with liver metastasis.
Exclusion Criteria:
Have received any anti-PD-1, anti-PD-L1/L2 antibodies, anti-CTLA-4 antibodies and other immunotherapy in the past.
Have received any TKI therapy in the past.
Clinically significant ascites.
Known to have allergic reactions to any ingredients or excipients of experimental drugs.
Have received any antibiotics within 28 days before the first medication or any probiotics or prebiotics within 14 days before the first medication.
Radiotherapy, RFA, interventional therapy or surgery were performed within 28 days before the first medication (except for previous diagnostic biopsy).
Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment.
Brain metastasis or meningeal metastasis has been confirmed. Patients with neurological symptoms should receive brain CT / MRI examination to exclude metastasis.
Patients who is suffering from intestinal obstruction, gastrointestinal bleeding, pulmonary fibrosis or interstitial pneumonia, renal failure, liver failure or cerebrovascular disease.
Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug.
Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months.
Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C.
Suffering from autoimmune diseases or history of organ transplantation requiring immunosuppressive therapy.
May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results.
Pregnant women (determined by serum human chorionic gonadotropin [hCG]) or lactating women, or plan to conceive during the treatment period, 2 months after cetuximab treatment and 6 months after capecitabine treatment. Women of childbearing age with positive or no pregnancy test at baseline. Women of childbearing age or sexually active men were not willing to use contraception during the study period, at least 2 months after cetuximab treatment and 6 months after capecitabine treatment. Postmenopausal women must be amenorrhea for at least 12 months to be considered infertile.
There are other serious diseases that the researchers believe patients cannot be included in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aiping Zhou, MD
Phone
86 13691161998
Email
zhouap1825@126.com
Facility Information:
Facility Name
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aiping Zhou, MD
Phone
+86 13691161998
Email
zhouap1825@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
FMT Combined With Immune Checkpoint Inhibitor and TKI in the Treatment of CRC Patients With Advanced Stage
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