A Clinical trial to analysis of immune profile following neoadjuvant chemotherapy in colorectal liver metastases patients
- Conditions
- Neoplasms
- Registration Number
- KCT0003474
- Lead Sponsor
- Asan Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 20
1.Have provided written informed consent prior to any study specific procedures
2.Willing and able to comply with the protocol
3.= 20 years of age at the time of signing Informed Consent Form
4.Eastern Cooperative Oncology Group (ECOG) status of =1
1.Histologically diagnosed colorectal adenocarcinoma
2.Liver metastases from colorectal adenocarcinoma confirmed through biopsy
3.Liver metastatic lesions should be considered to be potentially resectable after conversion chemotherapy by multi-disciplinary team and should meet one of the following criteria:
?- Number of metastatic deposit >=4
?- Possibility of resection margin could be involved
?- Involvement of major hepatic vessels
?- Presence of extrahepatic metastases (if they are supposed to be treated with curative aim and not to alter a plan for hepatic metastasectomy)
?- High likelihood of insufficient residual hepatic volume after surgery
4.Measurable by RECIST criteria 1.1.
5.One or more hepatic lesions should be accessible for biopsy
6.Archival tumor tissue from the metastatic liver lesion obtained at the time of the initial diagnosis must be available.
7.Adequate major organ functions as following:
?-Hematopoietic function: ANC >= 1,500/mm3, Platelet >= 100,000/mm3
?-Hepatic function: serum bilirubin <= 2 x ULN, AST/ALT levels <= 5 x ULN
?-Renal function: serum creatinine <= 1.5 x ULN
8.INR < 1.5 or aPTT < 1.5 x ULN within 14 days prior to the start of study treatment for patients not receiving anti-coagulation. For patients receiving anticoagulants, INR and aPTT must be within the medical standard of enrolling institution.
1.For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of ? 1% per year during the treatment period and for 6 months after the last dose of study treatment after the last dose of study treatment
i.A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
ii.Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
2.For men, they must practice abstinence or condom use, and abstain from sperm donation during the treatment period and for 6 months after their last dose of study treatment.
1.Extrahepatic metastases that are not candidates for treatment of curative aim (e.g. resection, radiation or radiofrequency ablation)
2.Presence of central nervous system (CNS) metastases
3.Concurrent or previous history of another primary cancer within 3 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanomatous skin cancer, superficial bladder cancer (pTis or pT1) and curatively treated thyroid cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer without distant metastasis could be allowed with the agreement of the principal investigator.
4.Chronic alcoholic hepatitis or cirrhosis
5.Chronic hepatitis B, defined as HBV DNA (> 2,000 IU / mL) and ALT> upper limit of normal range, must be treated with antiviral drugs before enrollment to reach appropriate viral suppression (HBV DNA <2000 IU / mL), and the antiviral drugs must be maintained during the study treatment period and for 6 months after the last dose of study treatment.
6.Prior chemotherapy for metastatic disease
7.Uncontrolled medical illness congestive heart failure, myocardial infarction within 6 months including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months
8.Prior adjuvant FOLFOX chemotherapy
9.Prior adjuvant chemotherapy, if administered within 6 months before study entry
10.Current or recent (within 10 days of start of study treatment) use of aspirin (>325mg/day), clopidogrel (>75mg/day), therapeutic or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (therapeutic anticoagulation on a stable dose for at least 2 weeks prior to the start of study treatment is allowed)
11.Known alcohol or drug abuse
12.Active infection requiring intravenous antibiotics at the start of study treatment
13.Inadequately controlled hypertension (defined as systolic blood pressure >150mmHg and/or diastolic blood pressure >100mmHg)
14.Prior history of hypertensive crisis or hypertensive encephalopathy
15.History or evidence upon physical or neurological examination of CNS disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
16.Uncontrolled chronic peripheral neuropathy = CTCAE grade 2
17.Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study treatment
18.Any previous venous thromboembolism > CTCAE Grade 3 within 12 months prior to start of study treatment
19.History of haemoptysis = Grade 2 (defined as = 2.5 mL bright red blood per episode) within 1 month of start of study treatment
20.History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation)
21.Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to start of study treatment, or anticipation of need for major surgical procedure (other than hepatic metastasectomy) during the course of the study
22.History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to start of study treatment
23.Serious, non-healing wound, active ulcer, or untreated bone fracture
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Serial changes in Cluster of Differentiation(CD) 8+ T cell densities
- Secondary Outcome Measures
Name Time Method Serial changes of Immune cell biomarkers CD3, CD4, Programmed death-Ligand 1(PD-L1),PD-1, granzyme B, CD45RO, Forkhead Box P3(FOXP3), CD68;Serial changes of Immune cell CD3+, CD8+ densities;Serial changes of Density of Vascular marker CD31, CD34 - Opal(TM) platform IHC;Serial changes of Gene expression profile - RNA-seq;Response Rate - RECIST 1.1 and immune RECIST(iRECIST);Progression-Free Survival;R0 resection rate;Incidence, nature and severity of adverse events with severity (Safety profile) - Common Terminology Criteria for Adverse Events (CTCAE) v4.0;Microbiome profile - In stool samples through whole metagenomic sequencing