mFOLFOX6 Combined With Dalpiciclib in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This is an prospective, single-center, single-arm, Simon's two-stage design, phase IIa study for advanced/metastatic colorectal cancer (CRC) who had failed or were intolerant to standard treatment. This study aims to evaluate the safety and efficacy of mFOLFOX6 combined with dalpiciclib (SHR6390) in the treatment of advanced/metastatic colorectal cancer.

Detailed Description
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Primary study end point: To evaluate the safety and objective response rate (ORR) of mFOLFOX6 combined with dalpiciclib (SHR6390) in patients with advanced/metastatic colorectal cancer who had failed or were intolerant to standard treatment. Secondary study end Point: To evaluate the progression-free survival (PFS) and overall survival (OS) of mFOLFOX6 combined with dalpiciclib (SHR6390) in patients with advanced/metastatic colorectal cancer who had failed or were intolerant to standard treatment.

Official Title
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mFOLFOX6 Combined With Dalpiciclib(SHR6390) in Patients With Metastatic Colorectal Cancer (FIND): A Single-arm, Phase IIa Study.

Conditions
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Advanced/Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Dalpiciclib
* Drug: Oxaliplatin injection
* Drug: Calcium folinate
* Drug: 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily sign informed consent Age: from 18 to 70 years old Definite histological evidence of colorectal adenocarcinoma ECOG 0-1 Advanced or metastatic colorectal cancer (AJCC/UICC stage IV) is confirmed by enhanced CT of the chest, abdomen and pelvis, with evaluable lesions Tumor progression or intolerable toxicity after previous standard treatment; Tumor progression during adjuvant therapy or within 6 months after completion of adjuvant therapy was considered as first-line treatment (Standard treatment must include all of the following drugs: fluorouracil, irinotecan, and oxaliplatin; With or without anti-VEGF monoclonal antibody (bevacizumab); Anti-EGFR treatment(cetuximab or panitumumab) in left colorectal RAS (KRAS/NRAS) wild-type subjects) The bone marrow, liver and kidney function satisfies the following conditions within 7 days before treatment (including day 7): Hemoglobin ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥75×109/L; aspartate aminotransferase (AST) ≤ 2 upper limit of normal (ULN), glutaminate alanine transaminase (ALT) ≤ 3 ULN, total bilirubin ≤ 1.5 ULN, serum creatinine ≤ 1.5 ULN Peripheral neurological lesions recover (≤ grade 1) before enrollment Subjects should not participate in other clinical trials during the study period Willing and able to comply with research procedures and follow-up plan Exclusion Criteria: Complicated with obstruction, active bleeding or perforation and requiring emergency surgery or stent placement Existing or coexisting other active malignancies Previously CDK inhibitors treatment Major surgery or severe trauma such as laparotomy, thoracotomy or laparoscopic organ removal within the previous 4 weeks Active coronary artery disease, severe/unstable angina or newly diagnosed angina or myocardial infarction in the past 12 months Thrombotic or embolic events occurred within the previous 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism or deep vein thrombosis New York Heart Association (NYHA) Class II or higher Congestive heart failure Presence of clinically symptomatic third space effusion (eg, massive pleural or ascites) that cannot be controlled by drainage or other methods Human immunodeficiency virus (HIV) infection or diseases associated with acquired immunodeficiency syndrome (AIDS) Active inflammatory bowel disease or other colorectal disease leading to chronic diarrhea Presence of CTCAE grade 2 or higher toxicity (other than anemia, alopecia and skin pigmentation) that has not recover due to any previous treatment Suspected allergies to any of the relevant drugs used in the study Pregnant or lactating Women of childbearing age (<2 years after last menstrual period) or men of childbearing potential not using or refusing to use effective non-hormonal contraception Any unstable medical condition that affects patient safety and study compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an prospective, single-center, single-arm, Simon's two-stage design, phase IIa study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mFOLFOX6 + dalpiciclib<br>Dalpiciclib is orally administered at 125mg qd for 21 days and discontinue for 7 days. mFOLFOX6 will be administered every 2 weeks. | Drug: Dalpiciclib<br>* Dalpiciclib is orally administered at 125mg qd for 21 days and discontinue for 7 days.<br>* Other names: SHR6390;Drug: Oxaliplatin injection<br>* 85mg/m², ivdrip, D1<br>* Other names: L-OHP;Drug: Calcium folinate<br>* 400mg/m², ivdrip, D1; or calcium levofolinate, 200 mg/m², ivdrip, D1<br>* Other names: Leucovorin;Drug: 5-fluorouracil<br>* 400mg/m², iv, D1; and 2400mg/m², civ, 46-48h<br>* Other names: Fluorouracil; 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Adverse Events) | The number of subjects who had adverse events and the type of adverse events were recorded according to CTCAE V.5.0. Safety failure was defined as any grade 3-5 treat-related adverse event (AE) (CTCAE 5.0) within 90 days from the date of the last regimen (whichever was reached later). | 1 year | 
| Objective Response Rate (ORR) | ORR was defined as the proportion of all subjects who received the study treatment and whose best overall response (BOR) was a complete response (CR) or a partial response (PR) according to RECIST version 1.1. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the date from enrollment to the first recorded of tumor progression (assessed by RECIST version 1.1) or the date of death from any cause, whichever came first. | 1 year | 
| Overall Survival (OS) | OS was defined as the date from enrollment to the date of death or the last follow-up. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, Dalpiciclib, Efficacy and safety