- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05426811
Regorafenib Plus Raltitrexed as Third-line Treatment in Advanced Colorectal Cancer Patients
June 24, 2022 updated by: Yunpeng Liu, China Medical University, China
Regorafenib Plus Raltitrexed as Third-line Treatment in Advanced Colorectal Cancer Patients:An Open-label, Single-arm, Multicenter Phase I/II Study
This is a multicenter, open, single-arm, phase I/II study to evaluate the efficacy and safety of regorafenib plus raltitrexed as third-line treatment in patients with advanced colorectal cancer.
Study Overview
Status
Not yet recruiting
Intervention / Treatment
Detailed Description
This is a multicenter, open, single-arm, phase I/II study to evaluate the efficacy and safety of regorafenib plus raltitrexed as third-line treatment in patients with advanced colorectal cancer.This Phase Ib/II study consists of two parts, Phase Ib, an open-ended, single-arm, multi-centre, dose-escalation study evaluating regorafenib, and Phase II, an open-label, multi-centre study evaluating the efficacy and safety of regorafenib in combination with raltitrexed.The primary study endpoint: progression-free survival (PFS).The secondary end endpoints include ORR (overall effectiveness of tumour treatment),DCR (disease control rate),3 month/6 month/9 month/12 month survival OS%,OS (overall survival),incidence and severity of adverse events (AEs), serious adverse events (SAEs).
Study Type
Interventional
Enrollment (Anticipated)
50
Phase
- Phase 2
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria
- Sign a consent form
- Age> 18 years
- Pathological diagnosis as metastatic colorectal adenocarcinoma
- Metastatic colorectal cancer with disease progression after 1st and 2nd line treatment;Received standard chemotherapy based on fluorouracil, oxaliplatin, irinotecan, patients are allowed to receive EGFR and/or VEGF inhibitors, patients are allowed to receive immunotherapy.
- Measurable disease according to RECIST
- ECOG score 0-1 points
- Life expectancy ≥3 months
- ALT and AST< 2.5 times the upper limit of normal (ULN), patients with liver metastases < 5 times ULN
- Serum albumin ≥ 3.0g/ dL
- Serum ALP <2.5 times ULN
- Total bilirubin <l.5mg / dL
- Estimated creatinine clearance (CLcr) ≥30mL/min as calculated using the Cockcroft-Gault equation
- Lipase≤1.5x the ULN
- Neutrophil absolute count (ANC) ≥1500/mm³, hemoglobin (Hb)>9g/dl, platelets> 10000/mm³
- Pregnant or breastfeeding patients. (1) Women and men of childbearing potential must agree to use appropriate contraception prior to entering the program until at least 8 weeks after the last dose of study drug. The investigator or designee is required to advise the subject on how to achieve appropriate contraception. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) according to standard treatment 2) Women of childbearing age must confirm a negative serum or urine pregnancy test within 7 days prior to initiating treatment and must agree to record a negative result prior to entering the study
Exclusion criteria.
- Prior exposure to any VEGFR tyrosine kinase inhibitor (e.g., regorafenib, apatinib, anlotinib, furoquinitinib, etc.) therapy
- Received raltitrexed in the previous treatment
- Patients with abnormal coagulation function or those treated with thrombolytic or anticoagulant drugs with a tendency to bleed from the gastrointestinal tract, including active peptic ulcer with fecal occult blood ++, vomiting blood or black stool within 3 months
- Prior or concurrent cancers with a different primary site or histology than CRC within the enrollment year, except cured in situ cervical cancer, non-melanoma skin cancer, and superficial bladder tumors: staged Ta, Tis, and T1
- Arterial or venous thrombotic or embolic events such ascerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before the start of study medication (except for adequately treated catheter-related venous thrombos is occurring more than one month before the start of study medication)
- Major surgery, biopsy or significant traumatic damage within 28 days prior to the start of investigational treatment
- Non-healing wound, non-healing ulcer, or non-healing bone fracture.
- Patients with brain metastases and/or cancerous meningitis
- Congestive heart failure > New York Heart Association (NYHA) class 2.
- Unstable angina (angina symptoms at rest), new onset angina (occurred within the last 3 months). Myocardial infarction within 6 months prior to the start of treatment.
- Arrhythmias requiring antiarrhythmic therapy (beta-blockers or digoxin allowed)
- Uncontrolled hypertension. (Systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical treatment)
- Patients with pheochromocytoma
- Pleural effusion or ascites causing restricted breathing (≥ CTCAE grade 2 dyspnea)
- Known to have dihydropyrimidine dehydrogenase deficiency
- Ongoing infection > Grade 2 NCI CTCAE
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
- Known hypersensitivity to any of the stidy drugs, study drug classes,or excipients in the formulation
- The use of CYP3A4 inhibitors or inducers
- Participation in another clinical trial within 4 weeks prior to enrollment and receipt of the investigational drug and any concomitant therapy containing the investigational drug
- Received radiotherapy within 4 weeks prior to enrollment and the lesions observed in this study were in the target area of radiotherapy
- Subjects with active tuberculosis (TB) who are on anti-tuberculosis treatment, or who have received anti-tuberculosis treatment within one year prior to screening
- Comorbidities requiring long-term treatment with immunosuppressive drugs or systemic or topical corticosteroids at immunosuppressive doses (doses >10 mg/day of prednisone or other isotonic hormones)
- Received any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine, Neocon vaccine, etc.) within 4 weeks prior to enrollment
- Pregnancy or breastfeeding
- Persistent proteinuria >3.5g/24 hours by measuring the urine protein-creatinine ratio in random urine samples (grade 3, NCI-CTCAE version 5.0)
- Positive for Human Immunodeficiency Virus (HIV)
- Positive hepatitis B virus surface antigen (HBsAg) with positive HBV DNA copy number (quantitative test ≥ 1000 cps/ml)
- Positive blood screen for chronic hepatitis C (positive for HCV antibodies)
- Renal failure requiring hemodialysis or peritoneal dialysis
- The degree of dehydration ≥ CTCAE version 5.0 level 1
- Persons without legal capacity
- Any other clinically significant disease or condition that, in the opinion of the investigator, could affect compliance with the protocol, or affect the subject's ability to sign an informed consent form (ICF), or is inappropriate for participation in this clinical trial.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Regorafenib combined with Raltitrexed
Regorafenib: 120mg/d,Po,qd,d1-d21,Every 4 weeks Raltitrexed: 3mg/㎡,ivgtt,d1,Every 3 weeks |
Regorafenib:120mg/d,Po,qd,d1-d21,Every 4 weeks
Other Names:
Raltitrexed:3mg/㎡,ivgtt,d1,Every 3 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: one year
|
PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.
|
one year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: two years
|
Duration from the date of initial treatment to the date of death due to any cause.
|
two years
|
Objective Response Rate (ORR)
Time Frame: one year
|
ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
|
one year
|
Disease Control Rate (DCR)
Time Frame: one year
|
Determined using RECIST v1.1 criteria.
|
one year
|
Incidence and severity of adverse events (AE) and serious adverse events (SAE)
Time Frame: two years
|
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0.
|
two years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ANTICIPATED)
July 1, 2022
Primary Completion (ANTICIPATED)
July 1, 2025
Study Completion (ANTICIPATED)
December 30, 2025
Study Registration Dates
First Submitted
June 16, 2022
First Submitted That Met QC Criteria
June 16, 2022
First Posted (ACTUAL)
June 22, 2022
Study Record Updates
Last Update Posted (ACTUAL)
June 29, 2022
Last Update Submitted That Met QC Criteria
June 24, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Folic Acid Antagonists
- Raltitrexed
Other Study ID Numbers
- REGORAL
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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