Safety of Cetuximab and Trifluridin Tipiracil as the Third-line Therapy in the RASwt mCRC
Primary Purpose
Colorectal Neoplasms Malignant
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Cetuximab + trifluridin tipiracil
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms Malignant
Eligibility Criteria
Inclusion Criteria:
- 18-75 years old male or female;
- Histologically or cytologically confirmed metastatic colon or rectal adenocarcinoma; excluding appendiceal cancer and anal canal cancer;
- Previously received second-line treatment, at least 2 standard chemotherapy regimens(including fluorouracil, capecitabine, irinotecan, oxaliplatin, raltitrexed and anti-VEGF, anti-EGFR, etc.), if already accepted anti-EGFR treatment achieved at least PR or above;
- ECOG PS 0-1;
- At least one measurable lesion by CT or MRI (according to RECIST 1.1 criteria, the longest diameter of tumor lesion CT/MRI scan ≥ 10 mm, lymph node lesion CT/MRI scan shortest diameter ≥ 15 mm);
- RAS gene mutation detection results are wild-type. The test sample can be the primary tumor or metastasis sample;
- Can receive oral drug treatment;
Normal function of major organs, meeting the following criteria within 14 days before the start of treatment:
- neutrophil count ≥ 1.5 × 10*9/L;
- Platelet count ≥ 75 × 10*9/L;
- Hemoglobin ≥ 9.0 g/dL;
- AST ≤ 2.5 × UNL (upper limit of normal) (if liver metastasis AST ≤ 5 × UNL);
- ALT ≤ 2.5 × UNL (if liver metastasis AST ≤ 5 × UNL);
g.Creatinine clearance (calculated according to Cockcroft and Gault formula) > 60 mL/min or serum creatinine ≤ 1.5 × UNL;
- Expected survival time > 3 months (90 days);
- Women of childbearing potential must have used reliable contraception and had a negative pregnancy test within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial and for 6 months after the last dose of trial drug. Males must agree to use an adequate method of contraception or have been surgically sterilized during the trial and for 6 months after the last dose of trial drug;
- The patients voluntarily participated in this study and signed the informed consent form, with good compliance and cooperation in the follow-up.
Exclusion Criteria:
- Previously treated with regorafenib, fruquintinib, TAS-102;
- Participated in another drug clinical trial in the past 4 weeks, or received systemic chemotherapy, radiotherapy or biological therapy in the past 4 weeks;
- Known brain metastases or strongly suspected brain metastases;
- Patients with known BARF mutations should be excluded;
- Synchronous cancer or metachronous cancer with disease-free survival ≥ 5 years (except colorectal cancer), excluding mucosal cancer (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.) that has been cured or may be cured by local resection;
- Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and gastric intestinal obstruction; ucontrolled Crohn's disease or ulcerative colitis;
- Serosal effusion (including pleural effusion, ascites, pericardial effusion) with clinical symptoms and requiring symptomatic treatment;
- Pregnant or lactating women; patients of childbearing potential are unwilling or unable to take effective contraceptive measures;
- Known to be allergic to the study drug, study drug class and its ingredients;
- Conditions requiring systemic steroid treatment (except topical steroid and cetuximab pretreatment);
- History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or CT findings of interstitial lung disease;
- Active local or systemic infection requiring treatment;
- Cardiac function classification (NYHA classification) ≥ Grade III or severe heart disease;
- Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) or active hepatitis B, C;
- Toxicity not recovered (CTCAE > grade 1) or not completely recovered from previous anticancer surgery;
- Patients judged by the Investigator as unsuitable for this study.
Sites / Locations
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cetuximab and trifluridin tipiracil
Arm Description
Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; Or dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;
Outcomes
Primary Outcome Measures
Incidence of DLT(Dose-limited toxicity)
Determination of RP2D based on incidence of DLT
Secondary Outcome Measures
Adverse Eevents
Participants With Incidence of Adverse Eevents During Treatment Period
Full Information
NCT ID
NCT05155124
First Posted
December 7, 2021
Last Updated
September 9, 2022
Sponsor
Wuhan Union Hospital, China
1. Study Identification
Unique Protocol Identification Number
NCT05155124
Brief Title
Safety of Cetuximab and Trifluridin Tipiracil as the Third-line Therapy in the RASwt mCRC
Official Title
Safety of Cetuximab in Combination With Trifluridin Tipiracil in the Third-line Treatment of RASwt Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 2022 (Anticipated)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
April 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wuhan Union Hospital, China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
This was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (TAS-102) in the third-line treatment of Chinese patients with RAS wild-type mCRC.
Detailed Description
This was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (TAS-102) in the third-line treatment of Chinese patients with RAS wild-type mCRC. Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; after 1 cycle will be observed, and if ≤ 2 patients experience DLT, this dose level will be the recommended phase II dose; if ≥ 3 patients experience DLT, additional 6 patients will receive dose level 0. ( Dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;) If ≤ 2 individuals experience DLT, this dose level is the recommended Phase II dose; if ≥ 3 individuals experience DLT, the study will be stopped.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms Malignant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab and trifluridin tipiracil
Arm Type
Experimental
Arm Description
Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; Or dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;
Intervention Type
Drug
Intervention Name(s)
Cetuximab + trifluridin tipiracil
Other Intervention Name(s)
Erbitux;TAS102;TAS-102
Intervention Description
Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; Or dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;
Primary Outcome Measure Information:
Title
Incidence of DLT(Dose-limited toxicity)
Description
Determination of RP2D based on incidence of DLT
Time Frame
From Baseline to primary completion date, about 18 months
Secondary Outcome Measure Information:
Title
Adverse Eevents
Description
Participants With Incidence of Adverse Eevents During Treatment Period
Time Frame
From Baseline to primary completion date, about 18 months
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:
18-75 years old male or female;
Histologically or cytologically confirmed metastatic colon or rectal adenocarcinoma; excluding appendiceal cancer and anal canal cancer;
Previously received second-line treatment, at least 2 standard chemotherapy regimens(including fluorouracil, capecitabine, irinotecan, oxaliplatin, raltitrexed and anti-VEGF, anti-EGFR, etc.), if already accepted anti-EGFR treatment achieved at least PR or above;
ECOG PS 0-1;
At least one measurable lesion by CT or MRI (according to RECIST 1.1 criteria, the longest diameter of tumor lesion CT/MRI scan ≥ 10 mm, lymph node lesion CT/MRI scan shortest diameter ≥ 15 mm);
RAS gene mutation detection results are wild-type. The test sample can be the primary tumor or metastasis sample;
Can receive oral drug treatment;
Normal function of major organs, meeting the following criteria within 14 days before the start of treatment:
neutrophil count ≥ 1.5 × 10*9/L;
Platelet count ≥ 75 × 10*9/L;
Hemoglobin ≥ 9.0 g/dL;
AST ≤ 2.5 × UNL (upper limit of normal) (if liver metastasis AST ≤ 5 × UNL);
ALT ≤ 2.5 × UNL (if liver metastasis AST ≤ 5 × UNL);
g.Creatinine clearance (calculated according to Cockcroft and Gault formula) > 60 mL/min or serum creatinine ≤ 1.5 × UNL;
Expected survival time > 3 months (90 days);
Women of childbearing potential must have used reliable contraception and had a negative pregnancy test within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial and for 6 months after the last dose of trial drug. Males must agree to use an adequate method of contraception or have been surgically sterilized during the trial and for 6 months after the last dose of trial drug;
The patients voluntarily participated in this study and signed the informed consent form, with good compliance and cooperation in the follow-up.
Exclusion Criteria:
Previously treated with regorafenib, fruquintinib, TAS-102;
Participated in another drug clinical trial in the past 4 weeks, or received systemic chemotherapy, radiotherapy or biological therapy in the past 4 weeks;
Known brain metastases or strongly suspected brain metastases;
Patients with known BARF mutations should be excluded;
Synchronous cancer or metachronous cancer with disease-free survival ≥ 5 years (except colorectal cancer), excluding mucosal cancer (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.) that has been cured or may be cured by local resection;
Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and gastric intestinal obstruction; ucontrolled Crohn's disease or ulcerative colitis;
Serosal effusion (including pleural effusion, ascites, pericardial effusion) with clinical symptoms and requiring symptomatic treatment;
Pregnant or lactating women; patients of childbearing potential are unwilling or unable to take effective contraceptive measures;
Known to be allergic to the study drug, study drug class and its ingredients;
Conditions requiring systemic steroid treatment (except topical steroid and cetuximab pretreatment);
History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or CT findings of interstitial lung disease;
Active local or systemic infection requiring treatment;
Cardiac function classification (NYHA classification) ≥ Grade III or severe heart disease;
Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) or active hepatitis B, C;
Toxicity not recovered (CTCAE > grade 1) or not completely recovered from previous anticancer surgery;
Patients judged by the Investigator as unsuitable for this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hongli Liu, PhD
Phone
+86-027-85871962
Email
hongli_liu@hust.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Jieying Zhang, MD
Phone
+86-027-85871962
Email
whxhzjy@hust.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hongli Liu
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jieying Zhang
Phone
+8613554281983
Email
whxhzjy@hust.edu.cn
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety of Cetuximab and Trifluridin Tipiracil as the Third-line Therapy in the RASwt mCRC
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