Back to resultsTrifluridine/Tipiracil (TAS-102) With or Without Thalidomide for the Treatment of Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Thalidomide
TAS-102
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
Eligibility Criteria
- Have histological or cytological documentation of adenocarcinoma of the colon or rectum (mCRC).
- For patients with disease progression after conventional treatment, TAS-102 is determined as the third-line therapy or beyond according to the routine treatment practice of the researcher.
- Aged no less than 20 years.
5.Have a measurable disease, according to RECIST version 1.1 6.Eastern Cooperative Oncology Group performance status 0-2. 7.Life expectancy of at least 12 weeks. 8.For women with reproductive potential, serum tests were performed within 7 days before the start of study treatment β- Human chorionic gonadotropin (β- HCG) pregnancy test, the result is negative. Women with reproductive potential must agree to take appropriate contraceptive measures with informed consent until at least 6 months after the last use of the study drug.
9.Sufficient bone marrow, liver and kidney functions and meet the following laboratory requirements:
- Platelet count ≥75 × 109 /L
- Hemoglobin level ≥90 g/L
- Absolute neutrophil count ≥1.5× 109 /L
a) Total bilirubin ≤1.5 × upper limit of normal (ULN) b) Alanine aminotransferase and aspartate aminotransferase ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) d) Serum creatinine ≤1.5 × ULN e) Glomerular filtration rate ≥30 ml/min/1.73 m2, according to the modified diet in renal disease abbreviated formula 10.Able to take oral drugs. 11.Have signed written informed consent.
Exclusion criteria
- With arterial or venous thrombosis or embolic events such as myocardial infarction, cerebral thrombosis, intracerebral hemorrhage, deep venous thrombosis or pulmonary embolism within 6 months before the start of the study.
- Evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event ≥ grade 3 (adverse events per CTCAE v5.0) within 4 weeks prior to the start of treatment.
- Peripheral neuropathy > grade 1 (adverse events per CTCAE v5.0).
- History of uncontrolled or medicated heart disease.
- Seizure disorder requiring medication.
- Known history of human immunodeficiency virus (HIV) infection.
- Patients with an active infection.
- Other uncontrolled concurrent diseases determined by the researchers as not meeting the study conditions.
- Patients with ascites and pleural effusion with clinical symptoms requiring treatment.
- Known allergy to any of the study drug ingredients.
- Unable to swallow oral medication.
- Prior exposure to TAS-102 or thalidomide.
- Patients who have brain metastases.
Sites / Locations
- Fujian Medical University Cancer Hospital, Fujian Cancer HospitalRecruiting
- First Affiliated Hospital of Fujian Medical University
- Fujian Provincial people's Hospital
- Fuzhou First Hospital affiliated to Fujian Medical University
- Hospital 900 of the Joint Logistic Support Force of the Chinese People's Liberation Army
- The Third People's Hospital affiliated to Fujian University of Chinese Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
TAS-102+Thalidomide
TAS-102
Arm Description
Thalidomide 100mg PO BID+TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
Outcomes
Primary Outcome Measures
Progression-free survival (PFS)
PFS was defined as the time from randomization until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first.
Secondary Outcome Measures
Overall survival（OS）
OS was defined as the time from the date of randomization to the date of death due to any cause. For subjects who were alive or lost to follow-up by the data analysis cut-off date, survival was censored at the subject's last known survival time.
Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment-Emergent Adverse Events were evaluated in accordance with the NCI CTC AE Version 5.0
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05266820
Brief Title
Trifluridine/Tipiracil (TAS-102) With or Without Thalidomide for the Treatment of Metastatic Colorectal Cancer
Official Title
TACTIC: a Phase II Study of TAS-102 Monotherapy and Thalidomide Plus TAS-102 as Third-line Therapy and Beyond in Patients With Advanced Colorectal Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fujian Cancer Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Thalidomide has both anti-angiogenesis and antiemetic effects, and its combined use with TAS-102 may reduce the gastrointestinal reactions associated with TAS-102, while enhancing antitumor efficacy and reducing the side effects of chemotherapy, and its cost is significantly lower than that of bevacizumab, which has higher pharmacoeconomics and greater clinical research application value.
Detailed Description
In the past decade, the use of targeted drugs has greatly improved the overall survival of patients with mCRC. However, there are currently few effective drugs available clinically. Trifluridine/Tipiracil (TAS-102) is a novel cytotoxic antitumor drug taken orally with minor adverse reactions, consisting of trifluridine and tipyrimidine hydrochloride. Tas-102 has been approved for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF biological therapy; and if RAS wild type, an anti-EGFR therapy. Multiple studies have shown that TAS-102 prolongs median OS and PFS in mCRC patients compared with placebo.
Thalidomide is a sedative that was developed in the late 1950s and eventually marketed and prescribed in several countries to pregnant women to alleviate nausea in the late 1950s and early 1960s. The drug, however, caused severe birth defects in more than 10,000 children worldwide and was forced to withdraw from the international market. Further studies found that the S-optical isomer of thalidomide can inhibit neutrophil chemotaxis, produce anti-inflammatory activity, stimulate immune system activation, regulate immunity, anti-angiogenesis, and inhibit the adhesion of cancer cells to stroma, so as to change the microenvironment of the body, and achieve anti-tumor effect.
Thalidomide has both anti-angiogenesis and antiemetic effects, and its combined use with TAS-102 may reduce the gastrointestinal reactions associated with TAS-102, while enhancing antitumor efficacy and reducing the side effects of chemotherapy, and its cost is significantly lower than that of bevacizumab, which has higher pharmacoeconomics and greater clinical research application value.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TAS-102+Thalidomide
Arm Type
Experimental
Arm Description
Thalidomide 100mg PO BID+TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
Arm Title
TAS-102
Arm Type
Active Comparator
Arm Description
TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Other Intervention Name(s)
Thalidomide Tablets produced by Changzhou Pharmaceutical Factory Co. LTD
Intervention Description
For the experimental group, the intervention was thalidomide（100mg PO Bid)
Intervention Type
Drug
Intervention Name(s)
TAS-102
Intervention Description
TAS-102
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
PFS was defined as the time from randomization until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first.
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Secondary Outcome Measure Information:
Title
Overall survival（OS）
Description
OS was defined as the time from the date of randomization to the date of death due to any cause. For subjects who were alive or lost to follow-up by the data analysis cut-off date, survival was censored at the subject's last known survival time.
Time Frame
From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
Title
Incidence of Treatment-Emergent Adverse Events
Description
Incidence of Treatment-Emergent Adverse Events were evaluated in accordance with the NCI CTC AE Version 5.0
Time Frame
from first dose to within 30 days after the last dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Have histological or cytological documentation of adenocarcinoma of the colon or rectum (mCRC).
For patients with disease progression after conventional treatment, TAS-102 is determined as the third-line therapy or beyond according to the routine treatment practice of the researcher.
Aged no less than 20 years.
5.Have a measurable disease, according to RECIST version 1.1 6.Eastern Cooperative Oncology Group performance status 0-2. 7.Life expectancy of at least 12 weeks. 8.For women with reproductive potential, serum tests were performed within 7 days before the start of study treatment β- Human chorionic gonadotropin (β- HCG) pregnancy test, the result is negative. Women with reproductive potential must agree to take appropriate contraceptive measures with informed consent until at least 6 months after the last use of the study drug.
9.Sufficient bone marrow, liver and kidney functions and meet the following laboratory requirements:
Platelet count ≥75 × 109 /L
Hemoglobin level ≥90 g/L
Absolute neutrophil count ≥1.5× 109 /L
a) Total bilirubin ≤1.5 × upper limit of normal (ULN) b) Alanine aminotransferase and aspartate aminotransferase ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) d) Serum creatinine ≤1.5 × ULN e) Glomerular filtration rate ≥30 ml/min/1.73 m2, according to the modified diet in renal disease abbreviated formula 10.Able to take oral drugs. 11.Have signed written informed consent.
Exclusion criteria
With arterial or venous thrombosis or embolic events such as myocardial infarction, cerebral thrombosis, intracerebral hemorrhage, deep venous thrombosis or pulmonary embolism within 6 months before the start of the study.
Evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event ≥ grade 3 (adverse events per CTCAE v5.0) within 4 weeks prior to the start of treatment.
Peripheral neuropathy > grade 1 (adverse events per CTCAE v5.0).
History of uncontrolled or medicated heart disease.
Seizure disorder requiring medication.
Known history of human immunodeficiency virus (HIV) infection.
Patients with an active infection.
Other uncontrolled concurrent diseases determined by the researchers as not meeting the study conditions.
Patients with ascites and pleural effusion with clinical symptoms requiring treatment.
Known allergy to any of the study drug ingredients.
Unable to swallow oral medication.
Prior exposure to TAS-102 or thalidomide.
Patients who have brain metastases.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zengqing Guo
Phone
+86 13860603879
Email
gzq_005@126.com
Facility Information:
Facility Name
Fujian Medical University Cancer Hospital, Fujian Cancer Hospital
City
Fuzhou
State/Province
Fujian
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zengqing Zengqing Guo
Phone
+86 13860603879
Email
gzq_005@126.com
Facility Name
First Affiliated Hospital of Fujian Medical University
City
Fuzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rixiong Rixiong Wang
Facility Name
Fujian Provincial people's Hospital
City
Fuzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wujin Chen
Facility Name
Fuzhou First Hospital affiliated to Fujian Medical University
City
Fuzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jingrong Liu
Facility Name
Hospital 900 of the Joint Logistic Support Force of the Chinese People's Liberation Army
City
Fuzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fangwei Xie
Facility Name
The Third People's Hospital affiliated to Fujian University of Chinese Medicine
City
Fuzhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenwu Wang
12. IPD Sharing Statement
Plan to Share IPD
No
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Trifluridine/Tipiracil (TAS-102) With or Without Thalidomide for the Treatment of Metastatic Colorectal Cancer
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