Trifluridine/Tipiracil (TAS-102) With or Without Thalidomide for the Treatment of Metastatic Colorectal Cancer

March 4, 2022 updated by: Fujian Cancer Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Fuzhou, China
        • Not yet recruiting
        • First Affiliated Hospital of Fujian Medical University
        • Contact:
          • Rixiong Rixiong Wang
      • Fuzhou, China
        • Not yet recruiting
        • Fujian Provincial People's Hospital
        • Contact:
          • Wujin Chen
      • Fuzhou, China
        • Not yet recruiting
        • Fuzhou First Hospital affiliated to Fujian Medical University
        • Contact:
          • Jingrong Liu
      • Fuzhou, China
        • Not yet recruiting
        • Hospital 900 of the Joint Logistic Support Force of the Chinese People's Liberation Army
        • Contact:
          • Fangwei Xie
      • Fuzhou, China
        • Not yet recruiting
        • The Third People's Hospital affiliated to Fujian University of Chinese Medicine
        • Contact:
          • Wenwu Wang
    • Fujian
      • Fuzhou, Fujian, China
        • Recruiting
        • Fujian Medical University Cancer Hospital, Fujian Cancer Hospital
        • Contact:
          • Zengqing Zengqing Guo
          • Phone Number: +86 13860603879
          • Email: gzq_005@126.com

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 to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  1. Have histological or cytological documentation of adenocarcinoma of the colon or rectum (mCRC).
  2. 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.
  3. 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:

  1. Platelet count ≥75 × 109 /L
  2. Hemoglobin level ≥90 g/L
  3. 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

  1. 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.
  2. 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.
  3. Peripheral neuropathy > grade 1 (adverse events per CTCAE v5.0).
  4. History of uncontrolled or medicated heart disease.
  5. Seizure disorder requiring medication.
  6. Known history of human immunodeficiency virus (HIV) infection.
  7. Patients with an active infection.
  8. Other uncontrolled concurrent diseases determined by the researchers as not meeting the study conditions.
  9. Patients with ascites and pleural effusion with clinical symptoms requiring treatment.
  10. Known allergy to any of the study drug ingredients.
  11. Unable to swallow oral medication.
  12. Prior exposure to TAS-102 or thalidomide.
  13. Patients who have brain metastases.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TAS-102+Thalidomide
Thalidomide 100mg PO BID+TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
Drug: Thalidomide
For the experimental group, the intervention was thalidomide（100mg PO Bid)
Other Names:
  • Thalidomide Tablets produced by Changzhou Pharmaceutical Factory Co. LTD
Drug: TAS-102
TAS-102
Active Comparator: TAS-102
TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
Drug: TAS-102
TAS-102

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
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
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.
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 Measures

Outcome Measure
Measure Description
Time Frame
Overall survival（OS）
Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
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.
From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
Incidence of Treatment-Emergent Adverse Events
Time Frame: from first dose to within 30 days after the last dose
Incidence of Treatment-Emergent Adverse Events were evaluated in accordance with the NCI CTC AE Version 5.0
from first dose to within 30 days after the last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fujian Cancer Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

October 1, 2021

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

January 13, 2022

First Submitted That Met QC Criteria

February 23, 2022

First Posted (Actual)

March 4, 2022

Study Record Updates

Last Update Posted (Actual)

March 18, 2022

Last Update Submitted That Met QC Criteria

March 4, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TACTIC

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.

Clinical Trials on Metastatic Colorectal Cancer

Clinical Trials on Thalidomide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kenya

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe