Skip to main content

Trifluridine and Tipiracil Hydrochloride and Stereotactic Body Radiation Therapy in Treating Patients with Colorectal Cancer with Liver Metastases

Trial Status: Active

This phase Ib / II trial studies the side effects and best dose of trifluridine and tipiracil hydrochloride when given together with stereotactic body radiation therapy and how well they work in treating patients with colorectal cancer that has spread to the liver. Trifluridine and tipiracil hydrochloride stops deoxyribonucleic acid (DNA) replication which may prevent cancer cells from growing. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving trifluridine and tipiracil hydrochloride and stereotactic body radiation therapy may work better in treating patients with colorectal cancer that has spread to the liver.

Inclusion Criteria

  • Participants must have biopsy-proven diagnosis of a colorectal cancer with 1-4 liver metastases; there is no upper size limit and participants must have at least 800 mL of uninvolved liver; liver metastases may be diagnosed by imaging alone, no liver biopsy is required; extrahepatic disease is allowed if 1) it has been stable for 3 months prior to study entry, 2) the dominant disease burden is intrahepatic and 3) the patient is referred for definitive radiation therapy to the disease in the liver
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with spiral computed tomography (CT) scan
  • Participants may have had prior chemotherapy, targeted biological therapy (i.e. sorafenib), surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as the prior therapy occurred more than 3 weeks before the first radiation treatment; patients may not have had prior liver directed radiation, including radioembolization
  • Expected survival must be greater than three months
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Participants must have liver metastases deemed unresectable due to anatomy, medical fitness, or presence of extrahepatic disease
  • History of transfusion is acceptable and transfusions may be given to meet eligibility requirements
  • Hemoglobin >= 9 g/dL
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 75,000/mm^3
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 X institutional upper limit of normal
  • Creatinine =< 1.5 mg/dl or creatinine clearance >= 60 mL/min/1.73 m^2 (calculated per Cockcroft & Gault formula) for subjects with creatinine levels above institutional normal
  • If patient has underlying cirrhosis, only Child-Pugh classification group A patients should be included in this study; clinical assessment of ascites and encephalopathy is required; Child-Pugh classification must be determined for all study participants at the time of eligibility analysis; as albumin and prothrombin time (PT)/international normalized ratio (INR) are required for Child-Pugh classification; these labs should be drawn with other labs required for eligibility analysis
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after stopping study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability to take oral medications (i.e. no feeding tube and able to swallow whole)

Exclusion Criteria

  • Women who are pregnant or lactating; patients must be either surgically sterile (via hysterectomy or bilateral tubal ligation), post-menopausal or using acceptable methods of contraception if they are of child bearing potential; female patients of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to starting drug; breastfeeding should be discontinued if the mother is treated with radiation
  • Participants with uncontrolled gross ascites or encephalopathy; assessment of ascites will be determined by the treating physician
  • Participants with local conditions or systemic illnesses that would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc
  • Participants who have had prior liver directed radiation treatment, including selective internal radiation (SIRspheres or Theraspheres)
  • Participants with a serious medical illness that may limit survival to less than 3 months
  • Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
  • Participants who are receiving any other investigational agents, or any other anti-cancer therapy during study treatment
  • Participants with any uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or serious psychiatric illness/social situations that would limit compliance with study requirements
  • Participants who have previously received TAS-102

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: ACTIVE
Contact: Theodore Sunki Hong
Phone: 617-726-6050

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of trifluridine and tipiracil hydrochloride (TAS-102) when given with stereotactic body radiation therapy (SBRT) to patients with hepatic metastases from colorectal cancer. (Phase I)

II. To demonstrate improvement over the historical one-year local control at one year (60%) by the addition of TAS-102 to SBRT for patients with hepatic metastases from colorectal cancer. (Phase II)

SECONDARY OBJECTIVES:

I. To assess safety and to characterize the potential toxicity of TAS-102 given in combination with SBRT to the liver in patients with hepatic metastases from colorectal cancer.

II. To determine progression-free survival associated with the addition of TAS-102 to SBRT to the liver for patients with hepatic metastases from colorectal cancer.

III. To determine overall survival associated with the addition of TAS-102 to SBRT to the liver for patients with hepatic metastases from colorectal cancer.

IV. To assess the correlation of KRAS or BRAF mutation status with local control, progression-free survival, and overall survival in patients with hepatic metastases from colorectal cancer who are receiving TAS-102 and SBRT to the liver.

V. To explore the utility of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) in patients with hepatic metastases from colorectal cancer who are receiving TAS-102 and SBRT to the liver.

OUTLINE: This is a phase Ib, dose-escalation study of trifluridine and tipiracil hydrochloride followed by a phase II study.

Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and 8-12. Patients also undergo SBRT 2-4 times weekly for no more than 2 consecutive days on days 1-12 for a total of 5-6 fractions.

After completion of study treatment, patients are followed up at 1 month and then every 3 months for 2 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Theodore Sunki Hong

  • Primary ID 17-231
  • Secondary IDs NCI-2017-02338
  • Clinicaltrials.gov ID NCT03223779