Colorectal CancerPhase 1/2NCT03223779
Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer
A Phase 1/2 study testing TAS-102 and Photon SBRT in people with Colorectal Cancer, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research study is studying a drug in combination with radiation therapy as a possible treatment for hepatic metastases from colorectal cancer. The interventions involved in this study are: Trifluridine (TAS-102) Radiation Therapy Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- TAS-102 and Photon SBRT
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2017to 2 Oct 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 CT scan. See Section 13 for the evaluation of measurable disease.
- 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.
- Participants must be 18 years of age or older.
- Because no dosing or adverse event data are currently available on the use of high dose liver radiation in participants <18 years of age, children are excluded from this study.
- Expected survival must be greater than three months.
Show all 19Show fewer
- ECOG Performance Status 0 or 1..
- Participants must have liver metastases deemed unresectable due to anatomy, medical fitness, or presence of extrahepatic disease.
- Participants must have normal organ and marrow function as defined below. History of transfusion is acceptable and transfusions may be given to meet eligibility requirements.
- Hgb ≥ 9g/dL
- Absolute neutrophil count ≥ 1,500/mm3
- Platelets ≥ 75,000/mm3
- Total bilirubin ≤ 1.5 X institutional upper limit of normal
- AST (SGOT) and ALT (SGPT) ≤ 1.5 X institutional upper limit of normal
- Creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 mL/min/1.73 m2 (Calculated per Cockroft \& 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 PT/INR are required for Child-Pugh classification; these labs should be drawn with other labs required for eligibility analysis. See Appendix B for Child-Pugh classification table.
- The effects of radiation on the developing human fetus are known to be teratogenic and the safety of TAS-102 in pregnant women and their fetuses has not been established. Therefore, 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)
Who cannot join
- 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. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiation, breastfeeding should be discontinued if the mother is treated with radiation.
- Participants with gross ascites or encephalopathy
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02215
About this study
Official title: Phase Ib/II Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer
This research study is studying a drug in combination with radiation therapy as a possible treatment for hepatic metastases from colorectal cancer.
The interventions involved in this study are:
- Trifluridine (TAS-102)
- Radiation Therapy
Read the detailed description
This is a Phase I/II clinical trial. Patients are being asked to participate in the Phase I portion of the study. A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has approved Trifluridine as a treatment option for this disease.
The FDA has not approved Trifluridine in combination with radiation therapy as a treatment option for this disease.
In this research study, the investigators are determining the safest and most effective dose of Trifluridine in combination with radiation therapy in participants with hepatic metastases from colorectal cancer.
Trifluridine stops DNA replication which may prevent the cancer cells from growing. Radiation may help to kill the cancer cells while protecting normal tissue cells. Studies have shown Trifluridine may make radiation more effective.
- Conditions
- Colorectal Cancer
- Being tested
- TAS-102, Photon SBRT
- Keywords
- Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAS-102Drug
Also called Lonsurf, Trifluridine
Trifluridine stops DNA replication which may prevent the cancer cells from growing
Photon SBRTRadiation
SBRT stands for Stereotactic Body Radiation Therapy. Radiation may help to kill the cancer cells while protecting your normal tissue cells
| Study group | Role | What they receive |
|---|---|---|
| TAS-102 | Experimental | * Photon treatments will be performed on a linear accelerator
* Photon SBRT will be given during TAS-102 dosing
* TAS-102 dosing occurs on days 1 through 5 and 8 through 12
* TAS-102 tablets should be taken twice a day orally Receives: Drug: TAS-102; Radiation: Photon SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
MTD will be determined using a 3 + 3 dose escalation. 3 participants enrolled at the starting dose of 20 mg/m2 BID (Bis in die, Latin for twice daily). Based on the number of dose limiting toxicities (DLT), the dose can be either be increased to 25 mg/m2 BID then 30 mg/m2 BID or it could be reduced to 15 mg/m2 BID.
- If 0 out of 3 have DLT, enroll 3 participants at next dose level
- If ≥ 2 DLT out of 3 or 6 participants in a dose cohort have DLT, this will be the MTD and 3 additional participants are enrolled at next lowest dose if only 3 were treated at that level so far.
- If 1 out of 3 have DLT, 3 more enrolled at current dose level. If no DLT in those 3, move to next dose level. If ≥ 1 DLT, declare this the MTD and enroll 3 additional at next lowest dose if only 3 treated so far.
- If ≤ 1 out of 6 DLT at highest dose level below maximally administered dose, MTD is generally the rerecorded phase 2 dose (RP2D). Dose level 3 is RP2D if MTD not reached.
Measured: From start of treatment until 4 weeks after the end of treatment
The Duration of Local Control
Local control is the absence of local failure defined as evidence of tumor growth/regrowth that meets Response Evaluation Criteria In Solid Tumors (RECIST) criteria for progressive disease in any direction beyond that present in pre-treatment imaging studies of the treated lesion(s). The duration of local control will be measured from the start date of protocol treatment until the date of local failure.
- Marginal failure is defined as appearance of tumor growth at the margin of the target volume.
- Nodal failure is defined as failure in regional lymph nodes (i.e. porta-hepatis, para-aortic, diaphragmatic).
- Distant failure is defined as appearance of tumor at sites beyond marginal and regional nodal sites.
- Intrahepatic recurrence is defined as any new lesion elsewhere in the liver and separate from local failure.
Measured: Baseline, 1 month post treatment, every 6 months for two years or until death
Secondary outcomes (5)
Toxicity associated with TAS-102 combined with SBRT
Summary of the Adverse events experienced during treatment. Adverse events are assessed with Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Measured: From start of treatment until 4 weeks after the end of treatment
Progression Free Survival
Progression-free survival (PFS) will be measured from the start date of protocol treatment (first TAS-102 dose and/or first SBRT fraction) to the earlier date of first failure at any pre-treatment or new site (defined in 'Duration of Local Control' section) or death. PFS will be censored at the date of last follow-up for participants still alive who have not failed.
Measured: from the start of treatment until 2 years, or until time of progression/death
Overall Survival
Overall survival (OS) will be measured from the start date of protocol treatment (first TAS-102 dose and/or first SBRT fraction) to the date of death. OS will be censored at the date of last follow-up for participants who are still alive.
Measured: from the start of treatment until 2 years, or until time of death
Association between KRAS or BRAF mutation status with local control
Association between KRAS or BRAF mutation status with local control will be assessed using Gray's test with death as a competing risk in the absence of local failure. Local control is defined in the 'Duration of Local Control' description.
Measured: Baseline, 1 month post treatment, every 6 months for two years or until death
Serial ctDNA
Serial ctDNA will be analyzed by descriptive methods to identify potential trends and correlations with synchronous radiologic endpoints (baseline, one month post-treatment). ctDNA level (detectable versus negative) at early (week 1, week 2) and post-treatment (one month) assessments will be analyzed for differences in local control
Measured: Baseline, week 1, week 2, 1 month post treatment, at the time of progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start13 Oct 2017
- Primary completion3 Feb 2025
- Study completion2 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Taiho Oncology, Inc.
- Responsible party
- Principal investigator, Jennifer Wo, Massachusetts General Hospital
- Investigators
- Jennifer Y. Wo, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03223779
- Sponsor's protocol ID
- 17-231
- Status last verified
- Mar 2026
- First submitted
- 12 Jul 2017
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03223779
- Acronym / sponsor ID
- 17-231
- Conditions
- Colorectal Cancer
- Keywords
- Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Taiho Oncology, Inc.
- Study start
- 13 Oct 2017 (actual)
- Primary completion
- 3 Feb 2025 (actual)
- Study completion
- 2 Oct 2025 (actual)
- First posted
- 21 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a drug in combination with radiation therapy as a possible treatment for hepatic metastases from colorectal cancer.
The interventions involved in this study are:
- Trifluridine (TAS-102)
- Radiation Therapy
Detailed description
This is a Phase I/II clinical trial. Patients are being asked to participate in the Phase I portion of the study. A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has approved Trifluridine as a treatment option for this disease.
The FDA has not approved Trifluridine in combination with radiation therapy as a treatment option for this disease.
In this research study, the investigators are determining the safest and most effective dose of Trifluridine in combination with radiation therapy in participants with hepatic metastases from colorectal cancer.
Trifluridine stops DNA replication which may prevent the cancer cells from growing. Radiation may help to kill the cancer cells while protecting normal tissue cells. Studies have shown Trifluridine may make radiation more effective.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TAS-102 | Experimental | Drug: TAS-102, Radiation: Photon SBRT* Photon treatments will be performed on a linear accelerator * Photon SBRT will be given during TAS-102 dosing * TAS-102 dosing occurs on days 1 through 5 and 8 through 12 * TAS-102 tablets should be taken twice a day orally |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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 CT scan. See Section 13 for the evaluation of measurable disease.
- 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.
- Participants must be 18 years of age or older.
- Because no dosing or adverse event data are currently available on the use of high dose liver radiation in participants <18 years of age, children are excluded from this study.
Key exclusion criteria (9 listed)
- 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. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiation, breastfeeding should be discontinued if the mother is treated with radiation.
- Participants with gross ascites or encephalopathy
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAS-102Also: Lonsurf, TrifluridineTrifluridine stops DNA replication which may prevent the cancer cells from growing | Drug | TAS-102 |
| Photon SBRTSBRT stands for Stereotactic Body Radiation Therapy. Radiation may help to kill the cancer cells while protecting your normal tissue cells | Radiation | TAS-102 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: From start of treatment until 4 weeks after the end of treatment
MTD will be determined using a 3 + 3 dose escalation. 3 participants enrolled at the starting dose of 20 mg/m2 BID (Bis in die, Latin for twice daily). Based on the number of dose limiting toxicities (DLT), the dose can be either be increased to 25 mg/m2 BID then 30 mg/m2 BID or it could be reduced to 15 mg/m2 BID. * If 0 out of 3 have DLT, enroll 3 participants at next dose level * If ≥ 2 DLT out of 3 or 6 participants in a dose cohort have DLT, this will be the MTD and 3 additional participants are enrolled at next lowest dose if only 3 were treated at that level so far. * If 1 out of 3 have DLT, 3 more enrolled at current dose level. If no DLT in those 3, move to next dose level. If ≥ 1 DLT, declare this the MTD and enroll 3 additional at next lowest dose if only 3 treated so far. * If ≤ 1 out of 6 DLT at highest dose level below maximally administered dose, MTD is generally the rerecorded phase 2 dose (RP2D). Dose level 3 is RP2D if MTD not reached.
The Duration of Local Control
Time frame: Baseline, 1 month post treatment, every 6 months for two years or until death
Local control is the absence of local failure defined as evidence of tumor growth/regrowth that meets Response Evaluation Criteria In Solid Tumors (RECIST) criteria for progressive disease in any direction beyond that present in pre-treatment imaging studies of the treated lesion(s). The duration of local control will be measured from the start date of protocol treatment until the date of local failure. * Marginal failure is defined as appearance of tumor growth at the margin of the target volume. * Nodal failure is defined as failure in regional lymph nodes (i.e. porta-hepatis, para-aortic, diaphragmatic). * Distant failure is defined as appearance of tumor at sites beyond marginal and regional nodal sites. * Intrahepatic recurrence is defined as any new lesion elsewhere in the liver and separate from local failure.
5 secondary outcomes
Toxicity associated with TAS-102 combined with SBRT
Time frame: From start of treatment until 4 weeks after the end of treatment
Progression Free Survival
Time frame: from the start of treatment until 2 years, or until time of progression/death
Overall Survival
Time frame: from the start of treatment until 2 years, or until time of death
Association between KRAS or BRAF mutation status with local control
Time frame: Baseline, 1 month post treatment, every 6 months for two years or until death
Serial ctDNA
Time frame: Baseline, week 1, week 2, 1 month post treatment, at the time of progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Y. Wo, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TAS-102 and Photon SBRT in people with Colorectal Cancer, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: From start of treatment until 4 weeks after the end of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2026.