Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT03223779|
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : July 19, 2018
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
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Drug: TAS-102 Radiation: Photon SBRT||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||56 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 13, 2017|
|Estimated Primary Completion Date :||January 31, 2021|
|Estimated Study Completion Date :||January 31, 2025|
Trifluridine stops DNA replication which may prevent the cancer cells from growing
Radiation: Photon SBRT
SBRT stands for Stereotactic Body Radiation Therapy. Radiation may help to kill the cancer cells while protecting your normal tissue cells
- 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.
- Toxicity associated with TAS-102 combined with SBRT [ Time Frame: From start of treatment until 4 weeks after the end of treatment ]Summary of the Adverse events experienced during treatment. Adverse events are assessed with Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
- Progression Free Survival [ Time Frame: from the start of treatment until 2 years, or until time of progression/death ]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.
- Overall Survival [ Time Frame: from the start of treatment until 2 years, or until time of death ]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.
- 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 ]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.
- Serial ctDNA [ Time Frame: Baseline, week 1, week 2, 1 month post treatment, at the time of progression ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03223779
|Contact: Theodore S Hong, MDfirstname.lastname@example.org|
|Contact: Tarin Grilloemail@example.com|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Theodore S. Hong, MD 617-724-8770 firstname.lastname@example.org|
|Principal Investigator: Theodore S. Hong, MD|
|Principal Investigator:||Theodore S. Hong, MD||Massachusetts General Hospital|