Trial Outcomes & Findings for TAS-102 in Treating Advanced Biliary Tract Cancers (NCT NCT03278106)

Last Updated: 2023-06-28

Results Overview

16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

16 weeks

Results posted on

2023-06-28

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (TAS-102) Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	28
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (TAS-102) Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study No protocol treatment	1

Baseline Characteristics

TAS-102 in Treating Advanced Biliary Tract Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (TAS-102) n=27 Participants Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	62.3 years STANDARD_DEVIATION 8.3 • n=99 Participants
Sex: Female, Male Female	13 Participants n=99 Participants
Sex: Female, Male Male	14 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	26 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
ECOG Performance Status 0	12 Participants n=99 Participants
ECOG Performance Status 1	15 Participants n=99 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: Primary analysis population

Outcome measures

Outcome measures
Measure	Treatment (TAS-102) n=25 Participants Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
16-Week Progression-free Survival (PFS) Rate	32.0 percentage of patients Interval 14.9 to 53.5

SECONDARY outcome

Timeframe: Up to 3 years

ORR defined as the percentage of patients who experience either a partial response or complete response by the given time point. Complete Response (CR):All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to \<1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD.

Outcome measures

Outcome measures
Measure	Treatment (TAS-102) n=27 Participants Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Response Rate (ORR)	0 percentage of patients Interval 0.0 to 12.8

SECONDARY outcome

Timeframe: Time from study entry to the first of either disease progression or death from any cause, assessed up to 3 years

PFS will be estimated using the Kaplan-Meier method. Progression-Free Survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. Patients will be censored at the last disease assessment date. The median PFS and 95% confidence interval will be reported.

Outcome measures

Outcome measures
Measure	Treatment (TAS-102) n=27 Participants Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS)	3.8 months Interval 2.0 to 5.8

SECONDARY outcome

Timeframe: Time from study entry to death from any cause, assessed up to 3 years

OS will be estimated using the Kaplan-Meier method. OS is defined as the time from study entry to death from any cause. Patients will be censored at the date patient was last known to be alive. The median OS and 95% confidence interval will be reported.

Outcome measures

Outcome measures
Measure	Treatment (TAS-102) n=27 Participants Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS)	6.1 months Interval 4.4 to 11.4

SECONDARY outcome

Timeframe: Up to 3 years

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Outcome measures

Outcome measures
Measure	Treatment (TAS-102) n=27 Participants Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Grade 3	48.1 percentage of patients
Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Grade 4	11.1 percentage of patients

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 3 years

Will correlate with efficacy endpoints.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Will determine if different mutations status of the tumor will affect efficacy endpoints.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (TAS-102)

Serious events: 10 serious events

Other events: 27 other events

Deaths: 21 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (TAS-102) n=27 participants at risk Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	7.4% 2/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Cardiac disorders Sinus tachycardia	3.7% 1/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Abdominal pain	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
General disorders Fever	3.7% 1/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	7.4% 2/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Infections and infestations Biliary tract infection	3.7% 1/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.
Infections and infestations Hepatic infection	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
Infections and infestations Infections and infestations - Other, specify	7.4% 2/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Investigations Blood bilirubin increased	14.8% 4/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	7.4% 2/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Nervous system disorders Cognitive disturbance	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.

Other adverse events

Other adverse events
Measure	Treatment (TAS-102) n=27 participants at risk Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	92.6% 25/27 • Number of events 83 • Up to 3 years All patient adverse events are summarized below.
Eye disorders Watering eyes	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Abdominal pain	81.5% 22/27 • Number of events 66 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Ascites	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Constipation	18.5% 5/27 • Number of events 9 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Diarrhea	44.4% 12/27 • Number of events 36 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Mucositis oral	7.4% 2/27 • Number of events 3 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Nausea	63.0% 17/27 • Number of events 52 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Oral pain	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
Gastrointestinal disorders Vomiting	33.3% 9/27 • Number of events 11 • Up to 3 years All patient adverse events are summarized below.
General disorders Edema limbs	11.1% 3/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.
General disorders Fatigue	100.0% 27/27 • Number of events 93 • Up to 3 years All patient adverse events are summarized below.
General disorders Fever	3.7% 1/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
General disorders General disorders and administration site conditions - Other, specify	18.5% 5/27 • Number of events 7 • Up to 3 years All patient adverse events are summarized below.
General disorders Neck edema	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
Investigations Alanine aminotransferase increased	7.4% 2/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.
Investigations Alkaline phosphatase increased	22.2% 6/27 • Number of events 9 • Up to 3 years All patient adverse events are summarized below.
Investigations Aspartate aminotransferase increased	14.8% 4/27 • Number of events 6 • Up to 3 years All patient adverse events are summarized below.
Investigations Blood bilirubin increased	14.8% 4/27 • Number of events 5 • Up to 3 years All patient adverse events are summarized below.
Investigations Lymphocyte count decreased	11.1% 3/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.
Investigations Neutrophil count decreased	55.6% 15/27 • Number of events 38 • Up to 3 years All patient adverse events are summarized below.
Investigations Platelet count decreased	59.3% 16/27 • Number of events 38 • Up to 3 years All patient adverse events are summarized below.
Investigations White blood cell decreased	44.4% 12/27 • Number of events 20 • Up to 3 years All patient adverse events are summarized below.
Metabolism and nutrition disorders Anorexia	74.1% 20/27 • Number of events 54 • Up to 3 years All patient adverse events are summarized below.
Metabolism and nutrition disorders Hypoalbuminemia	3.7% 1/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 2/27 • Number of events 9 • Up to 3 years All patient adverse events are summarized below.
Musculoskeletal and connective tissue disorders Back pain	14.8% 4/27 • Number of events 6 • Up to 3 years All patient adverse events are summarized below.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.4% 2/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 1/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	3.7% 1/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Nervous system disorders Headache	3.7% 1/27 • Number of events 8 • Up to 3 years All patient adverse events are summarized below.
Nervous system disorders Peripheral sensory neuropathy	11.1% 3/27 • Number of events 6 • Up to 3 years All patient adverse events are summarized below.
Psychiatric disorders Confusion	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
Psychiatric disorders Insomnia	3.7% 1/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.4% 2/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.
Skin and subcutaneous tissue disorders Alopecia	7.4% 2/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Skin and subcutaneous tissue disorders Pruritus	3.7% 1/27 • Number of events 1 • Up to 3 years All patient adverse events are summarized below.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	3.7% 1/27 • Number of events 2 • Up to 3 years All patient adverse events are summarized below.
Vascular disorders Hypertension	7.4% 2/27 • Number of events 4 • Up to 3 years All patient adverse events are summarized below.

Additional Information

Amit Mahipal MBBS

Mayo Clinic

Phone: +1 (507) 293-0487

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place