Trial Outcomes & Findings for Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer (NCT NCT04072445)
NCT ID: NCT04072445
Last Updated: 2023-08-09
Results Overview
Will be defined as the proportion of evaluable patients who are progression-free (stable disease, partial response, complete response) at 16 weeks and assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.
COMPLETED
PHASE2
28 participants
Up to 16 weeks
2023-08-09
Participant Flow
Participant milestones
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.\>
\> Irinotecan: Given IV\>
\> Irinotecan Hydrochloride: Given IV\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Overall Study
STARTED
|
28
|
|
Overall Study
COMPLETED
|
27
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=28 Participants
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.\>
\> Irinotecan: Given IV\>
\> Irinotecan Hydrochloride: Given IV\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Age, Continuous
|
64.8 years
STANDARD_DEVIATION 9.49 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Prior treatment
1
|
10 Participants
n=5 Participants
|
|
Prior treatment
2
|
11 Participants
n=5 Participants
|
|
Prior treatment
3+
|
7 Participants
n=5 Participants
|
|
Primary Site of Tumor
Extrahepatic biliary tract cancer
|
9 Participants
n=5 Participants
|
|
Primary Site of Tumor
Gallbladder
|
3 Participants
n=5 Participants
|
|
Primary Site of Tumor
Intrahepatic
|
16 Participants
n=5 Participants
|
|
Degree of differentiation
Moderately
|
18 Participants
n=5 Participants
|
|
Degree of differentiation
Poorly differentiated
|
10 Participants
n=5 Participants
|
|
ECOG Performance Status (PS)
0
|
4 Participants
n=5 Participants
|
|
ECOG Performance Status (PS)
1
|
24 Participants
n=5 Participants
|
|
Prior treatment with fluoropyrimidine based regimen
Yes
|
3 Participants
n=5 Participants
|
|
Prior treatment with fluoropyrimidine based regimen
No
|
25 Participants
n=5 Participants
|
|
Metastatic Sites
Bone
|
1 Participants
n=5 Participants
|
|
Metastatic Sites
Liver
|
25 Participants
n=5 Participants
|
|
Metastatic Sites
Peritoneum
|
3 Participants
n=5 Participants
|
|
Metastatic Sites
Lung
|
4 Participants
n=5 Participants
|
|
Metastatic Sites
Nodal
|
3 Participants
n=5 Participants
|
|
Metastatic Sites
Abdominal Wall
|
1 Participants
n=5 Participants
|
|
Metastatic Sites
Interaortocaval LN
|
2 Participants
n=5 Participants
|
|
Metastatic Sites
Pancreas
|
1 Participants
n=5 Participants
|
|
Metastatic Sites
Perisplenic and Perihepatic
|
1 Participants
n=5 Participants
|
|
Metastatic Sites
Soft tissue, adrenal gland.
|
1 Participants
n=5 Participants
|
|
Metastatic Sites
abdominal wall, mesenteric node.
|
1 Participants
n=5 Participants
|
|
Metastatic Sites
hepatic duct
|
1 Participants
n=5 Participants
|
|
MedDRA disease code
Cholangiocarcinoma, intrahepatic and extrahepatic bile ducts (adenocarcinoma)
|
24 Participants
n=5 Participants
|
|
MedDRA disease code
Gall Bladder Carcinoma
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 16 weeksWill be defined as the proportion of evaluable patients who are progression-free (stable disease, partial response, complete response) at 16 weeks and assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.
Outcome measures
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=27 Participants
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
\>
\> Irinotecan: Given IV
\>
\> Irinotecan Hydrochloride: Given IV
\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Progression-free Survival (PFS)
|
37.0 percentage of participants
Interval 19.4 to 57.6
|
SECONDARY outcome
Timeframe: Up to 20 monthsPopulation: 7 patients went off treatment early on and weren't evaluated for response post-baseline
Will be defined as the proportion of patients who experience either a partial response or complete response as their best response. ORR will be reported descriptively and a 95% confidence interval will be reported.
Outcome measures
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=20 Participants
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
\>
\> Irinotecan: Given IV
\>
\> Irinotecan Hydrochloride: Given IV
\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Overall Response Rate (ORR)
|
20.0 percentage of participants
Interval 5.7 to 43.7
|
SECONDARY outcome
Timeframe: Up to 20 monthsPopulation: 7 patients went off treatment early on and weren't evaluated for response post-baseline
Will be defined as the proportion of patients who experience a partial response, complete response, or have stable disease as their best response. DCR will be reported descriptively and a 95% confidence interval will be reported.
Outcome measures
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=20 Participants
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
\>
\> Irinotecan: Given IV
\>
\> Irinotecan Hydrochloride: Given IV
\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Disease Control Rate (DCR)
|
50 percentage of participants
Interval 27.2 to 72.8
|
SECONDARY outcome
Timeframe: From study entry to the first of either disease progression or death from any cause, assessed up to 20 monthsWill be determined based on RECIST v 1.1. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported. Patients will be censored at the last disease assessment date.
Outcome measures
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=27 Participants
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
\>
\> Irinotecan: Given IV
\>
\> Irinotecan Hydrochloride: Given IV
\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
PFS
|
3.9 months
Interval 2.5 to 7.4
|
SECONDARY outcome
Timeframe: From study entry to death from any cause, assessed up to 20 monthsWill be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported. Patients will be censored at the date patient was last known to be alive.
Outcome measures
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=27 Participants
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
\>
\> Irinotecan: Given IV
\>
\> Irinotecan Hydrochloride: Given IV
\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Overall Survival (OS)
|
9.1 months
Interval 8.0 to 14.3
|
SECONDARY outcome
Timeframe: Up to 28 daysThe maximum grade for each type of adverse event by patient will be summarized by frequencies and percentages using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Outcome measures
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=27 Participants
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
\>
\> Irinotecan: Given IV
\>
\> Irinotecan Hydrochloride: Given IV
\>
\> Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Number of Participants With Adverse Events
Grade 3+ AE
|
20 Participants
|
|
Number of Participants With Adverse Events
Grade 4 AE
|
4 Participants
|
|
Number of Participants With Adverse Events
Grade 5 AE
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselineWill 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: Baseline up to 20 monthsWill determine if change in CTCs or cfDNA will correlate with efficacy endpoints.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 20 monthsWill determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) plus irinotecan hydrochloride (irinotecan).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselineWill evaluate the role of TK1 in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Trifluridine and Tipiracil, Irinotecan)
Serious adverse events
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=27 participants at risk
Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Gastrointestinal disorders
Abdominal pain
|
3.7%
1/27 • Number of events 2 • 20 months
|
|
Gastrointestinal disorders
Ascites
|
7.4%
2/27 • Number of events 2 • 20 months
|
|
Gastrointestinal disorders
Diarrhea
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
General disorders
Non-cardiac chest pain
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Infections and infestations
Biliary tract infection
|
11.1%
3/27 • Number of events 3 • 20 months
|
|
Infections and infestations
Infections and infestations - Oth spec
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Infections and infestations
Sepsis
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Injury, poisoning and procedural complications
Intraoperative hemorrhage
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.7%
1/27 • Number of events 1 • 20 months
|
Other adverse events
| Measure |
Treatment (Trifluridine and Tipiracil, Irinotecan)
n=27 participants at risk
Trifluridine and Tipiracil Hydrochloride: Given PO
|
|---|---|
|
Investigations
Lymphocyte count decreased
|
51.9%
14/27 • Number of events 59 • 20 months
|
|
Investigations
Neutrophil count decreased
|
66.7%
18/27 • Number of events 34 • 20 months
|
|
Investigations
Platelet count decreased
|
63.0%
17/27 • Number of events 90 • 20 months
|
|
Investigations
White blood cell decreased
|
48.1%
13/27 • Number of events 29 • 20 months
|
|
Metabolism and nutrition disorders
Anorexia
|
3.7%
1/27 • Number of events 2 • 20 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
3.7%
1/27 • Number of events 5 • 20 months
|
|
Nervous system disorders
Dysgeusia
|
11.1%
3/27 • Number of events 3 • 20 months
|
|
Nervous system disorders
Paresthesia
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.4%
2/27 • Number of events 6 • 20 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.4%
2/27 • Number of events 2 • 20 months
|
|
Vascular disorders
Hypertension
|
14.8%
4/27 • Number of events 8 • 20 months
|
|
Blood and lymphatic system disorders
Anemia
|
96.3%
26/27 • Number of events 208 • 20 months
|
|
Gastrointestinal disorders
Ascites
|
7.4%
2/27 • Number of events 6 • 20 months
|
|
Gastrointestinal disorders
Diarrhea
|
22.2%
6/27 • Number of events 9 • 20 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
3.7%
1/27 • Number of events 2 • 20 months
|
|
Gastrointestinal disorders
Mucositis oral
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Gastrointestinal disorders
Nausea
|
14.8%
4/27 • Number of events 5 • 20 months
|
|
General disorders
Edema limbs
|
7.4%
2/27 • Number of events 2 • 20 months
|
|
General disorders
Fatigue
|
33.3%
9/27 • Number of events 19 • 20 months
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Investigations
Alanine aminotransferase increased
|
3.7%
1/27 • Number of events 1 • 20 months
|
|
Investigations
Alkaline phosphatase increased
|
14.8%
4/27 • Number of events 20 • 20 months
|
|
Investigations
Aspartate aminotransferase increased
|
3.7%
1/27 • Number of events 2 • 20 months
|
|
Investigations
Blood bilirubin increased
|
7.4%
2/27 • Number of events 5 • 20 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place