Advanced Bile Duct CarcinomaPhase 2NCT04072445
Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer
A Phase 2 study testing Irinotecan, Irinotecan Hydrochloride and Trifluridine and Tipiracil Hydrochloride in people with Advanced Bile Duct Carcinoma and Advanced Gallbladder Carcinoma, run by Mayo Clinic at 1 site in United States.
Trial summary
This phase II trial studies how well trifluridine/tipiracil and irinotecan work in treating patients with biliary tract cancer that has spread to other places in the body (advanced) and has not responded to treatment (refractory). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Bile Duct Carcinoma, Advanced Gallbladder Carcinoma, Refractory Bile Duct Carcinoma
- What is being tested?
- Irinotecan, Irinotecan Hydrochloride and Trifluridine and Tipiracil Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Oct 2019to 13 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histological confirmation of advanced biliary tract cancers including cancers originating in the gallbladder who have received at least one line of systemic anticancer therapy
- Note: Patients who have either progressed on or are intolerant to the prior therapy can be included in this study
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease. Disease that is measurable by physical examination only is not eligible
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Absolute neutrophil count (ANC) >= 1500/mm^3 (=< 21 days prior to registration)
Show all 14Show fewer
- Platelet count >= 100,000/mm^3 (=< 21 days prior to registration)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (=< 21 days prior to registration)
- Aspartate transaminase (AST) or alanine transaminase (ALT) =< 3 x ULN (=< 21 days prior to registration)
- Creatinine =< 1.5 x ULN (=< 21 days prior to registration)
- Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
- Provide written informed consent
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Willingness to provide mandatory blood and tissue specimens for correlative research
Who cannot join
- Any of the following because this study involves an agent that has potential genotoxic, mutagenic and teratogenic effects:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential who are unwilling to employ adequate contraception for at least 3 months after the last dose of the study drug
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
Show all 15Show fewer
- NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 21 days prior to registration
- Receiving any anticancer therapy for biliary tract cancer =< 21 days prior to registration
- Other active malignancy requiring treatment in =< 6 months prior to registration
- EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
- NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
- History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- Previous treatment with irinotecan or irinotecan-based chemotherapy for biliary tract cancers
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Trifluridine/Tipiracil in Combination With Irinotecan in Biliary Tract Cancers
This phase II trial studies how well trifluridine/tipiracil and irinotecan work in treating patients with biliary tract cancer that has spread to other places in the body (advanced) and has not responded to treatment (refractory). Trifluridine/tipiracil and irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the efficacy of trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) in combination with irinotecan hydrochloride (irinotecan) in patients with refractory biliary tract cancers using progression-free survival (PFS) at 16 weeks.
SECONDARY OBJECTIVES:
- Assess the safety and tolerability of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers through adverse event monitoring.
II. Further explore the efficacy of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers by overall response rates (ORR), disease control rates (DCR), and overall survival (OS).
CORRELATIVE RESEARCH:
- To determine if the number of circulating tumor cells (CTCs) or the level of cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline is prognostic or predictive to the response to therapy.
II. To determine if changes in CTCs or cfDNA correlate with efficacy endpoints. III. To determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine/tipiracil plus irinotecan.
IV. To evaluate the role of thymidine kinase 1 (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.
EXPLORATORY RESEARCH:
- To evaluate patients who received prior treatment with fluorouracil (5-FU) independently from the entire population in the following areas: PFS, safety and tolerability, ORR, DCR, and OS.
OUTLINE:
Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (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.
After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 2 years after study registration.
- Conditions
- Advanced Bile Duct Carcinoma, Advanced Gallbladder Carcinoma, Refractory Bile Duct Carcinoma, Refractory Gallbladder Carcinoma, Stage III Distal Bile Duct Cancer AJCC v8, Stage III Gallbladder Cancer AJCC v8
- Being tested
- Irinotecan, Irinotecan Hydrochloride, Trifluridine and Tipiracil Hydrochloride
- Medical subject headings
- Bile Duct Neoplasms, Gallbladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrinotecanDrug
Given IV
Also called Campto, Camptosar, Camptothecin 11, Camptothecin-11
Given IV
Trifluridine and Tipiracil HydrochlorideDrug
Also called Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (trifluridine and tipiracil, irinotecan) | Experimental | 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. Receives: Drug: Irinotecan; Drug: Irinotecan Hydrochloride; Drug: Trifluridine and Tipiracil Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
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.
Measured: Up to 16 weeks
Secondary outcomes (5)
Overall Response Rate (ORR)
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.
Measured: Up to 20 months
Disease Control Rate (DCR)
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.
Measured: Up to 20 months
PFS
Will 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.
Measured: From study entry to the first of either disease progression or death from any cause, assessed up to 20 months
Overall Survival (OS)
Will 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.
Measured: From study entry to death from any cause, assessed up to 20 months
Number of Participants With Adverse Events
The 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.
Measured: Up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start18 Oct 2019
- Primary completion13 Aug 2021
- Study completion13 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Bile Duct CarcinomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Amit Mahipal, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04072445
- Sponsor's protocol ID
- MC1941
- Other IDs
- NCI-2019-05653, MC1941
- Status last verified
- Jul 2023
- First submitted
- 27 Aug 2019
- Last updated
- 9 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Tella SH, Foster N, Qian S, Nguyen T, Borad MJ, McWilliams RR, Alberts SR, Wee Ma W, Chakrabarti S, Fruth B, Wessling J, Hartgers M, Washburn L, Fernandez-Zapico ME, Hogenson TL, Pitot H, Jin Z, Mahipal A. Phase II Trial of Trifluridine/Tipiracil Plus Irinotecan in Patients with Advanced, Refractory Biliary Tract Carcinoma. Oncologist. 2023 Oct 3;28(10):917-e966. doi: 10.1093/oncolo/oyad144.
PubMed 37339254
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Trifluridine/Tipiracil in Combination With Irinotecan in Biliary Tract Cancers
- ClinicalTrials.gov ID
- NCT04072445
- Acronym / sponsor ID
- MC1941
- Conditions
- Advanced Bile Duct Carcinoma, Advanced Gallbladder Carcinoma, Refractory Bile Duct Carcinoma, Refractory Gallbladder Carcinoma, Stage III Distal Bile Duct Cancer AJCC v8, Stage III Gallbladder Cancer AJCC v8
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network
- Study start
- 18 Oct 2019 (actual)
- Primary completion
- 13 Aug 2021 (actual)
- Study completion
- 13 Aug 2021 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Posted 22 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well trifluridine/tipiracil and irinotecan work in treating patients with biliary tract cancer that has spread to other places in the body (advanced) and has not responded to treatment (refractory). Trifluridine/tipiracil and irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVE:
- Determine the efficacy of trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) in combination with irinotecan hydrochloride (irinotecan) in patients with refractory biliary tract cancers using progression-free survival (PFS) at 16 weeks.
SECONDARY OBJECTIVES:
- Assess the safety and tolerability of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers through adverse event monitoring.
II. Further explore the efficacy of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers by overall response rates (ORR), disease control rates (DCR), and overall survival (OS).
CORRELATIVE RESEARCH:
- To determine if the number of circulating tumor cells (CTCs) or the level of cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline is prognostic or predictive to the response to therapy.
II. To determine if changes in CTCs or cfDNA correlate with efficacy endpoints. III. To determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine/tipiracil plus irinotecan.
IV. To evaluate the role of thymidine kinase 1 (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.
EXPLORATORY RESEARCH:
- To evaluate patients who received prior treatment with fluorouracil (5-FU) independently from the entire population in the following areas: PFS, safety and tolerability, ORR, DCR, and OS.
OUTLINE:
Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (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.
After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 2 years after study registration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (trifluridine and tipiracil, irinotecan) | Experimental | Drug: Irinotecan, Drug: Irinotecan Hydrochloride, Drug: Trifluridine and Tipiracil HydrochloridePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histological confirmation of advanced biliary tract cancers including cancers originating in the gallbladder who have received at least one line of systemic anticancer therapy
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Absolute neutrophil count (ANC) >= 1500/mm^3 (=< 21 days prior to registration)
- Platelet count >= 100,000/mm^3 (=< 21 days prior to registration)
Key exclusion criteria (15 listed)
- Any of the following because this study involves an agent that has potential genotoxic, mutagenic and teratogenic effects:
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 21 days prior to registration
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 |
|---|---|---|
| IrinotecanGiven IV | Drug | Treatment (trifluridine and tipiracil, irinotecan) |
| Irinotecan HydrochlorideAlso: Campto, Camptosar, Camptothecin 11, Camptothecin-11Given IV | Drug | Treatment (trifluridine and tipiracil, irinotecan) |
| Trifluridine and Tipiracil HydrochlorideAlso: Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with TrifluridineGiven PO | Drug | Treatment (trifluridine and tipiracil, irinotecan) |
Primary outcome
Progression-free Survival (PFS)
Time frame: Up to 16 weeks
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.
5 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to 20 months
Disease Control Rate (DCR)
Time frame: Up to 20 months
PFS
Time frame: From study entry to the first of either disease progression or death from any cause, assessed up to 20 months
Overall Survival (OS)
Time frame: From study entry to death from any cause, assessed up to 20 months
Number of Participants With Adverse Events
Time frame: Up to 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37339254Tella SH, Foster N, Qian S, Nguyen T, Borad MJ, McWilliams RR, Alberts SR, Wee Ma W, Chakrabarti S, Fruth B, Wessling J, Hartgers M, Washburn L, Fernandez-Zapico ME, Hogenson TL, Pitot H, Jin Z, Mahipal A. Phase II Trial of Trifluridine/Tipiracil Plus Irinotecan in Patients with Advanced, Refractory Biliary Tract Carcinoma. Oncologist. 2023 Oct 3;28(10):917-e966. doi: 10.1093/oncolo/oyad144.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
Related trials for Advanced Bile Duct Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 2
Gemcitabine, Cisplatin, Nab-paclitaxel (GAP) and Cemiplimab for Locally Advanced Biliary Tract Cancer (BTC)
Colon and Rectal Cancer
RecruitingPhase 2
MP0317 in Combination With Chemoimmunotherapy in First Line Treatment for Patients With Advanced Biliary Tract Carcinoma
Advanced Biliary Tract Carcinoma
RecruitingPhase 3
D07001 Softgel-Capsules and Capecitabine Combination Therapy in Patients With Advanced Biliary Tract Cancer
Biliary Tract Cancer (BTC)
Not yet recruitingPhase 2
Daraxonrasib in Asian RAS-mutant Biliary Tract Cancer
Biliary Tract Cancer (BTC)
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.
Amit Mahipal principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Irinotecan, Irinotecan Hydrochloride and Trifluridine and Tipiracil Hydrochloride in people with Advanced Bile Duct Carcinoma and Advanced Gallbladder Carcinoma, run by Mayo Clinic 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 14 inclusion and 15 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 9 Aug 2023. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 22 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival (PFS) (time frame: Up to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04072445, which also lists 1 linked publication.
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 9 Aug 2023.