High-grade Extra Pulmonary Neuroendocrine CancerPhase 2TAS-102 NECNCT04042714
TAS-102 in Extrapulmonary Neuroendocrine Carcinoma
A Phase 2 study testing All patients- TAS-102 in people with High-grade Extra Pulmonary Neuroendocrine Cancer, run by Baylor Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and efficacy of drug, TAS-102 (trifluridine/tipiracil), in patients with extrapulmonary (outside the lung) high-grade neuroendocrine cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High-grade Extra Pulmonary Neuroendocrine Cancer
- What is being tested?
- All patients- TAS-102
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2019to 15 Oct 2025
- Phase
- Phase 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
- Pathologic confirmation of high grade NEC using WHO criteria as determined by Ki67>20%, poorly differentiated (G3) characteristics, or >20 mitotic figures/10 high-power fields.
- Unknown primary may be included. Suspected extrapulmonary patients with known lung primary will be excluded.
- Prior treatment with a platinum containing regimen
- RECIST 1.1 measurable disease
- Evidence of stage IV, metastatic disease
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
Show all 12Show fewer
- Serum albumin ≥2.5 gm/dL.
- Expected survival ≥3 months.
- Adequate hematologic function as defined by: a) Absolute neutrophil count (ANC) >1500/mm3; b) Platelets ≥75,000/mm3; c) Hemoglobin >8 g/dL (in the absence of red blood transfusion).
- Adequate liver function, as defined by: a) Serum total bilirubin ≤2.5 x ULN mg/dL. b) ALT (SGPT) and AST (SGOT) ≤5 x upper limit of normal (ULN).
- Adequate renal function, as defined by serum creatinine ≤2.0 x ULN, or creatinine clearance ≥30 mL/min
- Females of child bearing potential must agree to use contraception to avoid pregnancy throughout the study.
Who cannot join
- Women who are pregnant or breastfeeding.
- Evidence of low-grade or well-differentiated features as determined by the investigator.
- Functional neuroendocrine tumors are excluded.
- Known pulmonary primary or small cell lung cancer will be excluded.
- Significant or uncontrolled congestive heart failure (CHF), myocardial infarction or significant ventricular arrhythmias within the last six months.
- Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38°C).
Show all 9Show fewer
- Other severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as: a) Severe impaired lung functions as defined by spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air, b) Uncontrolled diabetes,c) Liver disease such as cirrhosis or severe hepatic impairment, d) Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the integrity of the study.
- Taking other investigational or anti-cancer treatments while participating in this study. Concurrent radiotherapy is allowed provided to non-target lesions. If target lesions have received radiation therapy, progression must have been demonstrated prior to enrollment.
- Prior or concurrent malignancy, except for the following: a) Adequately treated basal cell or squamous cell skin cancer; b) Cervical carcinoma in situ; c) Adequately treated Stage I or II cancer from which the subject is currently in complete remission; d) Or any other cancer from which the subject has been disease-free for 3 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
Baylor Scott and White University Medical Center,
Dallas, Texas, 75246
About this study
Official title: An Open-label, Phase II Investigation of TAS-102 in Patients With High Grade, Extrapulmonary Neuroendocrine Carcinoma
The purpose of this study is to test the safety and efficacy of drug, TAS-102 (trifluridine/tipiracil), in patients with extrapulmonary (outside the lung) high-grade neuroendocrine cancer. TAS-102 demonstrated improved survival and tolerability in patients with colorectal cancer and is currently approved by the FDA and marketed under the brand name Lonsurf for the treatment of patients with metastatic colorectal cancer (mCRC). Recently, a study evaluating TAS-102 showed a case of complete remission of high-grade NEC. Given the safety profile of TAS-102 and the remarkable single agent activity in a disease with otherwise dismal outcomes, we hope that TAS-102 may show tolerability and efficacy in neuro-endocrine cancer and propose further exploration in patients with extrapulmonary (outside the lung) high-grade neuroendocrine cancer.
Read the detailed description
Neuroendocrine tumors are highly prevalent cancer showing heterogeneous array of behaviors. For intermediate/high grade and poorly differentiated neuroendocrine carcinomas (NEC) that occur outside the lung, there is no acceptable standard of care. Most patients are treated with a platinum-based chemotherapy in the front-line setting and evidence for therapies in the second line setting is minimal representing a significant unmet need. However, the response rates have been unsatisfactory with progression-free survival of only 2.3 to 6.2 months, and there is an unmet need for an effective treatment for patients with refractory disease.
TAS-102 is a novel combination medicinal product consisting of a thymidine-based nucleoside analogue (trifluridine; FTD) as the active component and the thymidine phosphorylase inhibitor tipiracil hydrochloride (TPI) that has shown promising activity in phase I trials in patients with solid tumors and phase II in patients with gastric cancer. FTD enters cancer cells, interferes with DNA synthesis, inhibits cell proliferation and inhibit tumor growth. TPI helps FTD sustain its level in cells without degradation by thymidine phosphorylase (Tpase).Thus TAS-102 uses dual approach to inhibit rapid degradation of trifluridine and subsequent tumor growth.
Given the safety profile and efficacy, the study is designed to explore/evaluate efficacy of TAS-102 and identify characteristics of patients who may respond to this treatment.
- Being tested
- All patients- TAS-102
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
All patients- TAS-102Drug
Also called Trifluridine, Tipiracil
Patients will receive TAS-102, Orally, BID for 5 days a week with 2 days rest for 14 days, followed by a 14-day rest treatment cycle. Treatment may continue until disease progresses, intolerable toxicity is developed, or if the patient becomes pregnant or dies.
| Study group | Role | What they receive |
|---|---|---|
| TAS-102 | Experimental | Patients will receive TAS-102, Orally, BID for 5 days a week with 2 days rest for 14 days, followed by a 14-day rest treatment cycle. Treatment may continue until disease progresses, intolerable toxicity is developed, or if the patient becomes pregnant or dies. Receives: Drug: All patients- TAS-102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
To assess clinical activity [ORR = Partial response (PR)+Complete response (CR) ] of TAS-102 in patients with metastatic, extra pulmonary high grade NEC
Measured: 24 months
Secondary outcomes (2)
Overall Survival (OS)
To assess OS in patients with metastatic extra pulmonary high grade NEC who received TAS-102 In comparison with historical records.
Measured: 24 months
Progression free survival (PFS)
To assess PFS in patients with metastatic extra pulmonary high grade NEC who received TAS-102 in comparison with historical records
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2019
- Study start15 Aug 2019
- Primary completion15 Sep 2025
- Study completion15 Oct 2025
Why it stopped: Study halted due to low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-grade Extra Pulmonary Neuroendocrine CancerStudies of the same condition, open and under way.
- More trials run by Baylor Research InstituteThe 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
- Model description
- Patients with metastatic high-grade extra pulmonary NEC, who failed front line treatment with a platinum containing regimen, who meets the enrollment criteria will receive TAS-102 as a single agent until either progression or unacceptable toxicity.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Taiho Oncology, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04042714
- Sponsor's protocol ID
- 019-075
- Other IDs
- 019-075
- Acronym
- TAS-102 NEC
- Status last verified
- Jan 2020
- First submitted
- 31 Jul 2019
- Last updated
- 4 Nov 2025
- 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 4 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase II Investigation of TAS-102 in Patients With High Grade, Extrapulmonary Neuroendocrine Carcinoma
- ClinicalTrials.gov ID
- NCT04042714
- Acronym / sponsor ID
- TAS-102 NEC / 019-075
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study halted due to low enrollment
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Baylor Research InstituteUniversity, hospital or other
- Collaborators
- Taiho Oncology, Inc.
- Study start
- 15 Aug 2019 (actual)
- Primary completion
- 15 Sep 2025 (actual)
- Study completion
- 15 Oct 2025 (actual)
- First posted
- 2 Aug 2019 (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.
The purpose of this study is to test the safety and efficacy of drug, TAS-102 (trifluridine/tipiracil), in patients with extrapulmonary (outside the lung) high-grade neuroendocrine cancer. TAS-102 demonstrated improved survival and tolerability in patients with colorectal cancer and is currently approved by the FDA and marketed under the brand name Lonsurf for the treatment of patients with metastatic colorectal cancer (mCRC). Recently, a study evaluating TAS-102 showed a case of complete remission of high-grade NEC. Given the safety profile of TAS-102 and the remarkable single agent activity in a disease with otherwise dismal outcomes, we hope that TAS-102 may show tolerability and efficacy in neuro-endocrine cancer and propose further exploration in patients with extrapulmonary (outside the lung) high-grade neuroendocrine cancer.
Detailed description
Neuroendocrine tumors are highly prevalent cancer showing heterogeneous array of behaviors. For intermediate/high grade and poorly differentiated neuroendocrine carcinomas (NEC) that occur outside the lung, there is no acceptable standard of care. Most patients are treated with a platinum-based chemotherapy in the front-line setting and evidence for therapies in the second line setting is minimal representing a significant unmet need. However, the response rates have been unsatisfactory with progression-free survival of only 2.3 to 6.2 months, and there is an unmet need for an effective treatment for patients with refractory disease.
TAS-102 is a novel combination medicinal product consisting of a thymidine-based nucleoside analogue (trifluridine; FTD) as the active component and the thymidine phosphorylase inhibitor tipiracil hydrochloride (TPI) that has shown promising activity in phase I trials in patients with solid tumors and phase II in patients with gastric cancer. FTD enters cancer cells, interferes with DNA synthesis, inhibits cell proliferation and inhibit tumor growth. TPI helps FTD sustain its level in cells without degradation by thymidine phosphorylase (Tpase).Thus TAS-102 uses dual approach to inhibit rapid degradation of trifluridine and subsequent tumor growth.
Given the safety profile and efficacy, the study is designed to explore/evaluate efficacy of TAS-102 and identify characteristics of patients who may respond to this treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with metastatic high-grade extra pulmonary NEC, who failed front line treatment with a platinum containing regimen, who meets the enrollment criteria will receive TAS-102 as a single agent until either progression or unacceptable toxicity.
| Arm | Type | Receives |
|---|---|---|
| TAS-102 | Experimental | Drug: All patients- TAS-102Patients will receive TAS-102, Orally, BID for 5 days a week with 2 days rest for 14 days, followed by a 14-day rest treatment cycle. Treatment may continue until disease progresses, intolerable toxicity is developed, or if the patient becomes pregnant or dies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Pathologic confirmation of high grade NEC using WHO criteria as determined by Ki67>20%, poorly differentiated (G3) characteristics, or >20 mitotic figures/10 high-power fields.
- Unknown primary may be included. Suspected extrapulmonary patients with known lung primary will be excluded.
- Prior treatment with a platinum containing regimen
- RECIST 1.1 measurable disease
- Evidence of stage IV, metastatic disease
Key exclusion criteria (9 listed)
- Women who are pregnant or breastfeeding.
- Evidence of low-grade or well-differentiated features as determined by the investigator.
- Functional neuroendocrine tumors are excluded.
- Known pulmonary primary or small cell lung cancer will be excluded.
- Significant or uncontrolled congestive heart failure (CHF), myocardial infarction or significant ventricular arrhythmias within the last six 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 |
|---|---|---|
| All patients- TAS-102Also: Trifluridine, TipiracilPatients will receive TAS-102, Orally, BID for 5 days a week with 2 days rest for 14 days, followed by a 14-day rest treatment cycle. Treatment may continue until disease progresses, intolerable toxicity is developed, or if the patient becomes pregnant or dies. | Drug | TAS-102 |
Primary outcome
Overall Response Rate (ORR)
Time frame: 24 months
To assess clinical activity [ORR = Partial response (PR)+Complete response (CR) ] of TAS-102 in patients with metastatic, extra pulmonary high grade NEC
2 secondary outcomes
Overall Survival (OS)
Time frame: 24 months
Progression free survival (PFS)
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Study halted due to low enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2025.
- Individual participant dataSharing planned: No
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.
The record lists no contact. Use the official record to reach the sponsor.
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 All patients- TAS-102 in people with High-grade Extra Pulmonary Neuroendocrine Cancer, run by Baylor Research Institute 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 12 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: stopped early, as of the sponsor's last update on 4 Nov 2025. 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?
The study was stopped early (reason given: Study halted due to low enrollment). Results are not available in the source record.
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?
Overall Response Rate (ORR) (time frame: 24 months). 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 4 Nov 2025.