- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04042714
TAS-102 in Extrapulmonary Neuroendocrine Carcinoma (TAS-102 NEC)
An Open-label, Phase II Investigation of TAS-102 in Patients With High Grade, Extrapulmonary Neuroendocrine Carcinoma
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
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Dallas, Texas, United States, 75246
- Recruiting
- Baylor Scott and White University Medical Center,
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Principal Investigator:
- Scott Paulson, MD
-
Contact:
- Preethi Ravindranathan, MS
- Phone Number: 214-820-8685
- Email: preethi.ravindranathan@bswhealth.org
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Contact:
- Silviya Meletath, MBBS
- Phone Number: 214-820-4987
- Email: Silviya.Meletath@BSWHealth.org
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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).
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TAS-102
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.
|
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 24 months
|
To assess OS in patients with metastatic extra pulmonary high grade NEC who received TAS-102 In comparison with historical records.
|
24 months
|
Progression free survival (PFS)
Time Frame: 24 months
|
To assess PFS in patients with metastatic extra pulmonary high grade NEC who received TAS-102 in comparison with historical records
|
24 months
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Carcinoma, Neuroendocrine
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Trifluridine
Other Study ID Numbers
- 019-075 (Other Identifier: Baylor Scott and White Research Institute)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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