TAS-102 (Lonsurf) in Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma Post First Line Chemotherapy (UF-STO-PANC-003)

Study Overview
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Brief Summary
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This is an open-label, non-randomized, sequentially enrolling single arm phase II trial to evaluate the activity of TAS-102 in previously treated metastatic and locally advanced unresectable pancreatic cancer after progression through or intolerance to first or second line chemotherapy. Trial therapy will consist of TAS-102 (Lonsurf®) 35 mg/m2 to be given orally twice daily on days 1-5 and 8-12 with cycles repeating every 28 days. The primary endpoint is to determine the progression free survival (PFS) in subjects with unresectable pancreatic adenocarcinoma.

Official Title
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A Phase II Trial of TAS-102 (Lonsurf) in Patients With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma After Progression Through First Line Chemotherapy

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: TAS-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of adenocarcinoma of the pancreas, with pathologic confirmation of adenocarcinoma. Measurable disease per RECIST 1.1 criteria Metastatic or locally advanced unresectable disease. Subjects without clear evidence of distant metastatic disease will be presented at multidisciplinary tumor board for discussion of disease resectability. Refractory or intolerant to 1 or 2 prior regimens of standard chemotherapy for metastatic or locally advanced pancreatic cancer TAS102 will be planned to start after disease progression on first-or second line chemotherapy, provided any prior chemotherapy-related toxicities have resolved to less than or equal to Grade 1 or baseline within 28 days of the date the subject signs the informed consent form. Grade 2 or greater toxicities including alopecia, skin pigmentation,and platinum induced neurotoxicity/neuropathy are acceptable for starting on trial, as these toxicities do not preclude treatment with TAS102 ECOG Performance Status of 0-2 Capacity to understand and sign the informed consent document Able to take medications orally Life expectancy at least 12 weeks Age at least 18 years Patients on anticoagulation need to have no evidence of uncontrolled bleeding and be on a stable anticoagulation dose for at least 2 weeks prior to the date the subject starts study drug. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 3 months after the last dose of study drug to minimize the risk of pregnancy. Prior to signing the informed consent form, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL. Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 3 months following the last dose of study drug. Baseline laboratory values (bone marrow, renal, hepatic) must include: Adequate bone marrow function: Absolute neutrophil count >1500/mm3 Platelet count >75,000/mm3 HGB equal to or greater than 7g/dL Renal function: a. Serum creatinine ≤ 1.5 mg Hepatic function: Total bilirubin ≤ 1.5 mg/dL AST and ALT equal to or less than 3 times the upper limit of normal for patients without hepatic involvement, or AST and ALT equal to or less than 5 times the upper limit of normal for patients with hepatic involvement Serum calcium ≤ 12 mg/dl Exclusion Criteria: Pregnant or lactating females Previously taken TAS-102 Myocardial infarction or ischemia within the 6 months before first dose of study drug Uncontrolled' clinically significant dysrhythmia Intervention for ascites or pleural effusions within 4 weeks before first dose of study drug Previous surgery and/or radiotherapy may have been performed 2 or more weeks prior to the date the subject starts study treatment, provided that it was to a non-target lesion and there is still evidence of target lesion disease progression radiographically or intolerance to first- or second-line chemotherapy. Major surgery within 4 weeks before first dose of study drug (the surgical incision should be fully healed prior to study medication administration). Any anticancer therapy within 3 weeks before first dose of study drug. Extended field radiation within 4 weeks before first dose of study drug or limited field radiation within 2 weeks before first dose of study drug. Any investigational agent received within prior 4 weeks before first dose of study drug Subjects must not have more than one active malignancy at the time of enrollment Unresolved NCI-CTCAE toxicity grade 2 or higher attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity) Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications including but not limited to chronic infections, uncontrolled diabetes, congestive heart failure according to the NYHA criteria, untreated brain metastases, liver or renal failure, gastrointestinal hemorrhage. Known untreated or unstable brain metastases or leptomeningeal disease Active infection Prisoners or subjects who are involuntarily incarcerated or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>TAS-102 | Drug: TAS-102<br>* TAS-102 (35 mg/m2/dose) orally 2 times daily beginning the morning of Day 1 of each cycle and ending the evening of Day 5 of each cycle, as well as beginning the morning of Day 8 and ending the evening of Day 12 of each cycle. No TAS-102 will be given on Days 6-7 or Days 13-28 of each cycle.<br>* Other names: Lonsurf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | To determine the progression free survival (PFS), which is defined as the duration of time from study entry to disease progression, death, or the date of last contact, whichever occurred first. Subjects were not included in the data for this outcome measure if they went off study for reasons other than disease progression, death or being lost to follow-up. | up to 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | To determine the objective response rate (ORR) by RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 criteria. ORR is defined as the percentage of subjects who attained either a complete or partial response (CR + PR) by RECIST v1.1 criteria. RECIST v1.1 criteria defines a partial response (PR) as a decrease of the sum of the largest diameters of each target lesion by at least 30%. A complete response (CR) is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). | 6 months | 
| Clinical Benefit Rate | To determine the Clinical Benefit Rate, defined as the percent of evaluable subjects who achieved either a complete or partial response or stable disease per RECIST v1.1 criteria. RECIST v1.1 criteria defines a partial response as a decrease of the sum of the largest diameter of each target lesion by at least 30%. A complete response is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). By RECIST v1.1 criteria, a subject is considered to have stable disease when the sum of the largest diameter of the target lesions has neither decreased enough to qualify as a partial response not increased enough to qualify as progressive disease. | 6 months | 
| Time to Progression (TTP) | To determine the time to progression (TTP), defined as the duration of time from study entry to disease progression | up to 54 weeks | 
| Overall Survival (OS) | To determine overall survival (OS), defined as the duration of time from study entry to time of death. | up to 84 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, pancreatic, adenocarcinoma