SHOrt Course Radiation and TASOX (TAS102 Plus Oxaliplatin) Chemotherapy in Operable Rectal Cancer

Study Overview
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Brief Summary
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TASOX can be safely and efficaciously delivered after short course radiation, resulting in significant pathologic downstaging, allowing for an R0 pelvic resection, and providing local control in appropriately selected stage II/III rectal cancer patients treated with contemporary TME-based surgery.

Detailed Description
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In this phase II study patients will be treated with short-course preoperative irradiation (25 Gy in five fractions of 5 Gy) followed by 6 (six) 2-week cycles of TASOX followed by total mesorectal excision (TME) for patients with resectable rectal cancer (clinical T3c/dN0, T3c/dN1, T2N1). Eligible study subjects include adults who are candidates for curative intent sphincter-sparing surgery and lack high risk features such as tumor encroaching upon the mesorectal-fascia or low tumors who need an Abdominal-Perineal Resection (APR).

Official Title
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SHORT: SHOrt Course Radiation and TASOX (TAS102 Plus Oxaliplatin) Chemotherapy in Operable Rectal Cancer, a Phase II Trial

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: TAS 102
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of at least 18 years. Newly diagnosis of rectal adenocarcinoma. ECOG Performance Status (PS): 0, 1 or 2. Candidate for sphincter-sparing surgical resection prior to initiation of neoadjuvant therapy according to the primary surgeon. Clinical Stage: T1/N1, T2/N1, T3/N1, T3c/dN0. Absence of metastatic disease. Clinical staging is based on physical exam by the primary surgeon, CT scan of the chest/abdomen, and pelvic MRI. Node positivity determination: Entry criteria nodes will be measured in short-axis diameter and for the purposes of study entry will be considered positive if 8 mm or greater in short axis. Radiographic N2 status is estimated as: 4 or more nodes that measure 8mm or more in short-axis. Radiographic N1 status is estimated as: fewer than 4 lymph nodes that measure 8 mm or greater in short axis but 1 or more lymph nodes that measure 8 mm or greater. Nodal Metastatic Disease: nodal stations considered suspicious for metastatic disease (M1) for rectal cancer are common iliac, external iliac and inguinal nodes. No evidence of tumor that is adherent to the mesorectal fascia and the ability to perform a curative intent sphincter-sparing TME resection at diagnosis. See exclusion criterion 4 The following laboratory values obtained ≤ 28 days prior to registration. Platelet count ≥ 100,000/mm^3 Hemoglobin > 8.0 g/dL Total bilirubin ≤ 1.5 x upper limit of normal (ULN) SGOT (AST) ≤ 3 x ULN SGPT (ALT) ≤ 3 x ULN Creatinine ≤1.5 x ULN Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only. A patient of child-bearing potential is willing to employ adequate contraception. It includes any of the followings: abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom). See exclusion criterion 8 Provide informed written consent. Willing to return to enrolling medical site for all study assessments. Exclusion Criteria: Clinical T4 tumors. Clinical N2 disease estimated as four or more lymph nodes that are ≥8 mm. Primary surgeon indicates need for abdominoperineal (APR) at baseline. Evidence that the tumor is adherent to or invading the mesorectal fascia on imaging studies such that the surgeon would not be able to perform an R0 resection (one with negative margins). Distance of the Tumor from the Mesorectal Fascia: Patients with tumors with a distance of 1mm or less from the mesorectal fascia reflection have threatened radial margins and are ineligible. Tumor is causing symptomatic bowel obstruction or patients who have had a temporary diverting ostomy are ineligible. Chemotherapy within 5 years prior to registration. (Hormonal therapy is allowable if the disease free interval is ≥ 5 years.) Any prior pelvic radiation. Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Co-morbid illnesses or other concurrent disease which, in the judgment of the treating investigator obtaining informed consent, 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.

Ages Eligible for Study
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Minimum Age: 18 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: TAS102 plus Oxaliplatin<br>Oxaliplatin 85mg/m2 IV over 2 hours and TAS-102 (35 mg/m2/dose) orally BID | Drug: TAS 102<br>* Oral medication over Days 1-5<br>* Other names: Tipiracil hydrochloride;Drug: Oxaliplatin<br>* Administered by intravenous infusion over 2 hours on day 1<br>* Other names: Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achieve a reduction by at least 5.8 in Neoadjuvant Response (NAR) score compared to historic controls with NAR of 14.59 | determine whether pre-operative short-course radiation therapy (SRT) and 6 cycles of TASOX offers condensed radiation and total neoadjuvant therapy for intermediate risk rectal cancer. | Through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | The secondary objective is to describe Incidence of Treatment-Emergent Adverse Events and surgery complications among treated subjects. | Through study completion, an average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHORT, short course radiation,, TASOX