Clinical Trials /

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

NCT04417699

Description:

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.

Related Conditions:
  • Rectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CRP18085
  • NCT ID: NCT04417699

Conditions

  • Rectal Cancer

Interventions

DrugSynonymsArms
TAS 102TAS102 plus Oxaliplatin
OxaliplatinTAS102 plus Oxaliplatin

Purpose

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

      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).
    

Trial Arms

NameTypeDescriptionInterventions
TAS102 plus OxaliplatinExperimentalOxaliplatin 85mg/m2 IV over 2 hours and TAS-102 (35 mg/m2/dose) orally BID
  • TAS 102
  • Oxaliplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Age of at least 18 years.

          2. Newly diagnosis of rectal adenocarcinoma.

          3. ECOG Performance Status (PS): 0, 1 or 2.

          4. Candidate for sphincter-sparing surgical resection prior to initiation of neoadjuvant
             therapy according to the primary surgeon.

          5. Clinical Stage: T1/N1, T2/N1, T3/N1, T3c/dN0.

          6. 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.

          7. 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

          8. 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

          9. Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing
             potential only.

         10. 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

         11. Provide informed written consent.

         12. Willing to return to enrolling medical site for all study assessments.

        Exclusion Criteria:

          1. Clinical T4 tumors.

          2. Clinical N2 disease estimated as four or more lymph nodes that are ≥8 mm.

          3. Primary surgeon indicates need for abdominoperineal (APR) at baseline.

          4. 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.

          5. Tumor is causing symptomatic bowel obstruction or patients who have had a temporary
             diverting ostomy are ineligible.

          6. Chemotherapy within 5 years prior to registration. (Hormonal therapy is allowable if
             the disease free interval is ≥ 5 years.)

          7. Any prior pelvic radiation.

          8. 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

          9. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Achieve a reduction by at least 5.8 in Neoadjuvant Response (NAR) score compared to historic controls with NAR of 14.59
Time Frame:Through study completion, an average of 6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Benaroya Research Institute

Trial Keywords

  • SHORT
  • short course radiation,
  • TASOX

Last Updated

June 2, 2020