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

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

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.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: TAS 102; Drug: Oxaliplatin

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).

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center/NYPH
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAS102 plus Oxaliplatin; Oxaliplatin 85mg/m2 IV over 2 hours and TAS-102 (35 mg/m2/dose) orally BID	Drug: TAS 102; Oral medication over Days 1-5; Other Names: Tipiracil hydrochloride; Drug: Oxaliplatin; Administered by intravenous infusion over 2 hours on day 1; Other Names: Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neoadjuvant Response (NAR) Score	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. Measurement of efficacy is the NAR score, where the required elements of the NAR score are: clinical tumor stage (cT), pathologic tumor stage (pT), pathological nodal stage (pN). For patients with a cCR who opted for non-operative management, for the purposes of the NAR score, those patients were assigned a pT0 and pN0 score if they did not experience tumor regrowth or require subsequent TME surgical resection during the time of the study. The NAR score ranges from 0-100, where lower NAR scores are considered favorable as opposed to higher scores which would indicate a worse prognosis. NAR calculation as follows: NAR=[5 pN- 3(cT-pT)+12]^2/9.61	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

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Taiho Oncology
• Investigators: Principal Investigator: Hagen Kennecke, MD, Providence Health & Services

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): February 21, 2024

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: SHORT; short course radiation,; TASOX
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Organic Chemicals; Coordination Complexes; Oxaliplatin; trifluridine tipiracil drug combination
• Other Study ID Numbers: 2021000326

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes