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

• ClinicalTrials.gov Identifier: NCT04417699
• Recruitment Status: Completed
• First Posted: June 5, 2020
• Last Update Posted: March 25, 2024
• Sponsor: Providence Health & Services
• Collaborator: Taiho Oncology
• Information provided by (Responsible Party): Providence Health & Services

Tracking Information

• First Submitted Date: May 15, 2020
• First Posted Date: June 5, 2020
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: July 5, 2022
• Actual Primary Completion Date: December 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2020)

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 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 2, 2020)

Safety and Tolerability [ Time Frame: Through study completion, an average of 6 months ]

The secondary objective is to describe Incidence of Treatment-Emergent Adverse Events and surgery complications among treated subjects.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rectal Cancer

Intervention

• Drug: TAS 102
  Oral medication over Days 1-5
  Other Name: Tipiracil hydrochloride
• Drug: Oxaliplatin
  Administered by intravenous infusion over 2 hours on day 1
  Other Name: Eloxatin

Study Arms

Experimental: TAS102 plus Oxaliplatin

Oxaliplatin 85mg/m2 IV over 2 hours and TAS-102 (35 mg/m2/dose) orally BID

Interventions:

• Drug: TAS 102
• Drug: Oxaliplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 24, 2024): 13
• Original Estimated Enrollment (submitted: June 2, 2020): 27
• Actual Study Completion Date: February 21, 2024
• Actual Primary Completion Date: December 14, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04417699
• Other Study ID Numbers: 2021000326
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Providence Health & Services
• Original Responsible Party: Benaroya Research Institute
• Current Study Sponsor: Providence Health & Services
• Original Study Sponsor: Benaroya Research Institute
• Collaborators: Taiho Oncology

Investigators

• Principal Investigator: Hagen Kennecke, MD; Providence Health & Services

• PRS Account: Providence Health & Services
• Verification Date: March 2024