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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rectal Cancer	Drug: TAS 102; Drug: Oxaliplatin	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: SHORT: SHOrt Course Radiation and TASOX (TAS102 Plus Oxaliplatin) Chemotherapy in Operable Rectal Cancer, a Phase II Trial
• Actual Study Start Date: July 5, 2022
• Actual Primary Completion Date: December 14, 2023
• Actual Study Completion Date: February 21, 2024

Arms and Interventions

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 Name: Tipiracil hydrochloride; Drug: Oxaliplatin; Administered by intravenous infusion over 2 hours on day 1; Other Name: Eloxatin

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

University of California, Irvine

Orange, California, United States, 92868

United States, New York

Columbia University Irving Medical Center/NYPH

New York, New York, United States, 10032

United States, Oregon

Providence Portland Medical Center

Portland, Oregon, United States, 97213

United States, Washington

Virginia Mason Medical Center

Seattle, Washington, United States, 98101

Sponsors and Collaborators

Providence Health & Services

Taiho Oncology

Investigators

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

  Study Documents (Full-Text)

Documents provided by Providence Health & Services:

Study Protocol and Statistical Analysis Plan  [PDF] June 20, 2023

More Information

• Responsible Party: Providence Health & Services
• ClinicalTrials.gov Identifier: NCT04417699
• Other Study ID Numbers: 2021000326
• First Posted: June 5, 2020
• Last Update Posted: March 25, 2024
• Last Verified: March 2024

• 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

Keywords provided by Providence Health & Services:

SHORT; short course radiation,; TASOX

Additional relevant MeSH terms:

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Oxaliplatin; Antineoplastic Agents