TAS-102 With Concurrent Radiation for the Treatment of Untreated Resectable Stage II-III Rectal Cancer

NCT04104139 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: STUDY00019576NCI-2019-06387SOL-19069-L
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1b trial studies the side effects and best dose of TAS-102 when given together with radiation therapy in treating patients with stage II-III rectal cancer that has not been treated and can be removed by surgery (resectable). Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study is being done to find out the safest dose of TAS-102 that can be used with radiation treatment for rectal cancer.

Conditions

Rectal Adenocarcinoma; Stage IIA Rectal Cancer AJCC v8; Stage IIB Rectal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Stage IIIA Rectal Cancer AJCC v8; Stage IIIB Rectal Cancer AJCC v8; Stage IIIC Rectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Proportion of dose limiting toxicity (DLT)s for TAS-102 at the maximum tolerated dose (MTD)

  Will be assessed through the Bayesian optimal interval design and will be determined by the proportion of grade 3 or higher adverse events during chemo-radiation therapy (CRT) with TAS-102 at the MTD by allowing no more than 30% DLT. The proportion will be descriptively noted.

  Up to end of week 8, or start of fluorouracil/leucovorin calcium/oxaliplatin (FOLFOX) or capecitabine/oxaliplatin (CAPOX) chemotherapy, whichever occurs first

Secondary Outcomes (2)

• Incidence of adverse events (AEs) (all grade) for TAS-102 concurrent with radiation therapy (RT)

  Up to start of FOLFOX or CAPOX (up to 8 weeks)

• Incidence of grade 3 or higher treatment emergent adverse events (TEAEs) during FOLFOX or CAPOX treatment

  Up to end of FOLFOX or CAPOX (up to 16 weeks)

Other Outcomes (7)

• Rate of complete response (CR) by magnetic resonance imaging (MRI) after chemo-radiation therapy (CRT)

  Prior to starting FOLFOX or CAPOX regimen (up to 8 weeks)

• Rate of CR by endoscopic exam after CRT

  Prior to starting FOLFOX or CAPOX regimen (up to 8 weeks)

• Rate of clinical complete response (cCR) by MRI and endoscopic response after CRT

  Prior to starting FOLFOX or CAPOX regimen (up to 8 weeks)

Study Arms (1)

Treatment (TAS-102, IMRT, 3D-CRT)

EXPERIMENTAL

Patients receive TAS-102 PO BID Monday-Friday on weeks 1, 3, and 5. Patients also undergo IMRT or 3D-CRT 5 days per week on weeks 1-5. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care FOLFOX or CAPOX.

Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Drug: Trifluridine and Tipiracil Hydrochloride

Interventions

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Treatment (TAS-102, IMRT, 3D-CRT)

Trifluridine and Tipiracil Hydrochloride DRUG

Given PO

Also known as: Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102

Treatment (TAS-102, IMRT, 3D-CRT)

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo 3D-CRT

Also known as: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy, Radiation, 3D Conformal

Treatment (TAS-102, IMRT, 3D-CRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All races and ethnic groups will be included
• Histologically confirmed diagnosis of adenocarcinoma of the rectum
• Clinical stage II (T3-4aN0M0) and stage III (T1-4aN1+M0) based on MRI
• Resectable primary rectal tumor at baseline
• No evidence of distant metastases
• No prior pelvic radiation therapy
• No prior chemotherapy or surgery for rectal cancer
• No active infections requiring systemic antibiotic treatment (oral antibiotics are acceptable at the discretion of the treating physician)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Leukocytes \>= 3,000/uL
• Absolute neutrophil count \>= 1,500/uL
• Hemoglobin \>= 9.0 gm/dL
• Platelets \>= 100,000/uL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN)

You may not qualify if:

• Recurrent rectal cancer
• Primary unresectable rectal cancer. A tumor is considered unresectable when invading adjacent organs (T4b disease) and an en bloc resection will not achieve negative margins. Rectal cancer presenting with concurrent or overlapping sites in the colon is eligible if these sites could be removed with surgery
• Distant nodal disease (retroperitoneal nodes), or any metastatic disease by computed tomography (CT) or positron emission tomography (PET)
• Creatinine \> 1.5 x ULN
• History of peripheral neuropathy \> grade 2
• History of malabsorption syndromes or inflammatory bowel disease
• Use of immunosuppressive or myelosuppressive medications including but not limited to adalimumab, azathioprine, BCG, clozapine, cyclosporine, deferiprone, etanercept, fingolimod, hydroxyurea, interferon, leflunomide, methotrexate, mycophenolate, natalizumab, pimecrolimus, rituximab, sirolimus, and tacrolimus
• Inability to take oral medications
• Participants who received prior pelvic radiotherapy
• Use of induction chemotherapy prior to chemo-radiation of rectal cancer
• Use of other chemotherapy regimens other than FOLFOX or CAPOX
• Participants who are unable to undergo an MRI
• Participants who are unable to undergo TME
• Refusal of standard-of-care TME of the rectal tumor if there is persistent disease after neoadjuvant treatment
• Participants with a history of any arterial thrombotic event within the past 6 months, including angina (stable or unstable), myocardial infarction (MI), transient ischemic attack (TIA), or cerebrovascular accident (CVA)

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Taiho Pharmaceutical Co., Ltd.: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Chen EY, Nabavizadeh N, Kendsersky ND, Lessenich C, Herzig DO, Korngold E, Goodyear SM, Kennecke HF, Kardosh A, Tsikitis VL, Lu KC, Fang S, Wong M, Pegna GJ, Rocha FG, Mayo SC, Brinkerhoff B, Taber E, Rajagopalan B, Park BS, Thomas CR Jr, Lopez CD. Phase Ib Study to Assess the Safety of Neoadjuvant Trifluridine/Tipiracil With Concurrent Radiation in Resectable Stage II/III Rectal Cancer: The FIERCE Study. Clin Colorectal Cancer. 2026 Feb 4:S1533-0028(26)00008-3. doi: 10.1016/j.clcc.2026.02.001. Online ahead of print.

  PMID: 41781240 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Trifluridine; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Charles D Lopez, MD, PhD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: September 26, 2019
• Study Start: December 11, 2019
• Primary Completion: September 25, 2024
• Study Completion (Estimated): May 31, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)