TAS-102 + Radiation for Rectal Cancer

Overseen By OHSU Knight Cancer Clinical Trials Hotline

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: OHSU Knight Cancer Institute

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 5 weeks

19 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are using certain immunosuppressive or myelosuppressive medications, or if you have had recent thrombotic events unless on stable anticoagulant therapy.

What data supports the effectiveness of the drug TAS-102 for rectal cancer?

TAS-102, a drug used for metastatic colorectal cancer, has been shown to improve overall survival and progression-free survival in patients who are not responding to standard treatments. This suggests it could be a promising option for rectal cancer as well, given its effectiveness in a similar type of cancer. ^{1 2 3 4 5}

Is TAS-102 (Lonsurf) safe for use in humans?

TAS-102 (Lonsurf) has been used in patients with advanced colorectal cancer, and while it can cause side effects like neutropenia (a drop in white blood cells), these were managed with supportive care and did not require hospitalization in the studies reviewed. ^{1 2 6 7 8}

How is the drug TAS-102 unique for treating rectal cancer?

TAS-102, a combination of trifluridine and tipiracil hydrochloride, is unique because it is an oral medication originally used for metastatic colorectal cancer, offering a new option for patients who have not responded to standard treatments. Its combination with radiation for rectal cancer is novel, as it has primarily been used in later stages of colorectal cancer. ^{1 2 9 10 11}

Research Team

Charles D Lopez, MD, PhD

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

This trial is for adults with stage II-III rectal cancer that hasn't spread, can be surgically removed, and who haven't had prior treatments. Participants must have good organ function, no serious infections or recent heart issues, and not be pregnant or breastfeeding. They should agree to use contraception and be able to take oral meds.

Inclusion Criteria

I am scheduled for specific chemotherapy that needs a central line.

I agree to use effective birth control during and for 6 months after the study.

My condition is a type of rectal cancer called adenocarcinoma.

Exclusion Criteria

I am not pregnant or breast-feeding.

I have had blood clots or am on stable blood thinner medication.

I have not had any cancer except for certain skin cancers or cervical cancer in situ in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAS-102 orally twice daily and undergo radiation therapy for 5 weeks

5 weeks

5 visits per week (in-person)

Chemotherapy

Participants undergo standard of care FOLFOX or CAPOX chemotherapy

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Intensity-Modulated Radiation Therapy
• Trifluridine and Tipiracil Hydrochloride

Trial Overview The study tests the safety and best dose of TAS-102 chemotherapy combined with radiation therapy (either intensity-modulated or 3-dimensional conformal) in patients with resectable rectal cancer. The goal is to find out how well this combo works before surgery.

Participant Groups

Group I: Treatment (TAS-102, IMRT, 3D-CRT) Experimental Treatment 3 Interventions

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.

Trifluridine and Tipiracil Hydrochloride is already approved in United States, Japan, European Union for the following indications:

Approved in United States as Lonsurf for:

• Metastatic colorectal cancer
• Metastatic gastric or gastroesophageal junction adenocarcinoma

Approved in Japan as Lonsurf for:

• Metastatic colorectal cancer
• Metastatic gastric or gastroesophageal junction adenocarcinoma

Approved in European Union as Lonsurf for:

• Metastatic colorectal cancer
• Metastatic gastric or gastroesophageal junction adenocarcinoma

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Taiho Pharmaceutical Co., Ltd.

Industry Sponsor

Trials

67

Recruited

18,600+

Masayuki Kobayashi

Taiho Pharmaceutical Co., Ltd.

Chief Executive Officer since 2012

Background in political and law studies

Harold Keer

Taiho Pharmaceutical Co., Ltd.

Chief Medical Officer since 2024

MD

Findings from Research

Trifluridine/tipiracil (TAS-102) has a favorable safety profile for patients with metastatic colorectal cancer (mCRC), showing a low incidence of common adverse events like nausea, diarrhea, and fatigue, which can help improve patient adherence to treatment.

Oncology nurses play a crucial role in educating patients about managing treatment-related adverse events, which is essential for maintaining adherence to this oral chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic Colorectal Cancer: Management With Trifluridine/Tipiracil . White, T., Larson, H., Minnella, A., et al.[2017]

In a study involving 549 patients with metastatic colorectal cancer (mCRC) who had previously undergone standard therapies, trifluridine/tipiracil (FTD/TPI) demonstrated a safety and tolerability profile similar to that observed in the phase III RECOURSE trial.

The treatment was well tolerated in both elderly (≥ 65 years) and younger (< 65 years) patients, indicating that FTD/TPI can be a viable option for elderly patients with mCRC without unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trifluridine/tipiracil in an open-label expanded-access program in elderly and younger patients with metastatic colorectal cancer. Mayer, RJ., Hochster, HS., Cohen, SJ., et al.[2020]

The combination of trifluridine/tipiracil (TAS-102) and bevacizumab is a feasible treatment option for patients with recurrent colorectal cancer, as demonstrated in two case studies.

No severe adverse events (≥Grade 3) were reported, aside from hematotoxicity, indicating a relatively safe profile for this late-line chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab]. Maeda, F., Gan, S., Yamada, A., et al.[2021]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Initial Evaluation of the Efficacy and Safety of Tablets Containing Trifluridine and Tipiracil Hydrochloride--Safety Measures Devised by a Multidisciplinary Team Including a Pharmaceutical Outpatient Clinic]. [2015]

2. Japan pubmed.ncbi.nlm.nih.gov

Effects and risk factors of TAS-102 in real-world patients with metastatic colorectal cancer, EROTAS-R study. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Trifluridine/Tipiracil: A Review in Metastatic Colorectal Cancer. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Tolerability of Trifluridine/Tipiracil Combination Tablet in Patients With Advanced/Recurrent Colorectal Cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety profile of trifluridine/tipiracil monotherapy in clinical practice: results of the German compassionate-use program for patients with metastatic colorectal cancer. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Metastatic Colorectal Cancer: Management With Trifluridine/Tipiracil . [2017]

8. Germany pubmed.ncbi.nlm.nih.gov

Safety of trifluridine/tipiracil in an open-label expanded-access program in elderly and younger patients with metastatic colorectal cancer. [2020]

9. England pubmed.ncbi.nlm.nih.gov

TAS-102 in metastatic colorectal cancer (mCRC): efficacy, tolerability, and quality of life in heavily pretreated elderly patients: a real-life study. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab]. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

TAS-102 (Lonsurf) for the Treatment of Metastatic Colorectal Cancer. A Concise Review. [2020]