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

Must be taking: FOLFOX, CAPOX

Must not be taking: Immunosuppressives, Myelosuppressives

Disqualifiers: Recurrent cancer, Unresectable cancer, Metastatic disease, Neuropathy, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of chemotherapy and radiation therapy to determine the safest dose for treating stage II-III rectal cancer that can be surgically removed. The chemotherapy drug, TAS-102 (Trifluridine and Tipiracil Hydrochloride), aims to stop cancer cells from growing and spreading, while radiation therapy uses high-energy x-rays to shrink tumors. Individuals diagnosed with untreated stage II or III rectal cancer, considered removable by surgery, may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TAS-102, a combination of trifluridine and tipiracil hydrochloride, has been tested for safety in treating various cancers. In studies involving patients with advanced colorectal cancer, TAS-102 was generally well-tolerated. A review of several studies found that it helped patients live longer compared to a placebo, without causing severe side effects.

In another study, combining TAS-102 with bevacizumab was mostly well-tolerated, with most side effects being manageable and not life-threatening. This suggests that TAS-102 is relatively safe for cancer treatment, although some patients might still experience mild to moderate side effects like nausea or tiredness.

Since this trial is in an early phase, it aims to find the safest dose. Researchers continue to gather information on patient responses to the treatment. However, past studies suggest that TAS-102 is generally safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TAS-102 for rectal cancer because it combines a unique chemotherapy blend, trifluridine and tipiracil hydrochloride, with advanced radiation techniques like IMRT (Intensity-Modulated Radiation Therapy) and 3D-CRT (Three-Dimensional Conformal Radiation Therapy). Unlike standard treatments such as FOLFOX or CAPOX, TAS-102 targets cancer cells with a new mechanism that inhibits DNA synthesis, potentially leading to more effective cancer cell destruction. This combination could enhance the precision and effectiveness of treatment, offering hope for improved outcomes in patients with rectal cancer.

What evidence suggests that TAS-102 combined with radiation therapy might be an effective treatment for rectal cancer?

Research has shown that TAS-102, a combination of trifluridine and tipiracil hydrochloride, can benefit people with metastatic colorectal cancer. Studies found that patients taking TAS-102 lived longer and had better disease control compared to those who did not. Specifically, TAS-102 was linked to longer overall survival, more time before cancer progression, and extended periods before needing to change treatments. It also increased the number of patients whose cancer stopped growing or shrank. In this trial, participants will receive TAS-102 alongside either Intensity-Modulated Radiation Therapy (IMRT) or 3-Dimensional Conformal Radiation Therapy (3D-CRT) to evaluate its effectiveness in treating rectal cancer by stopping tumor growth and aiding in disease management. ^{1 2 3 6 7}

Who Is on the Research Team?

Charles D Lopez, MD, PhD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37414979/

Efficacy and safety of trifluridine/tipiracil (TAS-102) in ... In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS- ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214963

Trifluridine–Tipiracil and Bevacizumab in Refractory ... Among patients with refractory metastatic colorectal cancer, treatment with FTD–TPI plus bevacizumab resulted in longer overall survival than FTD–TPI alone.

3. taihooncology.com taihooncology.com/us/news/taiho-oncology-presents-real-world-findings-for-lonsurf-at-the-asco-gastrointestinal-cancers-symposium/

Taiho Oncology Presents Real-World Findings for ... Real-world studies confirm that pairing LONSURF with bevacizumab increases efficacy in patients with metastatic colorectal cancer ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3580

Real-world treatment patterns and outcomes with ... Real-world effectiveness and safety of trifluridine/tipiracil plus bevacizumab in metastatic colorectal cancer: A retrospective observational ...

5. foxchase.org foxchase.org/news/fox-chase-cancer-center-researcher-shows-biweekly-dose-tas-102-reduces-toxicity-and-remains

Fox Chase Cancer Center Researcher Shows Biweekly ... Patients with metastatic colorectal cancer who were treated with a biweekly dose of trifluridine-tipiracil (TAS-102) saw similar treatment effectiveness and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11067808/

Efficacy and Safety of Trifluridine/Tipiracil-Containing ... Median overall survival ranged 8.6-14.4 months and median progression-free survival 3.7-6.8 months with FTD/TPI plus bevacizumab in refractory ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.51

Real-world effectiveness and safety of trifluridine-tipiracil ... Among 97 evaluable patients, the overall response rate (ORR) was 2.1%, and the disease control rate (DCR) was 46.4%. With a median follow-up of ...