TAS-102 + Oxaliplatin for Colon Cancer

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Investigational agents

Disqualifiers: Peripheral neuropathy, CNS metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Ongoing until disease progression or unacceptable toxicity

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other investigational agents or have had anticancer therapy within the last 3 weeks before starting the study.

What data supports the effectiveness of the drug TAS-102 combined with Oxaliplatin for colon cancer?

Research shows that TAS-102, when used alone, extended the survival of patients with advanced colorectal cancer by about 2 months compared to a placebo. Additionally, combining TAS-102 with Oxaliplatin has been shown in early studies to enhance anti-tumor activity compared to using either drug alone. ^{1 2 3 4 5}

Is the combination of TAS-102 and Oxaliplatin safe for humans?

TAS-102, also known as Lonsurf, has been studied for safety in patients with colorectal cancer. While it can cause side effects like neutropenia (a drop in white blood cells), these were managed with supportive care, and no hospitalizations were reported due to treatment-related issues. ^{1 2 6 7 8}

What makes the drug TAS-102 + Oxaliplatin unique for colon cancer treatment?

The combination of TAS-102 and Oxaliplatin is unique because it combines a novel platinum-based drug, Oxaliplatin, which is effective even in tumors resistant to other platinum drugs, with TAS-102, a mixture that includes trifluridine, which interferes with cancer cell DNA, and tipiracil, which helps maintain trifluridine levels. This combination may offer a new option for patients who have not responded to other treatments. ^{9 10 11 12 13}

What is the purpose of this trial?

This phase II trial studies how well TAS-102 and oxaliplatin work in treating patients with stage IV colon cancer. Drugs used in chemotherapy, such as TAS-102 and oxaliplatin, 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.

Research Team

Howard S. Hochster

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for adults with stage IV colon cancer that's worsened after standard treatment. They should have had a reaction to previous treatments, measurable disease, specific genetic features (RAS mutation and MMR status), good physical function, and acceptable blood counts. They must not be pregnant or breastfeeding, have no major recent surgery or active infections, and can't have used TAS-102 before.

Inclusion Criteria

My stage IV colon cancer has worsened after standard treatment.

I stopped my cancer treatment due to severe side effects.

Progression of disease must be documented on the most recent scan

Exclusion Criteria

Pregnancy or breast feeding

I haven't had cancer treatment in the last 3 weeks.

You have had allergic reactions to similar medications like TAS-102 in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAS-102 orally twice daily on days 1-5 and oxaliplatin intravenously on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Ongoing until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Oxaliplatin
• TAS-102

Trial Overview The study tests how well TAS-102 combined with oxaliplatin works in treating advanced colon cancer. It's a phase II trial where these chemotherapy drugs are given to see if they can stop cancer cells from growing by killing them or preventing their spread.

Participant Groups

Group I: Treatment (TAS-102, oxaliplatin) Experimental Treatment 2 Interventions

Patients receive TAS-102 PO BID on days 1-5 and oxaliplatin IV over 2 hours on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Oxaliplatin is already approved in European Union, United States, Canada, Japan, Switzerland, China for the following indications:

Approved in European Union as Eloxatin for:

• Colorectal cancer

Approved in United States as Eloxatin for:

• Colorectal cancer

Approved in Canada as Eloxatin for:

• Colorectal cancer

Approved in Japan as Eloxatin for:

• Colorectal cancer

Approved in Switzerland as Eloxatin for:

• Colorectal cancer

Approved in China as Ai Heng for:

• Colorectal cancer

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 32 Chinese patients with metastatic colorectal cancer, the test formulation of trifluridine and tipiracil (FTD/TPI) was found to be bioequivalent to the reference formulation (Lonsurf®), indicating similar effectiveness and safety profiles.

The pharmacokinetic parameters, including maximum plasma concentration and area under the curve, for both formulations fell within the FDA's bioequivalence criteria, confirming that the test formulation can be used interchangeably with Lonsurf® in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A bioequivalence study of trifluridine/tipiracil tablets in Chinese metastatic colorectal cancer patients under fed conditions. Su, HC., Min, J., Song, Y., et al.[2023]

In a study of 70 patients with metastatic colorectal cancer who had previously failed multiple therapies, TAS-102 demonstrated a median progression-free survival (PFS) of 6.0 months and an overall survival (OS) of 10.0 months, indicating its effectiveness in a real-world setting.

Combining TAS-102 with bevacizumab resulted in significantly better disease control rates (75.9% vs. 40-50% for other combinations), PFS (6.3 months vs. 3.0 months), and OS (12.0 months vs. 6.0-6.5 months), suggesting that this combination therapy may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study. Nie, C., Xu, W., Chen, B., et al.[2023]

Oxaliplatin is a promising treatment for colorectal cancer (CRC) that works well in combination with 5-fluorouracil (5-FU), even in cases where tumors are resistant to 5-FU, as shown in controlled phase III trials.

With its excellent safety profile and unique mechanism of action, oxaliplatin can be effectively combined with other chemotherapy agents, and ongoing studies aim to optimize its use in CRC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin: a new therapeutic option in colorectal cancer. Cvitkovic, E., Bekradda, M.[2022]

Oxaliplatin is a potent antineoplastic drug that works by blocking DNA replication and transcription, leading to cell death, and has shown greater efficacy than other platinum-based drugs like cisplatin in preclinical studies.

It is approved for treating metastatic colorectal cancer in several regions and shows promise in combination therapies with other agents, enhancing its effectiveness against various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel combinations with oxaliplatin. Mani, S., Manalo, J., Bregman, D.[2022]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Trifluridine-Tipiracil Hydrochloride Oral Combination (TAS-102) in Patients with Unresectable Colorectal Cancer. [2020]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in patients with metastatic colorectal cancer. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

A bioequivalence study of trifluridine/tipiracil tablets in Chinese metastatic colorectal cancer patients under fed conditions. [2023]

5. 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]

6. 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]

7. Greece pubmed.ncbi.nlm.nih.gov

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

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

An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study. [2023]

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

Oxaliplatin: a new therapeutic option in colorectal cancer. [2022]

10. India pubmed.ncbi.nlm.nih.gov

Review of oxaliplatin: an active platinum agent in colorectal cancer. [2018]

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

Novel combinations with oxaliplatin. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Successful oxaliplatin desensitization protocol in a patient with colorectal metastatic cancer. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Integrating oxaliplatin into the management of colorectal cancer. [2019]