Combination Chemotherapy for Colorectal Cancer

No longer recruiting at 3 trial locations

Overseen By Namrata Vijayvergia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Anti-cancer therapy

Disqualifiers: Hypertension, Heart failure, Thrombosis, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of three treatments: TAS-102 (Lonsurf), irinotecan (Camptosar), and bevacizumab (Avastin), to determine their combined effectiveness against metastatic colorectal cancer. The goal is to assess whether these drugs, which inhibit cancer cell growth and spread, outperform traditional treatments. This study may suit individuals with advanced colorectal cancer that has resisted previous treatments and cannot be surgically removed. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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 have had anti-cancer therapy within 2 weeks before starting the study medication. It's best to discuss your current medications with the trial team.

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

Research has shown that the combination of TAS-102, irinotecan, and bevacizumab is generally well-tolerated by patients with advanced colorectal cancer. Studies have reported promising effectiveness, with most patients managing the side effects.

One study noted this combination for its promising effectiveness and manageable side effects, indicating that while side effects exist, they are not severe for most and can be managed with medical care. Another study highlighted that adding bevacizumab to TAS-102 improved survival rates compared to TAS-102 alone, without significantly increasing side effects.

Overall, the treatment appears safe for further testing and is considered manageable for trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of bevacizumab, irinotecan, and TAS-102 for colorectal cancer because it represents a novel approach by integrating multiple mechanisms. Bevacizumab works by inhibiting blood vessel growth that tumors need to thrive, while irinotecan disrupts DNA replication in cancer cells. TAS-102, a combination of trifluridine and tipiracil hydrochloride, targets and blocks cancer cell division differently than other treatments. This multi-pronged strategy could potentially enhance effectiveness against colorectal cancer compared to standard treatments like FOLFOX or FOLFIRI, which primarily focus on just one mechanism. By attacking the cancer from different angles, this regimen might improve outcomes for patients who have limited options with existing therapies.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that a combination of three drugs—irinotecan, TAS-102, and bevacizumab—may help treat advanced colorectal cancer. This trial will evaluate this combination treatment, which studies have found can extend survival, especially for patients who haven't responded well to other treatments. Specifically, using TAS-102 with bevacizumab has been more effective than TAS-102 alone. Early results suggest that adding irinotecan enhances the treatment's effectiveness. This treatment appears effective and generally manageable for patients, causing relatively few side effects. ^{1 2 3 4 6}

Who Is on the Research Team?

Christos Fountzilas, MD, FACP

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal cancer that has spread or can't be surgically removed. Participants must have had prior treatment with certain chemotherapy drugs, have good physical function (ECOG 0-1), and meet specific blood count and organ function criteria. Pregnant women, those with recent major surgery, uncontrolled high blood pressure, serious heart conditions, or untreated brain metastases cannot join.

Inclusion Criteria

Absolute neutrophil count >= 1500/mm^3

Hemoglobin >= 9 g/dL

Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Exclusion Criteria

I do not have severe heart problems like unstable chest pain, heart failure needing treatment, or serious irregular heartbeat.

Proteinuria >= 2+, unless 24 hour urine collection demonstrates =< 1 g of protein OR spot protein: creatinine demonstrates a ratio of =< 1

I haven't had a different cancer, except for some skin or cervical types, in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive irinotecan IV over 90 minutes and bevacizumab IV over 30-90 minutes on days 1 and 15, and trifluridine and tipiracil hydrochloride orally twice daily on days 2-6 and 16-20. Cycles repeat every 28 days.

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 6 months for up to 2 years.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Irinotecan
• TAS-102

Trial Overview The study tests a combination of TAS-102 (a chemotherapy drug), irinotecan (another chemo drug), and bevacizumab (an immunotherapy agent) in patients who've previously been treated for metastatic or unresectable colorectal cancer. The goal is to see if this combo is more effective than traditional treatments.

How Is the Trial Designed?

Group I: Treatment (irinotecan, bevacizumab, TAS-102) Experimental Treatment 3 Interventions

Patients receive irinotecan IV over 90 minutes and bevacizumab IV over 10 minutes on days 1 and 15. Patients also receive trifluridine and tipiracil hydrochloride PO BID on days 2-6 and 16-20. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

National Comprehensive Cancer Network

Collaborator

Trials

121

Recruited

7,400+

Published Research Related to This Trial

In a study of 19 patients with metastatic colorectal cancer, the combination of biweekly TAS-102 and bevacizumab resulted in a median progression-free survival of 5.6 months and overall survival of 11.5 months, indicating its efficacy as a third-line treatment.

The treatment was generally safe, with only one patient experiencing severe neutropenia (grade 3 or more), suggesting that this combination therapy may effectively manage cancer while minimizing serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Multicenter Phase II Study of Biweekly TAS-102 and Bevacizumab for Metastatic Colorectal Cancer. Ishizaki, T., Mazaki, J., Enomoto, M., et al.[2021]

In a phase 1/2 trial involving 25 patients with heavily treated metastatic colorectal cancer, the combination of TAS-102 and bevacizumab showed promising activity, with a 16-week progression-free survival rate of 42.9%.

The treatment was found to have manageable safety, with the most common severe side effects being neutropenia and leucopenia, but no treatment-related deaths were reported, indicating that this combination could be a viable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open-label, single-arm, multicentre, phase 1/2 study. Kuboki, Y., Nishina, T., Shinozaki, E., et al.[2022]

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 of 35 patients with refractory metastatic colorectal cancer, the combination of trifluridine/tipiracil (TAS-102) and bevacizumab showed a disease control rate of 51.6% and a median overall survival of 9.3 months, indicating its efficacy in this challenging patient population.

The treatment was generally safe, with the most common severe side effects being neutropenia, asthenia, and nausea/vomiting, but importantly, there were no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting. Martínez-Lago, N., Chucla, TC., De Castro, BA., et al.[2022]

In a phase 3 study involving 856 patients with unresectable metastatic colorectal cancer, trifluridine-tipiracil plus bevacizumab showed similar progression-free survival compared to capecitabine plus bevacizumab, with median times of 9.4 months and 9.3 months respectively.

The safety profiles of the two treatments differed significantly, with trifluridine-tipiracil plus bevacizumab leading to higher rates of neutropenia and anemia, while capecitabine plus bevacizumab was associated with more cases of hand-foot syndrome, indicating that both treatments have distinct safety considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study. André, T., Falcone, A., Shparyk, Y., et al.[2023]

In a phase II study involving 153 patients with unresectable metastatic colorectal cancer, the combination of trifluridine/tipiracil plus bevacizumab (TT-B) demonstrated a median progression-free survival (PFS) of 9.2 months, which was longer than the 7.8 months observed with capecitabine plus bevacizumab (C-B).

Both treatment regimens were well tolerated, but TT-B was associated with a higher incidence of severe neutropenia (47% vs. 5% for C-B), while C-B led to more cases of severe hand-foot syndrome (12% vs. 0%) and diarrhea (8% vs. 1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study. Van Cutsem, E., Danielewicz, I., Saunders, MP., et al.[2022]

In a study of 57 patients with metastatic unresectable colorectal cancer treated with the combination of TAS-102 and bevacizumab, the incidence of nausea was 57.9% and vomiting was 17.5%, indicating that these side effects are common even after multiple treatment cycles.

Patients who had previously experienced nausea and vomiting from other treatments were found to be at a higher risk for similar side effects when treated with TAS-102 and bevacizumab, suggesting that prior treatment history is an important factor to consider in managing these symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emetogenicity and Risk Factors of Nausea and Vomiting in Patients With Metastatic Colorectal Cancer Receiving Trifluridine/Tipiracil and Bevacizumab Chemotherapy. Matsuoka, S., Fujii, H., Iihara, H., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39448860/

Phase II Study of Irinotecan, Trifluridine/tipiracil (TAS-102) ... Irinotecan, TAS-102 plus bevacizumab regimen preliminarily demonstrated promising efficacy with tolerable toxicity for mCRC patients as later-line treatment ...

2. nature.com nature.com/articles/s41416-024-02885-3

Phase II Study of Irinotecan, Trifluridine/tipiracil (TAS-102) ... Irinotecan, TAS-102 plus bevacizumab regimen preliminarily demonstrated promising efficacy with tolerable toxicity for mCRC patients as later‐line treatment.

3. 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.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39244627/

TAS-102, Irinotecan, and bevacizumab in pre-treated ... Abstract. Background: The efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.155

Phase II study of trifluridine/tipiracil (TAS-102) plus ... This study assessed the safety and efficacy of the trifluridine/tipiracil (TAS-102), irinotecan, and bevacizumab regimen in second-line settings ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04109924

Study Details | NCT04109924 | TAS-102, Irinotecan, and ... Giving TAS-102, irinotecan, and bevacizumab may work better in treating patients with colorectal cancer compared to traditional chemotherapy and bevacizumab.