TAS-102 + Nanoliposomal Irinotecan for Gastrointestinal Cancer

Not currently recruiting at 2 trial locations

Overseen By Olatunji B. Alese, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Emory University

Must not be taking: Irinotecan, Investigational therapy

Disqualifiers: Second malignancy, Heart failure, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Ongoing every 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and effectiveness of two chemotherapy drugs, TAS-102 (Trifluridine and Tipiracil Hydrochloride) and nanoliposomal irinotecan (Nal-IRI or Onivyde), for treating advanced gastrointestinal cancers that have spread or cannot be surgically removed. These drugs inhibit tumor cell growth and spread. The trial suits individuals with advanced gastrointestinal cancer, such as pancreatic or colorectal cancer, who have tried at least one unsuccessful treatment. Participants should have measurable disease and must not have previously received irinotecan. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's effects in people and assess its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial investigators to ensure they don't interfere with the study treatments.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get a clear answer.

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

Studies have shown that using TAS-102 with nanoliposomal irinotecan (Nal-IRI) is generally safe. Earlier research demonstrated that this combination effectively combats advanced colorectal cancer, helping to fight the disease without causing excessive side effects. Another study focused on nanoliposomal irinotecan and found it safe for patients with certain cancers, such as stomach and esophageal cancers, and in some cases, it even helped shrink tumors. Additionally, the FDA has approved nanoliposomal irinotecan for treating metastatic pancreatic cancer after other treatments, indicating its general safety and effectiveness. Overall, while risks exist, evidence suggests that this drug combination is reasonably safe for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nanoliposomal irinotecan and TAS-102 for gastrointestinal cancer because it introduces a novel approach to treatment. Unlike current options that often rely solely on traditional chemotherapy, this treatment utilizes nanotechnology to improve drug delivery. Nanoliposomal irinotecan is engineered to enhance absorption and prolong the circulation time of the drug in the body, potentially increasing its effectiveness against cancer cells. Additionally, TAS-102 combines trifluridine and tipiracil hydrochloride, offering a unique mechanism to disrupt cancer cell growth. This innovative combination aims to overcome resistance seen with existing therapies, offering hope for improved outcomes in patients.

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

Research has shown that the combination of TAS-102 and nanoliposomal irinotecan, which participants in this trial will receive, may help treat advanced gastrointestinal cancers. Studies have found that this drug pair can shrink tumors or halt their growth. For example, one study demonstrated that this combination was safe and effective for patients with advanced colorectal cancer. These drugs work together by using different methods to attack cancer cells, either by killing them or stopping their growth. This suggests that TAS-102 and nanoliposomal irinotecan could be a strong treatment option for hard-to-treat cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Olatunji Alese

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with advanced gastrointestinal cancers that are metastatic or can't be surgically removed. Participants must have tried at least one prior therapy, have measurable disease per RECIST 1.1, and adequate organ function. They should not have had irinotecan before (for certain phases), no recent severe heart issues or infections, and cannot be pregnant or breastfeeding.

Inclusion Criteria

Your platelet count is at least 100,000 per microliter within 14 days before starting treatment.

Your albumin levels in your blood are at least 3.0 grams per deciliter within 14 days before starting the treatment.

I am fully active or can carry out light work.

Exclusion Criteria

I have severe heart issues or uncontrolled blood pressure.

I have been cancer-free for 5 years, except for in-situ, basal, or squamous cell skin cancer.

I haven't had a severe heart attack, unstable chest pain, or stroke in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nanoliposomal irinotecan IV over 90 minutes on day 1 and TAS-102 orally twice daily on days 1-5. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Ongoing every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 8 or 12 weeks.

30 days initially, then every 8 or 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nanoliposomal Irinotecan
• Trifluridine and Tipiracil Hydrochloride

Trial Overview The trial is testing the combination of TAS-102 (trifluridine/tipiracil hydrochloride) and nanoliposomal irinotecan to find the best dose and see how well it works against various gastrointestinal cancers by stopping tumor growth.

How Is the Trial Designed?

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

Patients receive nanoliposomal irinotecan IV over 90 minutes on day 1 and combination of trifluridine/tipiracil hydrochloride combination agent TAS-102 PO BID on days 1-5. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Nanoliposomal Irinotecan is already approved in United States, European Union for the following indications:

Approved in United States as Onivyde for:

• Metastatic adenocarcinoma of the pancreas

Approved in European Union as Onivyde for:

• Metastatic adenocarcinoma of the pancreas

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Taiho Oncology, Inc.

Industry Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Ipsen

Industry Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

In a study of 67 patients with metastatic pancreatic cancer who had previously failed gemcitabine treatment, the combination of nanoliposomal irinotecan (nal-IRI) with 5-fluorouracil (5-FU) and leucovorin (LV) demonstrated a median overall survival of 7.9 months and a disease control rate of 38.8%.

The treatment was generally well-tolerated, with common side effects including anemia, nausea, and fatigue, indicating that nal-IRI + 5-FU/LV is a viable option for patients with advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoliposomal irinotecan with 5-fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy: A real-world experience. Yu, HY., Lee, CY., Lin, LG., et al.[2023]

In a phase II study involving 55 patients with metastatic colorectal cancer who had previously failed oxaliplatin treatment, the nanoliposomal irinotecan (PEP02) combined with leucovorin and 5-fluorouracil showed a 10.7% response rate, indicating its potential efficacy as a second-line treatment.

The safety profile of PEP02 was acceptable, with common grade 3-4 adverse events including diarrhea and neutropenia, but it demonstrated a lower incidence of these side effects compared to the standard irinotecan treatment (FOLFIRI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PEPCOL: a GERCOR randomized phase II study of nanoliposomal irinotecan PEP02 (MM-398) or irinotecan with leucovorin/5-fluorouracil as second-line therapy in metastatic colorectal cancer. Chibaudel, B., Maindrault-Gœbel, F., Bachet, JB., et al.[2021]

In a real-world study of 86 patients with metastatic pancreatic adenocarcinoma who received nal-IRI plus 5-FU/LV after gemcitabine therapy, the median overall survival was 9.4 months, indicating that this treatment is effective in this patient population.

The treatment was generally well-tolerated, with the most common severe side effects being neutropenia (37.2%) and nausea (10.5%), suggesting a manageable safety profile similar to findings from the NAPOLI-1 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group. Yoo, C., Im, HS., Kim, KP., et al.[2022]

Nanoliposomal irinotecan (nal-IRI) shows improved pharmacokinetics compared to nonliposomal irinotecan, with a longer half-life and higher plasma levels, which may enhance its efficacy in treating pancreatic cancer.

In a study of 353 patients, the optimal dosing of nal-IRI was determined to be 70 mg/m2 every two weeks, as it was associated with better efficacy and manageable safety profiles, particularly regarding neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer. Adiwijaya, BS., Kim, J., Lang, I., et al.[2022]

Nanoliposomal irinotecan (nal-IRI) improves the delivery and effectiveness of irinotecan in treating tumors, leading to prolonged exposure of its active metabolite, SN-38, while reducing systemic toxicity compared to traditional irinotecan.

The NAPOLI-1 Phase III trial demonstrated that nal-IRI, in combination with 5-fluorouracil and leucovorin, is effective for patients with metastatic pancreatic cancer after previous gemcitabine therapy, resulting in its FDA approval in 2015 as a new treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan. Ko, AH.[2018]

Liposomal irinotecan (Irinophore C™) demonstrated significant efficacy as a single agent in treating colorectal cancer, delaying tumor growth more effectively than the combination with 5-fluorouracil (5-FU).

The combination of IrC™ and 5-FU resulted in increased toxicity and altered pharmacokinetics of 5-FU, suggesting that while IrC™ is a promising treatment, its use with 5-FU may complicate treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of colorectal cancer using a combination of liposomal irinotecan (Irinophore C™) and 5-fluorouracil. Hare, JI., Neijzen, RW., Anantha, M., et al.[2021]

Liposomal irinotecan (nal-IRI) combined with 5-fluorouracil and leucovorin (5-FU/LV) has been shown to significantly improve median overall survival by approximately 2 months in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have previously been treated with gemcitabine, according to the phase III NAPOLI-1 trial.

This combination therapy not only enhances survival but also maintains a manageable safety profile and does not negatively impact the patients' quality of life, making nal-IRI a valuable treatment option for mPDAC patients in need of second-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma. Frampton, JE.[2021]

Irinophore C™, a lipid nanoparticle formulation of irinotecan, significantly reduced gastrointestinal toxicity, specifically diarrhea, in a rat model compared to unformulated irinotecan, which caused both early- and late-onset diarrhea in treated animals.

The nanoparticle formulation not only mitigated the toxic effects but also resulted in higher systemic concentrations of irinotecan, suggesting improved efficacy while reducing side effects when used alone or in combination with 5-fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinophore C™, a lipid nanoparticle formulation of irinotecan, abrogates the gastrointestinal effects of irinotecan in a rat model of clinical toxicities. Waterhouse, DN., Sutherland, BW., Santos, ND., et al.[2021]

Nanoliposomal irinotecan combined with 5-fluorouracil/folinic acid has been approved as the first second-line treatment for metastatic pancreatic cancer, showing significant improvements in progression-free survival (3.1 months vs. 1.5 months) and overall survival (6.2 months vs. 4.1 months) compared to 5-FU/folinic acid alone.

Patients receiving this combination therapy may experience more frequent adverse effects like neutropenia, fatigue, and diarrhea, necessitating careful monitoring and potential dose adjustments, especially for those with specific UGT1A1 gene variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the role of nanoliposomal irinotecan in the treatment of metastatic pancreatic cancer. Rahman, FAU., Ali, S., Saif, MW.[2020]

In a study of 58 patients with advanced pancreatic adenocarcinoma, the combination of nano-liposomal irinotecan (nal-IRI) and 5-fluorouracil/leucovorin (5-FU/LV) resulted in a median overall survival of 5.4 months, indicating a modest survival benefit as a second-line treatment.

The treatment was well-tolerated, with only 19% of patients experiencing grade 3/4 toxicities, suggesting that nal-IRI + 5-FU/LV has a favorable safety profile for patients who have progressed on prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of the combination of nano-liposomal irinotecan and 5-fluorouracil/leucovorin in advanced pancreatic adenocarcinoma: post-approval clinic experience. Kasi, A., McGinnis, T., Naik, G., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3580

OniLon: Phase II trial of trifluridine/tipiracil (TAS-102) and ... We demonstrated that the combination of TAS-102 and nal-IRI had an acceptable safety profile, and showed antitumor activity in patients with advanced CRC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03368963

NCT03368963 | TAS102 in Combination With NAL-IRI ... This phase I/II trial studies the best dose and how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) and nanoliposomal ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12310894/

A phase I study of liposomal Irinotecan (ONIVYDE®) in ... The favorable antitumor activity observed in our study may be attributed to shorter treatment intervals and the addition of TAS-102, which has ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)01211-4/fulltext

PD-4 A phase I trial of trifluridine/tipiracil in combination ... The combination of Nal-IRI with the more potent nucleoside analogue TAS-102 may result in a more effective systemic therapy regimen in gastrointestinal (GI) ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.660

Phase 1 study of nanoliposomal irinotecan in combination ... Nal-IRI + 5-FU/LV has been approved in patients with metastatic pancreatic cancer after gemcitabine-based therapy through the NAPOLI-1 study.