TAS-102 + Nanoliposomal Irinotecan for Gastrointestinal Cancer

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

64 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the best dose and how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) and nanoliposomal irinotecan work in treating patients with gastrointestinal cancers that have spread to other places in the body (metastatic) or cannot be removed by surgery. Drugs used in the chemotherapy, such as trifluridine/tipiracil hydrochloride combination agent TAS-102 and nanoliposomal irinotecan, 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.

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.

What data supports the idea that TAS-102 + Nanoliposomal Irinotecan for Gastrointestinal Cancer is an effective treatment?

The available research shows that Nanoliposomal Irinotecan, when combined with other drugs like 5-fluorouracil and leucovorin, is effective for treating metastatic pancreatic cancer, especially after other treatments have failed. In a major study, this combination helped patients live about two months longer on average compared to those who didn't receive it. This suggests that the drug can be a valuable option for patients who have not responded to initial treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug TAS-102 + Nanoliposomal Irinotecan for gastrointestinal cancer?

Nanoliposomal irinotecan (nal-IRI) has shown effectiveness in treating metastatic pancreatic cancer, especially when combined with other drugs like 5-fluorouracil, by improving survival rates in patients who did not respond to previous treatments. This suggests potential benefits for other gastrointestinal cancers, although direct evidence for this specific combination in gastrointestinal cancer is not provided. ^{1 2 3 4 5}

What safety data exists for TAS-102 + Nanoliposomal Irinotecan in gastrointestinal cancer treatment?

Nanoliposomal irinotecan (nal-IRI), also known as Onivyde, has been evaluated for safety in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in metastatic pancreatic cancer and colorectal cancer. Studies indicate that this combination is effective and generally safe, but it is associated with certain adverse effects such as neutropenia, fatigue, diarrhea, and nausea/vomiting. These side effects may require dose adjustments and growth factor support. The NAPOLI-1 study showed that nal-IRI with 5-FU/LV significantly improved survival compared to 5-FU/LV alone, but close monitoring is necessary due to the potential for adverse events. Additionally, genetic testing for UGT1A1 polymorphisms is recommended to adjust dosing appropriately. In a rat model, a lipid nanoparticle formulation of irinotecan, Irinophore C™, was shown to reduce gastrointestinal toxicity compared to unformulated irinotecan. Overall, nal-IRI has an acceptable safety profile, but careful management of side effects is crucial. ^{1 3 6 7 8}

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

Nanoliposomal Irinotecan, when used with other drugs like 5-fluorouracil, has been shown to be generally safe in humans, but it can cause side effects like neutropenia (low white blood cell count), fatigue, diarrhea, and nausea/vomiting. These side effects require careful monitoring and may need dose adjustments. In animal studies, a similar formulation reduced gastrointestinal side effects compared to traditional irinotecan. ^{1 3 6 7 8}

Is the drug Nanoliposomal Irinotecan, Trifluridine and Tipiracil Hydrochloride a promising treatment for gastrointestinal cancer?

Yes, the drug Nanoliposomal Irinotecan, Trifluridine and Tipiracil Hydrochloride is promising for gastrointestinal cancer. It has shown improved effectiveness and safety in treating cancers like pancreatic and colorectal cancer. The drug uses a special delivery system that helps it stay in the body longer and target tumors better, while reducing side effects compared to traditional treatments. ^{1 3 7 9 10}

What makes the drug TAS-102 + Nanoliposomal Irinotecan unique for gastrointestinal cancer?

This drug combines nanoliposomal irinotecan, which is a special form of irinotecan that stays in the body longer and causes less severe side effects, with TAS-102, a combination of trifluridine and tipiracil hydrochloride. The unique formulation allows for prolonged exposure to the active ingredient in tumors, potentially improving effectiveness while reducing common side effects like diarrhea. ^{1 3 7 9 10}

Research Team

Olatunji Alese

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

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

Treatment of colorectal cancer using a combination of liposomal irinotecan (Irinophore C™) and 5-fluorouracil. [2021]

2. England 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. [2022]

3. Netherlands 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. [2023]

4. China 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. [2022]

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

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

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

Update on the role of nanoliposomal irinotecan in the treatment of metastatic pancreatic cancer. [2020]

7. United States 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. [2021]

8. United States 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. [2021]

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

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

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

Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer. [2022]