NALIRIFOX + Radiation for Pancreatic Cancer

Recruiting at 6 trial locations

Overseen By Eileen M O'Reilly, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Metastatic cancer, Major surgery, Neuropathy, others

Stay on Your Current Meds You can continue your current medications while participating

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: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment plan for individuals with pancreatic ductal adenocarcinoma that hasn't spread. It combines a chemotherapy regimen called NALIRIFOX with ablative dose radiation therapy (AD-XRT) and another chemotherapy drug, capecitabine, before surgery to assess effectiveness and side effects. Researchers are also examining how these treatments might impact participants' quality of life. Individuals with locally advanced or borderline resectable pancreatic cancer, who have not received prior treatment, may qualify for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does allow for anticoagulation therapy (blood thinners) if medically indicated, so it might depend on the specific medications you are taking. It's best to discuss this with the trial team.

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

Research has shown that the treatments in this trial have promising safety records from previous studies.

For NALIRIFOX, studies indicate that this drug combination is generally well-tolerated. Some patients experienced side effects like nausea and tiredness, but these were often manageable. Importantly, past testing has demonstrated potential benefits with a safety profile that supports its use.

Ablative dose radiation therapy (AD-XRT) has also been studied for safety. Research shows that while some patients might experience side effects like stomach issues, severe reactions are rare. The treatment effectively controls local tumors without significantly increasing severe side effects.

Capecitabine, another drug in the trial, has a well-known safety record. It is generally well-tolerated, with some patients experiencing side effects like redness and swelling in the hands and feet, and stomach issues. However, these side effects are usually mild to moderate.

Overall, previous research has shown that the treatments in this study can be safe and tolerable. This suggests that participants might expect similar safety outcomes, although individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NALIRIFOX combined with AD-XRT and capecitabine for pancreatic cancer because it offers a unique multi-modal approach. Unlike traditional treatments like FOLFIRINOX or gemcitabine with nab-paclitaxel, which primarily rely on chemotherapy alone, this treatment pairs chemotherapy with targeted radiation (AD-XRT). This combination aims to shrink tumors effectively, potentially making them resectable and improving surgical outcomes. Additionally, the use of neoadjuvant chemotherapy followed by a precise radiation schedule allows for a tailored treatment plan based on individual response, which could lead to better long-term results for patients.

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

In this trial, participants will receive a combination of treatments. Research has shown that NALIRIFOX, a mix of chemotherapy drugs, has potential in treating pancreatic cancer. Studies have found it can help patients live longer and shrink tumors, making surgery an option for more people. Ablative dose radiation therapy (AD-XRT), also included in this trial, has been linked to better survival rates and helps control tumor growth. Additionally, Capecitabine, a chemotherapy pill used in this trial, has shown positive results when combined with radiation, increasing survival chances. Together, these treatments could offer a strong approach to fighting pancreatic cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Alice Wei, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with locally advanced or borderline resectable pancreatic ductal adenocarcinoma (PDAC) that hasn't been treated before. They must be in good health, have no history of certain cancers within the last 5 years except some specific types, and women must not be pregnant and agree to birth control measures. Men must also agree to use contraception.

Inclusion Criteria

I was diagnosed and treated for certain early-stage cancers or skin cancer within the last 5 years.

My white blood cell count is healthy without needing medication to boost it.

I agree to use two forms of birth control during and for 9 months after the study.

Exclusion Criteria

I am willing and able to follow the study's procedures and attend all visits.

Known hypersensitivity to any of the components of the chemotherapeutic agents.

I do not have any infections that could make treatment dangerous, except for possibly resolving cholangitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive NALIRIFOX chemotherapy for 4 months with CT scans at 8 and 16 weeks to assess treatment response

16 weeks

2 visits (in-person) for CT scans

Radiation Therapy

Participants undergo ablative dose radiation therapy (AD-XRT) for 15 to 25 fractions over 3 to 5 weeks

3-5 weeks

Surgery

Participants whose disease is deemed resectable will be recommended for surgical intervention

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• AD-XRT
• Capecitabine
• NALIRIFOX

Trial Overview

The study tests a chemotherapy regimen called NALIRIFOX combined with ablative dose radiation therapy (AD-XRT) and capecitabine before surgery in patients with PDAC. It aims to assess if this total neoadjuvant therapy (TNT) sequence is effective and tolerable, while also monitoring participants' quality of life through questionnaires.

How Is the Trial Designed?

Group I: NALIRIFOX + AD-XRT and capecitabine Experimental Treatment 2 Interventions

Patients will receive neoadjuvant chemotherapy for 4 months. Patients will undergo a CT scan at 8 weeks and 16 weeks after the start of neoadjuvant chemotherapy to assess treatment response. Patients without disease progression will then undergo AD-XRT for 15 to 25 fractions (3 to 5 weeks). Patient's whose disease is deemed resectable based on their re-evaluating imaging, will be recommended surgical intervention with consideration for laparotomy or laparoscopy if deemed appropriate at multidiscplinary cancer conference review.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Pancreatic Cancer Research Fund

Collaborator

Trials

2

Recruited

3,600+

Published Research Related to This Trial

In a study of 424 patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant (m)FOLFIRINOX, adding radiotherapy (RT) did not improve overall survival compared to those who did not receive RT, with median survival times of 26.2 months versus 32.8 months, respectively.

While RT was linked to a lower rate of surgical resection (55.3% vs 72.7%) and did not affect overall survival, it did result in more favorable outcomes for those who underwent surgery, such as a higher rate of node-negative disease and a greater pathologic response, suggesting that RT may have some benefits in specific contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Radiotherapy After (m)FOLFIRINOX for Borderline Resectable Pancreatic Adenocarcinoma: A TAPS Consortium Study. Janssen, QP., van Dam, JL., Prakash, LR., et al.[2023]

In a study of 25 patients with locally advanced unresectable pancreatic cancer (LAPC), those who received FOLFIRINOX followed by radiotherapy had a median overall survival of 15.4 months, indicating a potential benefit from this treatment approach.

Despite severe toxicity associated with FOLFIRINOX, 77% of patients completed all treatment cycles, and 14% were able to undergo radical resection after therapy, suggesting that this regimen can be tolerated and may lead to significant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX and radiotherapy for locally advanced pancreatic cancer: A cohort study. Suker, M., Nuyttens, JJ., Groot Koerkamp, B., et al.[2021]

In a phase II trial involving 21 patients with untreated advanced pancreatic cancer, the combination treatment of trimetrexate, leucovorin, and 5-fluorouracil (NFL) was found to be well-tolerated, with serious toxicities occurring in a minority of patients (23.8% experienced Grade 3 diarrhea).

The treatment resulted in a median survival of 6.8 months and a 1-year survival rate of 19%, which is comparable to other available treatment options for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer. Garcia, AA., Leichman, L., Baranda, J., et al.[2018]

The study established that the maximum tolerated dose of capecitabine and oxaliplatin (CAPOX) combined with radiation therapy (RT) is safe for patients with locally advanced pancreatic adenocarcinoma, with acceptable toxicity observed at the highest dose level tested.

While CAPOX-RT showed a response rate of 38%, it did not improve overall survival compared to gemcitabine-based therapy (GEM-RT) or 5-fluorouracil (5FU-RT), indicating that while CAPOX-RT is tolerable, it may not be more effective than existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective phase I study of capecitabine and oxaliplatin concurrent with radiation therapy for the treatment of locally advanced pancreatic adenocarcinoma, and retrospective comparison to concurrent 5-fluorouracil/radiation and gemcitabine/radiation. Hazard, L., Jones, K., Shaban, A., et al.[2022]

The maximum tolerated dose of irinotecan combined with radiotherapy for patients with locally advanced pancreatic adenocarcinoma was found to be 18 mg/m² per day, with significant gastrointestinal side effects such as nausea, vomiting, and diarrhea.

Despite the primary focus on safety, the study reported a median survival time of 12.6 months, suggesting that this treatment regimen may offer promising outcomes for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of daily irinotecan as a radiation sensitizer for locally advanced pancreatic cancer. de la Fouchardière, C., Négrier, S., Labrosse, H., et al.[2018]

A series of clinical trials initiated by the Gastrointestinal Tumor Study Group in the 1970s explored the effectiveness of radiation therapy combined with chemotherapy for treating pancreatic, rectal, and gastric adenocarcinomas, which were previously thought to be resistant to radiation.

The trials included various treatment protocols, such as comparing high-dose radiation with chemotherapy to lower doses, and consistently used 5-fluorouracil as a chemotherapeutic agent, indicating a systematic approach to improving outcomes for patients with locally unresectable tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An organized multi-institutional interdisciplinary evaluation of role of radiation therapy alone or combined with chemotherapy in treatment of adenocarcinoma of the gastrointestinal tract. Douglass, HO., Stablein, DM., Thomas, PR.[2007]

In a study of 35 patients with locally advanced unresectable pancreatic cancer, those who received adjuvant chemotherapy with doxifluridine (5'-DFUR) after radiotherapy showed significantly improved survival rates compared to those who received radiotherapy alone, with 1-year survival rates of 50% versus 29%.

The addition of 5'-DFUR not only prolonged survival but also delayed tumor marker elevation and improved local control of the disease, indicating its potential as an effective treatment strategy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefits of adjuvant chemotherapy with oral doxifluridine (5'-DFUR) following radiotherapy in patients with unresectable pancreatic cancer. Tsuruta, K., Okamoto, A., Egawa, N., et al.[2019]

The combination of doxifluridine (5-DFUR) and radiotherapy improved the chances of surgical resection in patients with locally unresectable pancreatic cancer, achieving a 16% resectability rate in a study of 32 patients.

The median survival time for all patients was 9 months, with a 1-year survival rate of 31%, indicating that this treatment regimen is both feasible and potentially effective, with no severe toxic events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. Bajetta, E., Di Bartolomeo, M., Stani, SC., et al.[2019]

Combination treatment with chemoradiation is more effective than chemotherapy or radiotherapy alone for pancreatic cancer, improving local control and median overall survival after surgery.

Adjuvant chemoradiation is superior to surgery alone, but many patients cannot receive it due to recovery issues, leading to a preference for primary chemoradiation, which shows promising results with drugs like 5-fluorouracil and ongoing studies with newer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant concomitant chemotherapy in pancreatic cancer]. Turci, D., Cariello, A., De Giorgi, U., et al.[2022]

In a phase I-II trial involving 39 patients with locally advanced pancreatic or biliary tract cancer, the combination of capecitabine and oxaliplatin with radiotherapy was found to be well tolerated, with maximum tolerated doses established at 30 mg/m² for oxaliplatin and 675 mg/m² for capecitabine.

The treatment resulted in a 21% partial response rate, with a 2-year survival rate of 28% and a local tumor control rate of 72%, indicating its potential efficacy in managing these difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre phase I-II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable pancreatic and biliary tract cancer: The CORGI-U study. Gunnlaugsson, A., Anderson, H., Lind, P., et al.[2018]

In a phase I/II trial involving 24 patients with borderline resectable and locally advanced unresectable pancreatic cancer, the combination of 5FU, oxaliplatin, and radiation was found to be reasonably well tolerated, with the highest dose of oxaliplatin (60 mg/m2) being recommended for further studies.

Despite the treatment, only 8.3% of patients achieved curative resection, and the median overall survival was 11.4 months, indicating that while the regimen is manageable, it may not significantly improve resectability or survival compared to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can we downstage locally advanced pancreatic cancer to resectable? A phase I/II study of induction oxaliplatin and 5-FU chemoradiation. Amodeo, S., Masi, A., Melis, M., et al.[2023]

Neoadjuvant chemoradiation, particularly with fluorouracil (5-FU) plus radiation, is now the preferred treatment for stage II/III rectal cancer, showing lower local relapse rates and better safety compared to postoperative treatments.

Capecitabine (Xeloda) plus radiation has been found to be as effective as 5-FU plus radiation, making it a viable alternative, while combinations with oxaliplatin or irinotecan show promise for improved outcomes and warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation for rectal cancer: is more better? Patel, A., Puthillath, A., Yang, G., et al.[2018]

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