NALIRIFOX + Radiation for Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Alice Wei, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Metastatic cancer, Major surgery, Neuropathy, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to find out whether using the chemotherapy regimen NALIRIFOX in combination with ablative dose radiation therapy (AD-XRT) and the standard chemotherapy drug capecitabine is an effective treatment approach for people with locally advanced or borderline resectable pancreatic ductal adenocarcinoma (PDAC) before surgery. This type of treatment approach is called total neoadjuvant therapy (TNT). The researchers will also look at whether the sequence of the treatment approach (NALIRIFOX + ADXRT and capecitabine followed by surgery, when it is possible) is effective and causes few or mild side effects in participants. An important purpose of the study is to see how the study treatment (NALIRIFOX + AD-XRT and capecitabine) affects participants' quality of life. The researchers will measure quality of life by having participants fill out questionnaires

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.

What data supports the effectiveness of the treatment NALIRIFOX + Radiation for Pancreatic Cancer?

Research shows that combining capecitabine and oxaliplatin with radiation therapy can be effective for treating locally advanced pancreatic cancer, as seen in studies like the CORGI-U trial. Additionally, using chemoradiation (a combination of chemotherapy and radiation) with drugs like 5-fluorouracil and oxaliplatin has shown potential in controlling local disease and possibly making tumors resectable (able to be surgically removed). ^{1 2 3 4 5}

Is the combination of NALIRIFOX and radiation therapy safe for treating pancreatic cancer?

Studies have shown that combinations of drugs like capecitabine, oxaliplatin, irinotecan, and fluorouracil with radiation therapy have been tested for safety in treating pancreatic cancer. These studies aimed to find the maximum tolerated doses and reported favorable safety profiles, but further research is needed to confirm these findings in larger trials. ^{1 2 6 7 8}

How does the NALIRIFOX + Radiation treatment for pancreatic cancer differ from other treatments?

The NALIRIFOX + Radiation treatment is unique because it combines multiple chemotherapy drugs, including liposomal irinotecan and oxaliplatin, with high-dose radiation therapy, aiming to enhance the effectiveness of treatment by targeting cancer cells more aggressively than traditional methods like 5-fluorouracil with radiation. ^{1 9 10 11 12}

Research Team

Alice Wei, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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 am an adult over 18 and not pregnant or breastfeeding.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• AD-XRT (Radiation)
• Capecitabine (Chemotherapy)
• NALIRIFOX (Chemotherapy)

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.

Participant Groups

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+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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 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]

References

1. United States 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. [2022]

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

Neoadjuvant Radiotherapy After (m)FOLFIRINOX for Borderline Resectable Pancreatic Adenocarcinoma: A TAPS Consortium Study. [2023]

3. United States 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. [2007]

4. Ireland 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. [2018]

5. China 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. [2023]

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

FOLFIRINOX and radiotherapy for locally advanced pancreatic cancer: A cohort study. [2021]

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

Neoadjuvant chemoradiation for rectal cancer: is more better? [2018]

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

Phase I study of daily irinotecan as a radiation sensitizer for locally advanced pancreatic cancer. [2018]

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

Survival benefits of adjuvant chemotherapy with oral doxifluridine (5'-DFUR) following radiotherapy in patients with unresectable pancreatic cancer. [2019]

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

Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. [2019]

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

[Adjuvant concomitant chemotherapy in pancreatic cancer]. [2022]

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

Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer. [2018]