A Study of NALIRIFOX in Combination With Radiation Therapy in People With Pancreatic Ductal Adenocarcinoma (PDAC)

Total Neoadjuvant NALIRIFOX Plus Ablative Dose Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

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

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: NALIRIFOX; Combination product: AD-XRT and Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eileen O'Reilly, MD; Phone Number: 646-888-4182
• Study Contact Backup: Name: Alice Wei, MD; Phone Number: 212-639-5643; Email: weia@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Alice Wei, MD; Phone Number: 212-639-5643
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Alice Wei, MD; Phone Number: 212-639-5643
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Alice Wei, MD; Phone Number: 212-639-5643
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities)
      • Contact: Alice Wei, MD; Phone Number: 212-639-5643
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Alice Wei, MD; Phone Number: 212-639-5643
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Eileen O'Reilly, MD; Phone Number: 646-888-4182
      • Contact: Alice Wei, MD; Phone Number: 212-639-5643
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Alice Wei, MD; Phone Number: 212-639-5643

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject has been informed about the nature of the study, has agreed to participate in the study, and has signed the informed consent form before participation in any study-related activities.

2. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy.

   Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, DCIS, stage I prostate cancer, and basal cell or squamous cell carcinoma of the skin.

3. A multidisciplinary discussion has been undertaken/planned which can include (a) discussion with medical/surgery oncology, (b) Hepatopancreaticobiliary Disease Management Team conference presentation, (c) direct consultation, with confirmation on consensus plan for TNT strategy and potential for future surgery. This plan needs to be documented in the medical record prior to initiation of treatment.

4. Male or nonpregnant and nonlactating female aged ≥18 years.

   1. Women of child-bearing potential (i.e., fertile, following menarche, and until becoming postmenopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) must test negative for pregnancy at the time of screening on the basis of a urine or serum pregnancy test. Postmenopausal women are defined as those who have had an absence of menstruation for at least 2 years. If necessary, follicle-stimulating hormone results >50 IU/L at screening are confirmatory in the absence of a clear postmenopausal history.
   2. Female subjects of reproductive potential must agree to use two effective methods of birth control during the study and for 9 months after the last dose of study medication.
   3. Male subjects must agree to use condoms during the study and for 4 months after the last dose of study medication'

Disease-specific inclusion criteria:

1. Histologically or cytologically confirmed PDAC that has not been previously treated.
2. Radiographically BR or LA PDAC in accordance with the NCCN 2.2021 definition, without evidence of distant metastases by CT.
3. Inoperable status after surgical exploration due to presence of locally advanced, unresectable disease without metastases, in patients who have recovered from surgery, is allowed.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. Hematological, biochemical, and organ function inclusion criteria:

   1. Absolute neutrophil count (ANC) ≥1500/mm^3 without the use of hemopoietic growth factors within 7 days before treatment
   2. Platelet count ≥100,000/mm^3 .
   3. International normalized ratio (INR) <1.5 unless the patient is receiving anticoagulation therapy, in which case a therapeutic INR is acceptable. Anticoagulation therapy with low-molecularweight heparin or warfarin, whether medically indicated, is permitted.
   4. Adequate renal function, as evidenced by serum/plasma creatinine level <1.6 mg/dL

Exclusion Criteria:

1. Presence of metastatic pancreatic cancer (M1 disease)
2. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, and participate in the study or who is likely to interfere with the interpretation of the results.
3. Unwilling or unable to comply with study procedures and/or study visits.
4. Medical co-morbidities, that preclude major abdominal surgery
5. Histologic diagnosis other than adenocarcinoma; however, adenosquamous variants are acceptable.
6. Receipt of chemotherapy, prior abdominal radiotherapy, and/or definitive resection for pancreatic cancer.
7. Grade >2 neuropathy.
8. Pregnant and/or nursing.
9. Uncontrolled active infection, which would preclude with the exception of resolving cholangitis which in the investigator opinion would render the treatment hazardous.
10. Known hypersensitivity to any of the components of the chemotherapeutic agents

11. Receipt of concurrent investigational therapy or within 30 days of protocol initiation.

    Additional criterion for the immunoPET imaging sub-study (n=20)

12. Previous anaphylactic reaction to human, humanized or chimeric antibody.
13. Refusal or inability to tolerate the scanning procedure (e.g. due to claustrophobia).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NALIRIFOX + AD-XRT and capecitabine; 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.

Drug: NALIRIFOX; Patients will receive NALIRIFOX for a total of 4 months. NALIRIFOX will be administered on days 1 and 15 of a 4-week cycle for 4 cycles until completion of therapy, intolerable toxicity, or until the development of criteria for removal from the study. Liposomal irinotecan: 50 mg/m2 IV over the course of 90 minutes (±10 minutes) on days 1 and 15 of every 4-week cycle. Oxaliplatin: 60 mg/m2 IV over the course of 120 minutes (±10 minutes) on days 1 and 15 of every 4-week cycle. Leucovorin: 400 mg/m2 IV over the course of 30 minutes (±5 minutes) on days 1 and 15 of every 4-week cycle. 5-FU: 2400 mg/m2 IV over the course of 46 hours (±60 minutes) on days 1 and 15 of every 4-week cycle; Combination product: AD-XRT and Capecitabine; The interval between completion of induction chemotherapy and initiation of AD-XRT will be 2-6 weeks. The patient will be concurrently treated with capecitabine (1000-1500 mg flat BID PO Monday to Friday) with radiation, as per standard dosing regimens at MSK.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event-free survival (EFS)	events defined as: 1) progression [local or systemic progression, per RECIST], 2) recurrence [recurrent disease following resection], or 3) death due to any cause	up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS) rate	defined as the time from enrollment to death from any cause. Patients alive are censored at the date of last contact	up to 5 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Ipsen; Pancreatic Cancer Research Fund
• Investigators: Principal Investigator: Alice Wei, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 1, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: NALIRIFOX; Ablative Dose Radiation; 23-027
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: 23-027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No