Combining NALIRIFOX and Radiation Therapy for Pancreatic Cancer Treatment

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

This study is testing if a combination of a new chemotherapy drug called NALIRIFOX, radiation therapy, and a standard chemotherapy drug can help people with locally advanced pancreatic cancer before they have surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT05851924 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of the chemotherapy regimen NALIRIFOX combined with ablative dose radiation therapy (AD-XRT) and the standard chemotherapy drug capecitabine for patients with locally advanced or borderline resectable pancreatic ductal adenocarcinoma (PDAC) prior to surgery. The approach, known as total neoadjuvant therapy (TNT), aims to evaluate both the efficacy and the side effects of this treatment sequence. Additionally, the study will assess the impact of the treatment on participants' quality of life through questionnaires. The goal is to determine if this combination can improve outcomes for patients facing this challenging cancer.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with locally advanced or borderline resectable pancreatic ductal adenocarcinoma who are eligible for total neoadjuvant therapy.

Not a fit: Patients with advanced pancreatic cancer that is not resectable or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could enhance survival rates and quality of life for patients with pancreatic ductal adenocarcinoma.

How similar studies have performed: Other studies have shown promise with similar neoadjuvant treatment approaches for pancreatic cancer, indicating potential for success.

Eligibility criteria

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).

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (Recruiting)

Study contacts

• Principal investigator: Alice Wei, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Alice Wei, MD

Conditions Pancreatic Ductal Adenocarcinoma; NALIRIFOX; Ablative Dose Radiation; 23-027