Neoadjuvant chemotherapy for resectable pancreatic cancer

A Single-Arm Phase II Clinical Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma

This study is testing a combination of three chemotherapy drugs to see if it helps people with resectable pancreatic cancer get better before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Emory University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Atlanta, Georgia)
• Trial ID: NCT06423326 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of a combination of gemcitabine, cisplatin, and nab-paclitaxel as neoadjuvant treatment for patients with resectable or borderline resectable pancreatic cancer. The study aims to determine the major pathological response rate, feasibility, and safety of this treatment regimen before surgical intervention. Patients will receive the chemotherapy drugs biweekly for up to four cycles, followed by surgical resection if there is a favorable response. Additionally, the trial will assess the impact of this treatment on the immune response against the tumor.

Who should consider this trial

Good fit: Ideal candidates are individuals with histologically confirmed resectable or borderline resectable pancreatic ductal adenocarcinoma.

Not a fit: Patients with unresectable pancreatic cancer or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve overall survival rates for patients with pancreatic cancer.

How similar studies have performed: Other studies have shown promising results with neoadjuvant chemotherapy approaches for pancreatic cancer, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Histologically or cytologically confirmed - resectable and borderline resectable pancreatic ductal adenocarcinoma

  * Resectability will be defined as per National Comprehensive Cancer Network (NCCN) guidelines using cross-sectional imaging (contrast-enhanced computed tomography or magnetic resonance imaging scans of the abdomen, and pelvis)
  * Decisions about resectability status will be made in consensus at multidisciplinary meetings/discussions

Resectable disease will be defined as:

* No interface of the tumor with celiac artery, common hepatic artery (CHA), or superior mesenteric arteries (SMA) (and, if present, variants)
* Less than 180° interface between tumor and vessel wall of the portal or superior mesenteric veins (SMV) without vein contour irregularity
* For tumors of the body and tail of the pancreas, interface with the splenic artery and splenic vein of any degree will be considered resectable disease

Borderline resectable disease will be defined as:

* To include at least one of the following:

  * Tumor abutment \< 180° of the superior mesenteric artery or celiac axis
  * Solid tumor contact with CHA without extension to celiac artery (CA) or hepatic artery bifurcation allowing for safe and complete resection and reconstruction
  * Solid tumor contact with variant arterial anatomy (ex: accessory right hepatic artery, replaced right hepatic artery, replaced CHA, and the origin of replaced or accessory artery)
  * Tumor induced narrowing of SMV, portal vein (PV) or SMV-PV of \> 180˚ of the diameter of the vessel
  * Short segment occlusion of the SMV, PV or SMV-PV with a suitable PV above and SMV below, for reconstruction
  * Solid tumor contact with inferior vena cava
  * Biopsy proven N1 disease (regional lymph nodes involved) from pre-referral biopsy or endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA)

    * No distant extrapancreatic disease (M0)
    * Adults \> 18 years of age
    * Able to give informed consent
    * Able to adhere to study visit schedule and other protocol requirements
    * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
    * Absolute neutrophil count (ANC) ≥ 1,500 cells/ul
    * Platelet count ≥ 100,000 cells/ul
    * Hemoglobin ≥ 9 g/dL
    * Serum total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
    * Albumin ≥ 3 g/dl
    * Creatinine ≤ 1.5 x ULN
    * Male, or a non-pregnant and non-lactating female
    * Women of child-bearing potential - defined as a sexually mature woman who has not undergone hysterectomy - the surgical removal of the uterus or bilateral oophorectomy - the surgical removal of both ovaries or has not been naturally postmenopausal for at least 24 consecutive months, i.e., has had menses at any time during the preceding 24 consecutive months, must commit to true abstinence from heterosexual contact, or agree to use, and be able to comply with, effective contraception without interruption for 28 days prior to starting gemcitabine/cisplatin/nab- paclitaxel (including dose interruptions) until treatment with gemcitabine/cisplatin/nab-paclitaxel is complete
    * Male subjects must practice true abstinence or agree to use a condom during sexual contact with a female of childbearing potential or a pregnant female while on treatment (including during dose interruptions) with gemcitabine/cisplatin/nab-paclitaxel and for 6 months following gemcitabine/cisplatin/nab- paclitaxel discontinuation, even if he has undergone a successful vasectomy

Exclusion Criteria:

* Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)"
* Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, symptomatic congestive heart failure, uncontrolled diabetes, serious active, uncontrolled infection after inadequate biliary drainage if tumor obstructing bile duct, or psychiatric illness/social situations
* Pregnancy (positive pregnancy test) or lactation
* Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (radiosurgery \[RS\]; Gamma Knife, linear accelerator \[LINAC\], or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded
* Previous (within the past 5 years) or concurrent presence of other untreated cancer, except nonmelanoma skin cancer and in situ carcinomas
* History of allergy or hypersensitivity to any of the study drugs
* Current abuse of alcohol or illicit drugs
* Inability or unwillingness to sign the informed consent form

Where this trial is running

Atlanta, Georgia

• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States (Recruiting)

Study contacts

• Principal investigator: Hussein M Hamad, MD, MPH — Emory University Hospital/Winship Cancer Institute
• Study coordinator: Hussein M. Hamad, MD, MPH

Conditions Borderline Resectable Pancreatic Ductal Adenocarcinoma; Resectable Pancreatic Adenocarcinoma; Stage I Pancreatic Cancer AJCC v8; Stage II Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8