Comparing two radiation therapies for pancreatic cancer before surgery

A Randomized, Phase II Clinical Trial of Preoperative Fractionated Radiation Therapy Versus Stereotactic Body Radiation Therapy for Resectable or Borderline Resectable, or Locally Advanced Type A Pancreatic Adenocarcinoma

This study is testing whether a new type of radiation therapy can work as well or better than the standard treatment for patients with pancreatic cancer before they have surgery.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 102 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical College of Wisconsin (other)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 1 site (Milwaukee, Wisconsin)
• Trial ID: NCT03704662 on ClinicalTrials.gov

What this trial studies

This clinical trial compares the effectiveness of Stereotactic Body Radiation Therapy (SBRT) with conventional preoperative fractionated radiation therapy combined with chemotherapy in patients with resectable or borderline resectable pancreatic adenocarcinoma. Patients will be randomized into two groups after undergoing a minimum of one cycle of induction chemotherapy, ensuring they have no evidence of distant metastatic disease. The study aims to determine if SBRT can achieve similar or better outcomes in terms of nodal downstaging compared to conventional methods. Approximately 102 patients will be enrolled to assess the safety and efficacy of these treatment modalities.

Who should consider this trial

Good fit: Ideal candidates include individuals with pathologically confirmed resectable, borderline resectable, or locally advanced type A pancreatic adenocarcinoma without biopsy-proven metastatic disease.

Not a fit: Patients with confirmed metastatic pancreatic cancer will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective preoperative treatment option for patients with pancreatic cancer, potentially improving surgical outcomes.

How similar studies have performed: While there is limited direct comparison data, existing literature suggests that SBRT is safe and convenient, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Pathologically confirmed (histologic or cytological), resectable, borderline resectable, or locally advanced type A adenocarcinoma of the pancreas; patients must have resectable, borderline resectable, or locally advanced type A disease, based on institutional standardized criteria and tumor board review.
2. Patients with and without regional adenopathy are eligible.
3. Patients are eligible with either no evidence of distant metastatic disease, or "equivocal" evidence of distant metastatic disease, as judged by multidisciplinary review. This "equivocal" definition can include small lung or liver lesions that are not able to be radiographically characterized otherwise. Any biopsy-proven metastatic disease will make the patient ineligible for study participation.
4. History/physical examination, including collection of weight and vital signs, within 45 days prior to start of treatment.
5. Diagnostic abdominal/pelvic CT with IV contrast or abdominopelvic MRI scan with perfusion and diffusion-weighted sequences within 45 days prior to study entry.
6. Chest CT scan or X-ray within 30 days prior to study entry.
7. Radiation treatment planning abdominal CT. A recommended abdominal MRI will be done as a simulation (SIM) with interpretation. The CT SIM will not be done with interpretation. Positron emission tomography (PET) scan and MRI are both optional but encouraged. Ability to undergo abdominal MR scans for staging and radiation planning and follow-up is optional but encouraged.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 14 days of randomization.
9. Age ≥ 18.
10. Heme Onc (Chem 24) and cancer antigen (CA) 19-9/carcinoembryonic antigen (CEA) within 45 days prior to treatment, as follows:

    * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
    * Platelets ≥100,000 cells/mm3 (see section 4)
    * Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
    * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 4 x upper limit of normal
    * Total bilirubin \< 1.5 x upper normal mg/dL
    * Alkaline phosphatase \< 4 x upper limit of normal
11. Not on hemodialysis.
12. Negative serum pregnancy test (if applicable).
13. Ability to swallow oral medications.
14. Patients must have had at least one cycle of systemic chemotherapy without evidence of distant progression.
15. Patient must provide study-specific informed consent prior to study entry.
16. Women of childbearing potential and male participants who are sexually active must practice adequate contraception.

Exclusion Criteria:

1. Distant metastatic disease.
2. Prior invasive malignancy (except nonmelanomatous skin cancer), unless disease free for a minimum of three years (for example, carcinoma in situ of the breast, oral cavity or cervix are all permissible).
3. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
4. Any major surgery within 28 days prior to study entry (for example, insertion of a vascular access device or biliary stent, exploratory laparotomy and/or laparoscopy are not considered major surgery; biliary or gastric bypass is considered major surgery).
5. Severe, active comorbidity, defined as follows:

   * Unstable angina and/or congestive heart failure requiring hospitalization within the last six months.
   * Transmural myocardial infarction within three months prior to study entry.
   * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
   * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration.
   * Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function.
   * Any unresolved bowel or bile duct obstruction.
   * Major resection of the stomach or small bowel that could affect the absorption of capecitabine.
   * Acquired immune deficiency syndrome (AIDS), based upon current Center for Disease Control (CDC) definition. Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because patients receiving antiretroviral therapy may experience possible pharmacokinetic interactions with capecitabine.
   * Absence of any significant medical comorbidity which would preclude the consideration of major pancreatic surgery.
6. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during the course of the study and for women three months after study therapy is completed and for men six months after study therapy is completed. This exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
7. Women who are lactating at the time of registration and who plan to be lactating through three months after study therapy is completed.
8. Prior allergic reaction to capecitabine or gemcitabine.
9. Participation in another interventional clinical treatment trial while on study (observational trials are permitted).
10. Patients taking nonprotocol-specified chemotherapy agents or immune modulating agents for other medical conditions are not permitted to participate in this trial. Any medication questions should be reviewed by the PI.

Where this trial is running

Milwaukee, Wisconsin

• Froedtert Hospital & Medical College of Wisconsin — Milwaukee, Wisconsin, United States (RECRUITING)

Study contacts

• Principal investigator: William Hall, MD — Medical College of Wisconsin
• Study coordinator: Medical College of Wisconsin Cancer Center Clinical Trials Office

Conditions: Pancreatic Cancer, resectable pancreatic adenocarcinoma, borderline resectable pancreatic adenocarcinoma, Stereotactic Body Radiation Therapy, Preoperative Fractionated Radiation Therapy