This phase II clinical trial studies how well combination chemotherapy and stereotactic body radiation therapy before surgery followed by combination chemotherapy works in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving paclitaxel albumin-stabilized nanoparticle formulation, gemcitabine hydrochloride, and stereotactic body radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed, and giving paclitaxel albumin-stabilized nanoparticle formulation and gemcitabine hydrochloride after surgery may kill any remaining tumor cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02723331.
PRIMARY OBJECTIVES:
I. To estimate the microscopically margin-negative (R0) resection rate in patients with resectable pancreatic ductal adenocarcinoma (PDAC) as well as those with borderline resectable PDAC independently in response to neoadjuvant sequential therapy of combination gemcitabine and nab-paclitaxel followed by stereotactic body radiation therapy (SBRT).
SECONDARY OBJECTIVES:
I. To assess safety and feasibility of perioperative therapy with neoadjuvant gemcitabine and nab-paclitaxel (nab-paclitaxel) (paclitaxel albumin-stabilized nanoparticle formulation) chemotherapy followed by stereotactic radiotherapy before surgery in addition to adjuvant gemcitabine and nab-paclitaxel.
II. Estimation of objective response rate in response to neoadjuvant therapy.
III. Estimation of overall survival: overall survival, defined as the time from study treatment initiation until death from any cause.
IV. Estimation of progression-free survival: progression-free survival (PFS), defined as the time from study treatment initiation to the first occurrence of documented disease progression, as determined by the principal investigator (PI) review of tumor assessments using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause during the study.
V. Estimation of disease-free survival: disease-free survival, defined as the time from first postoperative computed tomography (CT) scan demonstrating no evidence of malignancy to the time of documented disease progression, as determined by the PI review of tumor assessments using RECIST v1.1, or death from any cause during the study.
VI. Estimation of the histopathologic response rate to neoadjuvant therapy and correlate it to survival outcomes.
TERTIARY OBJECTIVES:
I. Correlate the post therapeutic macropinocytosis with other exploratory markers and estimates of clinical outcomes.
II. Correlate pathologic response after neoadjuvant therapy with PFS stratified by ability to undergo surgical resection.
III. Correlate dynamic changes in stromal elasticity associated with chemotherapy administration and clinical outcomes.
IV. Correlate changes in serum cancer antigen 19.9 (CA19.9) and carcinoembryonic antigen (CEA) levels in response to therapy will be correlated with outcomes.
V. To correlate basal and dynamic changes in biomarkers of tissue secreted protein acidic and rich in cysteine (SPARC), mothers against decapentaplegic homolog 4 (SMAD4) deletion, circulating deoxyribonucleic acid (DNA) analysis of v-Ki-RAS2 Kirsten rat sarcoma 2 viral oncogene homolog gene (KRAS) and gene expression analysis with clinical outcomes.
OUTLINE:
Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30-40 minutes and gemcitabine hydrochloride IV over 30-40 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 21-35 days after completion of chemotherapy, patients undergo SBRT on 5 consecutive days over 1-2 weeks for a total of 5 fractions. Within 4-6 weeks after completion of SBRT, patients undergo pancreaticoduodenectomy or distal pancreatectomy. Within 6-12 weeks after surgery, patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30-40 minutes and gemcitabine hydrochloride IV over 30-40 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for 3 years.
Lead OrganizationUCHealth University of Colorado Hospital
Principal InvestigatorWells A. Messersmith
