RAINIER: A randomized, double-blinded, placebo-controlled phase II trial of gemcitabine (gem) plus nab-paclitaxel (nab-P) combined with apatorsen (A) or placebo (Pl) in patients (pts) with metastatic pancreatic cancer (mPC).

Authors

Andrew Ko

Andrew H. Ko

University of California, San Francisco, San Francisco, CA

Andrew H. Ko , Patrick B. Murphy , James D. Peyton , Dianna Shipley , Ahmed Al-Hazzouri , Frank A. Rodriguez , Mark S. Womack IV, Henry Q. Xiong , David M. Waterhouse , Margaret A. Tempero , Johanna C. Bendell

Organizations

University of California, San Francisco, San Francisco, CA, Tennessee Oncology, PLLC, Sarah Cannon Research Institute, Nashville, TN, Florida Cancer Specialists, Sarah Cannon Research Institute, Fort Myers, FL, The Center for Cancer and Blood Disorders, Sarah Cannon Research Institute, Fort Worth, TX, Oncology Hematology Care, Sarah Cannon Research Institute, Cincinnati, OH, Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN

Research Funding

Other

Background: Heat shock protein 27 (Hsp27) is over-expressed in PC, enabling tumor growth and metastasis. A is an antisense oligonucleotide that binds to Hsp27 mRNA and inhibits production of Hsp27 protein. This randomized phase II trial evaluates the efficacy of gem/nab-P plus A or Pl in pts with mPC. Methods: Pts with untreated mPC were randomized 1:1 to Arm A (gem, nab-P, A) or Arm B (gem, nab-P, Pl). 3 loading doses of 600mg A IV or Pl IV were given, then 600 mg A or Pl weekly with chemotherapy in 28 day cycles. Both arms received gem 1000mg/m2 IV, nab-P 125mg/m2 IV days 1, 8, and 15. Restaging was every 2 cycles. Serum Hsp27 levels were collected at baseline and on treatment. Primary endpoint compared overall survival (OS); secondary endpoints were progression free survival (PFS), response rate (RR), CA 19-9 response, and toxicity. Results: 132 pts were randomized: median age 66 yrs, 57% male, 47% ECOG 0. Demographics were similar for both arms. 36% of pts on Arm A and 48% of pts Arm B discontinued due to progressive disease, and 24% and 14% due to adverse events (AEs). There was a higher incidence of ≥Grade (G) 4 and serious adverse events (SAEs) in Arm A. The most frequently reported G 3/4 treatment-related AEs were anemia (20%), neutropenia (17%), and fatigue (16%) on Arm A and anemia (27%), neutropenia (19%), and thrombocytopenia (13%) on Arm B. Overall RR was 18% on each arm. With a median f/u of 9.1 mos, median PFS and OS are 2.7 and 5.2 mos on Arm A and 3.8 and 6.9 mos on Arm B (p=NS). Correlative analyses between Hsp27 expression and clinical outcomes will be presented. In a statistical model using only Arm B data, 3 base attributes, ECOG >0, liver mets, and neutrophil levels had a strong prognostic relationship to OS. Conclusions: This study showed no improvement in clinical outcomes adding A to gem plus nab-p. G 4 AEs and SAEs were increased with A. We await analysis for Hsp 27 and CA 19-9 levels and further analysis to identify any pt subgroup who might have benefited from the experimental treatment. Clinical trial information: NCT01844817

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Abstract Details

Meeting

2016 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Track

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Sub Track

Multidisciplinary Treatment

Clinical Trial Registration Number

NCT01844817

Citation

J Clin Oncol 34, 2016 (suppl 4S; abstr 419)

DOI

10.1200/jco.2016.34.4_suppl.419

Abstract #

419

Poster Bd #

L13

Abstract Disclosures