1. Clinical IIT
Pancreatic Studies

2. Pancreatic Cancer
(ABX266) Andrew Ko / UCSF Phase I Study of Nab-paclitaxel, Gemcitabine & Capecitabine (AGX) in Previously Untreated, Metastatic Pancreatic Cancer
Key endpoints: MTD, Safety, TTP, ORR, OS, CA19-9 response
Phase I: nab-paclitaxel 100, 125, 150 mg/m2, FDR Gemcitabine
750, 1,000 mg/m2, day 4 every 14 days with Xeloda on days 1-7
750, 1000mg/m2 bid.
University of California, San Francisco, Huntsman Cancer Institute
Correlates: SPARC
n = 36
Phase I in 1st line, untreated pancreatic cancer
enroll
Nab-paclitaxel, Gemcitabine, Capecitabine
7/7/10: IRB approval for protocol version # 3, dated 4/31/10, contracting almost complete
7/19/10: study activated by Abraxis
7/27/10: study activated at UCSF
7/30/10: 1st patient on study at UCSF
8/11/10: IRB approval at Huntsman Cancer Institute, Dr Kim Jones is PI, contract partially signed on 8/18, waiting for Bruce’s signature
10/15/10: first 3 pts on dose level 0 (100/750/750), accrual on hold until pt 3 completes 3 cycle.
1/28/11: needed to expand dose level 1 due to 2 DLTs, currently have 4 pts on dose level 1, 4th pt on dose level is starting cycle 3, 2 pts from HCI.
Study will establish doses for weekly nab-paclitaxel, FDR Gemcitabine and Capecitabine using standard dose escalation schema with 3 to 6 patients per cohort (3+3 design). Will also correlate intratumoral expression of candidate markers mediating sensitivity to chemotherapy to clinical outcomes, including SPARC, DCK, RRM1. CA19-9 biomarker response rate (>50% decline in CA19-9 in patients with >2xULN at baseline). Protocol reviewed during week of 1/25/10 before IRB submission, IND Cross reference letter requested on 1/28, updated IB sent on 1/28/10. Trish ed Andrew on that support or SPARC testing withdrawn, Andrew was OK with that decision. Trish reviewed consent, version 1.3, dated on and consent contains needed language.
2nd site at the Huntsman Cancer Institute with Dr Kim Jones, separate contracts with each site.
Treatment: until progression or toxicity
Status: Active
FPI: 7/2010
Enrollment to date: 8 / 3 active
Publications to date: None

3. Pancreatic Cancer
(ABX271) Manuel Hidalgo / Centro Integral Oncologico Assessment of Stromal Response to Nab-paclitaxel in combination with gemcitabine in Operable Pancreatic Cancer
Primary endpoints:
Evaluate the effect on tumor stroma density
Evaluate the effect on tumor vessel formation
Evaluate the effect of nab-paclitaxel on tumor metabolism
Secondary endpoints:
Evaluate combination treatment activity in relation with biological changes in tumor stroma and tumor metabolic activity
Assess the impact of SPARC expression in tumor and stroma
n = 15
Stage I – III
Pancreatic
cancer
Study start delayed (from July 2010 to September 2010) due to limited drug availability in Europe.
Nab-paclitaxel 125 mg/m2 weekly
Gemcitabine 1000 mg/m2 weekly
enroll
Status: Active
FPI: n/a
Enrollment to date: 0 / 0 active
Publications to date: none
Treatment: 2 cycles Surgery

4. Pre-clinical Pancreatic Study
(ABX273) Manuel Hidalgo / Centro Integral Oncologico Targeting Pancreatic Cancer Stroma
Human pancreatic ductal adenocarcinoma xenografts
Murine model
Aim 1: To determine the effects of combining nab-paclitaxel with other stroma targeting agents hedgehog inhibitors (CUR199691) either alone or in combination with gemcitabine, capecitabine and oxaliplatin
Aim 2: To assess the effects of sequential promotion and inhibition of blood vessel formation. It will determine the metastasis promoting effects of anti-stromal drugs as well as the effects of sequential combination of maximal anti-stroma treatments with angiogenesis inhibitors
Activated: 10/5/2010 (5% complete)
Publications to date: None