Intra-arterial Targeted Delivery of Gemcitabine in Treatment of Patients with Loco-regional Pancreatic Tumors

Transcription

1 Intra-arterial Targeted Delivery of Gemcitabine in Treatment of Patients with Loco-regional Pancreatic Tumors Alexander Rosemurgy, M.D., Sharona Ross, M.D., Paul Vitulli, M.D., Florida Hospital Tampa, Tampa, FL Reza Malek, M.D., Jiali Li, M.D., Ramtin Agah, M.D., El Camino Hospital Mountain View, CA

2 Disclosures The study was funded by RenovoRx (Los Altos, CA)

3 Aim: A dose escalation study of Gemcitabine for treatment of unresectable pancreatic cancer, using a targeted intra-arterial delivery catheter (RenovoCath ). Methods: 2 patients at two centers were enrolled with a fourstage dose escalation of gemcitabine up to 1 mg/m2. Enzyme markers, blood count, and constitutional endpoints were monitored to assess for dose-limiting toxicities. Feasibility and safety of repeated intra-arterial treatment sessions were assessed. Secondary endpoints included the effect on tumor size by imaging, tumor markers, and conversion to resectability. Results: Data for 2 patients enrolled is presented. Efficacy analysis was limited to the 15 patients who received more than two treatments.

4 Table 1. Treatment Regimen Cycle Day Chemotherapy Dose 1* Gemcitabine Gemcitabine 25 mg/m 2 25 mg/m Gemcitabine Gemcitabine 5 mg/m 2 5 mg/m Gemcitabine Gemcitabine 75 mg/m 2 75 mg/m Gemcitabine Gemcitabine 1 mg/m 2 1 mg/m 2 *Starting with patient RR1-19, the dose for the first cycle increased to 5 mg/m 2.

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6 Splenic artery narrowing with tumor impingement RenovoCath isolation of the tumor region with drug delivery

7 Table 2. Patient Characteristics Characteristic No. % Age, years Median Range Sex Male Female Stage of Tumor I II III IV Prior Treatment Yes No Prior Chemotherapy Only Yes No Prior Chemoradiation Yes No Prior Surgery Yes No % 55% 1% 55% 45% 25% 75% 3% 7% % 1%

8 Hematologic Neutropenia Thrombocytopenia Leukopenia Table 3. Toxicities (grade 3 and grade 4) Grade 3 Grade 4 Toxicity No. of Patients % No. of Patients % Non-hematologic Bilirubin Hyperglycemia Elevated Liver Function (LFP) Elevated Pancreatic Enzymes Gastritis % % % % % % % 5%

9 Table 4. Serious Adverse Events Parameter Vascular Visceral Arterial Dissection Requiring termination of further treatment Continuing further treatment Vascular access complication Hematoma (self-limited, conservative management) No. of Patients Non-Vascular Pulmonary Distress Sepsis Gastritis Duodenal Obstruction

10 Table 5. Efficacy: Tumor Response (clinical and or radiological progression), RECIST Criteria CT response, CA19-9 Parameter No. of Patients % Stable Disease Progression Partial Response CA 19-9 Reduction > 2% CA 19-9 Reduction % 2% 13% 6% 33%

11 RenovoCath treatment (>2 treatments): 43% survival Survival (%) % survival 2 RenovoCath greater than 2 treatments Average 4.4g/m2 of Gemcitabine (n=15) Months post Initial Diagnosis 11

12 RenovoCath treatment (8 treatments): 53% survival Survival (%) % survival 43% survival 2 1 RenovoCath completing 8 treatments Average 5.75g/m2 of Gemcitabine (n=9) RenovoCath greater than 2 treatments Average 4.4g/m2 of Gemcitabine (n=15) Months post Initial Diagnosis 12

13 RenovoCath treatment (>prior radiation): 75% survival % survival Survival (%) % survival 43% survival 2 1 RenovoCath prior chemoradiation therapy - Average 6.2g/m2 of Gemcitabine (n=7) RenovoCath completing 8 treatments Average 5.75g/m2 of Gemcitabine (n=9) RenovoCath greater than 2 treatments Average 4.4g/m2 of Gemcitabine (n=15) Months post Initial Diagnosis 13

14 Table 6. Prior chemoradiation vs. others, clinical response: Median Survival, CA19-9 reduction, CT response Prior Chemoradiation All Others P value (n=5) (n=1) Median Survival Survived more than two years post-diagnosis >2% CA 19-9 Reduction Consecutive CA 19-9 Reduction Tumor Size Reduction 846 days days P <.1 p <.5 P <.1 p<.5 P <.5

15 Survival: RenovoCath Effect + 15 months survival

16 Pre-Tx Tumor size: 2.8 x 3.3 x 4.1 Post-Tx Tumor size: 2.3 x 2.5 x 3.4

17 Trans-Arterial Micro-Perfusion Native tissue/vasculature + IA chemo Irradiated tissue/vasculature + IA chemo

18 Next Steps: RR3 Phase 3 Study Design Induction Phase Locally Advanced Pancreatic Cancer PATIENT ENROLLMENT IV Gem/ Abraxane 2 cycles Radiation IV Gem/ Abraxane 1 cycle CT Stable Progression RANDOMIZE Standard of care IA Gem 8 Treatments (biweekly) IV Gem/ Abraxane 4 Cycles IV Gem/ Abraxane IV Gem/ Abraxane

19 SUMMARY Intra-arterial delivery of gemcitabine using localized delivery catheter, RenovoCath, is safe provided: Patients with prior biliary stent/drain receive peri-op antibiotics IR training/support is necessary to avoid guide mediated vascular complications Early efficacy results of survival is encouraging, especially in patients with prior radiation where there may exist a synergistic effect with localized trans-arterial delivery of gemcitabine

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