Gemcitabine+Nab-paclitaxel and FOLFIRINOX and Molecular Profiling for Patients With Advanced Pancreatic Cancer
Stage IV Pancreatic Cancer
Genetic: Immunohistochemistry (IHC) Analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Induction Consolidation and Maintenance Approach for Patients With Advanced Pancreatic Cancer|
- Complete Response Rate [ Time Frame: 1 yr. ] [ Designated as safety issue: No ]
The primary objectives of this study are to relentlessly pursue treatment for 34 individual patients with Stage IV pancreatic cancer to obtain:
• The complete response rate (as defined by a complete metabolomic response (CMR) of SUV normalization from baseline, OR a complete response on CT scan using a modified RECIST criteria and CA 19-9 (or CA 125, CEA, or PAM4 if not expressers of CA 19-9) down to normal limits (from at least > 2X ULN).
- One-Year Survival Endpoint [ Time Frame: 1 yr. ] [ Designated as safety issue: No ]
A secondary objective of this study is to:
Observe the percent of patients who are alive at one year (our goal is to obtain a >70% one year survival.)
- Efficacy Endpoints using biomarkers [ Time Frame: 1 yr. ] [ Designated as safety issue: No ]
A secondary objective of this study is to:
Gather information on other possible efficacy endpoints (e.g. CA 19-9) and other serum/plasma tumor markers
- Observing toxicity outcomes [ Time Frame: 1 yr. ] [ Designated as safety issue: Yes ]A secondary objective of this study is to document the toxicities noted in all patients, particularly with those who receive the FOLFIRINOX regimen. Grade 3-4 neutropenia is expected to be > 40% among those receiving FOLFIRINOX, so to minimize toxicity, all patients will receive prophylactic CGSF. In the first 9 patients receiving FOLFIRINOX, if the hospitalization rate due to toxicity is more than 50% (5 or more patients), then all subjects will have a dose reduction to level -1. The incidence of grade 3 and 4 toxicities and dose delays will also be considered for dose modification.
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Experimental: Gemcitabine & Abraxane Pancreatic Cancer
Gemcitabine+Nab-paclitaxel, FOLFIRINOX, Immunohistochemistry (IHC) Analysis, Metformin and Folfiri
1000 mg/m2 weekly on days 1,8, and 15 in a 28 day cycle. Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).
Other Name: GemzarDrug: nab-paclitaxel
125 mg/m2 on days 1,8, and 15 of a 28 day cycle Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).
Other Name: AbraxaneDrug: FOLFIRINOX
The combination below will be given on days 1 and 15 of a 28 day cycle; 5-Fluorouracil 2400 mg/m2 with a 46-hour continuous IV infusion; Leucovorin 400 mg/m2 over a 2 hour IV infusion;
Oxaliplatin 85 mg/m2 as a 2 hour IV infusion; Irinotecan 180 mg/m2 over a 90 minute IV infusion Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).
Other Names:Genetic: Immunohistochemistry (IHC) Analysis
Immunohistochemistry (IHC) Analysis will be performed on a fresh tissue biopsy of the tumor after chemotherapy has been administered. A targeted-based regimen will be determined from the results of the IHC analysis for the next therapy given to the patient in the maintenance phase of the study.Drug: Metformin
Metformin 500 mg daily as a 24 hour extended release tablet will also be given as part of the maintenance phase of this study.
Other Name: GlucophageDrug: mFOLFIRI
5-FU IV infusion, 2400 mg/m2 46h continuous infusion (no bolus 5-FU) treatments per month equaling 1 cycle Leucovorin 400 mg/m2 dl (over a 2 hour IV infusion) Irinotecan 180 mg/m2 dl (over a 90 minute IV infusion) Part A: nab-paclitaxel/Gem for 6 cycles, followed by FOLFIRINOX for 6 cycles (31 patients); Part B: Alternate nab-paclitaxel/Gem with mFOLFIRI every 2 months for up to 1 year or 6 cycles of each regimen (30 patients).
The investigators in the PCRT team have developed a therapeutic regimen which attacks both the tumor compartment and the stromal compartment of pancreatic cancer and induces complete responses in a small percentage of patients with advanced stage IV pancreatic cancer.
The gemcitabine + nab-paclitaxel regimen had outstanding activity in a 67 patient phase I/II trial with all patients at the recommended phase II doses (n=44) having a decrease in CA19-9, some complete responses and a median survival of 12.2 months. The proposed regimen that is devised for this study is a bold, innovative approach with the specific aim of utilizing a relentless pursuit approach to try to make the complete response rate >70% and have this response be durable (which the PCRT has defined as lasting at least 6 months) and to dramatically enhance the percent of patients who survive one year (try to make the rate >70%).
The induction regimen the investigators propose collapses the stroma (gemcitabine + nab-paclitaxel) and addresses the use of a non-cross resistant active regimen (FOLFIRINOX) as a consolidation regimen. Both should improve the chance of driving tumor markers down dramatically. The investigators think that FOLFIRINOX with the stromal collapse induced by the initial regimen, plus the totally non-cross resistant shot against the disease (consolidation), will maximize the chance of achieving a complete response with an attendant improvement in survival.
After the consolidation, the patient will be maintained on a less toxic targeted therapy selected by molecular profiling plus the use of the antimetabolomic agent metformin which has consistently been associated with better survival in multiple retrospective studies (Jiralerspong et al., 2009).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01488552
|United States, Arizona|
|TGen Clinical Research Services (TCRS)|
|Scottsdale, Arizona, United States, 85258|
|United States, California|
|Disney Family Cancer Center|
|Burbank, California, United States, 91505|
|United States, Minnesota|
|Virginia Piper Cancer Institute (VPCI)|
|Minneapolis, Minnesota, United States, 55407|
|United States, Washington|
|Virginia Mason Medical Center|
|Seattle, Washington, United States, 98101|
|Evergreen Hematology and Oncology|
|Spokane, Washington, United States, 99218|
|Principal Investigator:||Ramesh K Ramanathan, MD||Translational Genomics Research Institute, Phoenix, Arizona.|