Clinical trial NCT01488552: Gemcitabine+Nab-paclitaxel and FOLFIRINOX and Molecular Profiling for Patients With Advanced Pancreatic Cancer
Official title: A Phase II Study of Induction Consolidation and Maintenance Approach for Patients With Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Stage IV Pancreatic Cancer
Keywords: pancreatic cancer
pancreatic adenocarcinoma
Stage IV pancreatic cancer
pancreas
pancreatic
Lead sponsor: Pancreatic Cancer Research Team
Sponsor class: OTHER
First posted: 2011-12-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Histologically documented Stage IV metastatic adenocarcinoma of the pancreas with measurable disease
* Performance status ECOG 0 or 1
* Patients may not have received prior treatment for metastatic pancreatic adenocarcinoma except for receiving gemcitabine or 5FU as a radiosensitizer along with radiation therapy; or have received gemcitabine for adjuvant treatment if they have been off gemcitabine for \> 12 months
* Adult (\>18 years of age) male or non-pregnant and non-lactating female
* A negative serum pregnancy test (Beta-hCG) documented within 72 hours of the first administration of study drug in female patients of child-bearing potential
* Agreement to use contraception considered adequate and appropriate by the investigator
* The following blood counts at baseline:

  * ANC \>/= 1.5 x 109/L
  * Hgb \> 9g/dL
  * Platelets \>100 x 109/L
* The following blood chemistry levels at baseline:

  * AST and ALT \</= 2.5 x upper limit of normal range (ULN) or \< 5.0 ULN if liver metastasis are present
  * Bilirubin \</= ULN
  * Serum creatinine within 1.5 x ULN
* PT, INR within 1.5 x ULN unless on therapeutic doses of warfarin
* Must have measurable disease outside the pancreas by RECIST criteria
* No clinically significant abnormalities in urinalysis results
* Voluntary agreement to participate in this study after being informed about the nature of the study including potential risks and benefits and having the ability to have questions addressed. The patient must sign and date the IRB approved Informed Consent Form (ICF) prior to participation in any study-related procedures

Exclusion Criteria:

* Has pancreatic islet cell neoplasms
* Is pregnant or lactating
* Has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
* Known infection with HIV, Hepatitis B or Hepatitis C.
* Patient with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies (see section 4.4.9)
* Has a serious medical risk factor(s) involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
* Is unwilling or unable to comply with study procedures.
* Is enrolled in any other investigational trial.

Caution of observation for interstitial pneumonitis in patients prior to enrollment:

Before enrollment, evaluate candidate patients fro familial, environmental or occupational exposure to opportunistic pathogens, and do not enroll those with a history of slowly progressive dyspnea and unproductive cough, or of conditions such as sarcoidosis, silicosis. idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

Primary outcomes:
measure: Complete Response Rate
timeFrame: 1 yr.
Secondary outcomes:
measure: One-Year Survival Endpoint
timeFrame: 1 yr.
measure: Efficacy Endpoints using biomarkers
timeFrame: 1 yr.
measure: Observing toxicity outcomes
timeFrame: 1 yr.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TGen Clinical Research Services (TCRS)
state: Arizona
city: Burbank
country: United States
facility: Disney Family Cancer Center
state: California
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute (VPCI)
state: Minnesota
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Spokane
country: United States
facility: Evergreen Hematology and Oncology
state: Washington
Study officials:
affiliation: Translational Genomics Research Institute
name: Ramesh K Ramanathan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.
citation: Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. doi: 10.1200/JCO.2011.36.5742. Epub 2011 Oct 3.