Gemcitabine+Nab-paclitaxel and FOLFIRINOX and Molecular Profiling for Patients With Advanced Pancreatic Cancer

NCT01488552 | Completed Phase 1

• 1 other identifier: PCRT 11-002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

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.

Conditions

Stage IV Pancreatic Cancer

Keywords

pancreatic cancer; pancreatic adenocarcinoma; Stage IV pancreatic cancer; pancreas; pancreatic

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  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).

  1 yr.

Secondary Outcomes (3)

• One-Year Survival Endpoint

  1 yr.

• Efficacy Endpoints using biomarkers

  1 yr.

• Observing toxicity outcomes

  1 yr.

Study Arms (1)

Gemcitabine & Abraxane Pancreatic Cancer

EXPERIMENTAL

Gemcitabine+Nab-paclitaxel, FOLFIRINOX, Immunohistochemistry (IHC) Analysis, Metformin and Folfiri

Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: FOLFIRINOX; Genetic: Immunohistochemistry (IHC) Analysis; Drug: Metformin; Drug: mFOLFIRI

Interventions

Gemcitabine DRUG

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).

Also known as: Gemzar

Gemcitabine & Abraxane Pancreatic Cancer

nab-paclitaxel DRUG

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).

Also known as: Abraxane

Gemcitabine & Abraxane Pancreatic Cancer

FOLFIRINOX DRUG

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).

Also known as: 5-FU, Eloxitan, Campostar

Gemcitabine & Abraxane Pancreatic Cancer

Immunohistochemistry (IHC) Analysis GENETIC

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.

Gemcitabine & Abraxane Pancreatic Cancer

Metformin DRUG

Metformin 500 mg daily as a 24 hour extended release tablet will also be given as part of the maintenance phase of this study.

Also known as: Glucophage

Gemcitabine & Abraxane Pancreatic Cancer

mFOLFIRI DRUG

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).

Gemcitabine & Abraxane Pancreatic Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pancreatic Cancer Research Team: lead

Study Sites (5)

TGen Clinical Research Services (TCRS)

Scottsdale, Arizona, 85258, United States

Location

Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Virginia Piper Cancer Institute (VPCI)

Minneapolis, Minnesota, 55407, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Evergreen Hematology and Oncology

Spokane, Washington, 99218, United States

Location

Related Publications (2)

• 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.

  PMID: 21561347 BACKGROUND

• 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.

  PMID: 21969517 BACKGROUND

Related Links

• Additional information about the Pancreatic Cancer Research Team (PCRT)
• Non-profit Organization
• Related link
• Non-profit organization for pancreatic cancer research

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; folfirinox; Fluorouracil; Immunohistochemistry; Metformin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Uracil; Pyrimidinones; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Biguanides; Guanidines; Amidines

Study Officials

• Ramesh K Ramanathan, MD

  Translational Genomics Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2011
• First Posted: December 8, 2011
• Study Start: November 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2016
• Last Updated: August 18, 2016

Record last verified: 2016-08

Locations

US (5)