Clinical trial NCT00398086: Gemcitabine Plus Albumin-bound Paclitaxel In Patients With Advanced Metastatic Pancreatic Cancer
Official title: A Phase I Trial of Gemcitabine (Gemzar) Plus ABI-007 (ABRAXANE) In Patients With Advanced Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: Metastatic Pancreatic Cancer, Abraxane, Gemcitabine
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2006-11-10
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the maximum tolerated dose and dose-limiting toxicity of Gemcitabine plus Albumin-bound paclitaxel (ABI-007) in patients with advanced metastatic pancreatic cancer.

Detailed description: Albumin-bound paclitaxel is a novel, solvent-free, albumin-bound, 130 nanometer particle form of paclitaxel designed to avoid the problems associated with solvents used in Taxol(Abraxane prescribing information 2005). Albumin has a number of properties that make it an attractive molecule to combine with paclitaxel. Albumin is a natural transporter of endogenous hydrophobic molecules such as water-insoluble vitamins and hormones (Vorum 1999)and albumin binding to the gp-60 receptor (albondin) initiates the caveolae-mediated endothelial transport of protein-bound and unbound plasma constituents (John et al 2003, Minshall et al 2003, Tiruppathi et al 1997).

This study consisted of a Phase 1 dose escalation phase, a Phase 2 treatment phase and a 24-month follow-up phase.

Eligibility criteria: Inclusion Criteria:

* Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell neoplasms are excluded.
* Male or non-pregnant and non-lactating female, and age greater or equal to 18.

  * If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test beta-human chorionic gonadotropin (B-hCG) documented within 72 hours of the first administration of study drug.
  * If sexually active, the patient must agree to use contraception considered adequate and appropriate by the investigator.
* Patient must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least 6 months after completing the last dose of gemcitabine.
* Patient has the following blood counts at baseline

  * Absolute neutrophil count (ANC) equal or greater to 1.5 x 10\^9/L;
  * Platelets equal or greater to 100 x 10\^9/L
  * Hemoglobin equal or greater to 9 g/dL.
  * Patient has the following blood chemistry levels at baseline:
  * Aspartate aminotransferase (SGOT), Alanine aminotransferase (SGPT) equal or less than 2.5 x upper limit of normal range (ULN) is allowed
  * Bilirubin less than or equal to ULN
  * Serum creatinine within normal limits or calculated clearance equal or greater to 60 mL/min/1.73M\^2 patients with serum creatinine levels above the institutional normal value
* Patient has no clinically significant abnormalities in urinalysis results
* Patient has acceptable coagulation status as indicated by a prothrombin time (PT) within normal limits (plus or minus 15%) and partial thromboplastin time (PTT) within normal limits (plus or minus 15%).
* Patient has a Karnofsky performance status (KPS) greater or equal to 70 (Eastern Cooperative Oncology Group \[ECOG\] PS 0-1).
* Patient has one or more metastatic tumors measurable by computed tomography (CT) scan.
* Patient has been informed about the nature of study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities.

Exclusion Criteria:

* Patient has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids and stable in two scans at least 4 weeks apart).
* Patient uses therapeutic coumadin for a history of pulmonary emboli and deep vein thrombosis (DVT).
* Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
* Patient has known infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C.
* Patient has undergone major surgery, other than diagnostic surgery i.e.-- done to obtain a biopsy for diagnosis without removal of an organ), with 4 weeks prior to Day 1 of treatment in this study.
* Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 3 weeks prior to study entry weeks (6 weeks for nitrosureas or mitomycin C).
* Patient has a history of allergy or hypersensitivity to the study drug.
* Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
* Patient is unwilling or unable to comply with study procedures.
* Patient is enrolled in any other clinical protocol or investigational trial.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities
timeFrame: Cycle 1 (Days 1-28)
Secondary outcomes:
measure: Number of Participants With Adverse Events (AE)
timeFrame: Up to 25 months
measure: Percentage of Participants Who Achieved an Objective Confirmed Overall Response
timeFrame: Up to approximately 4 years
measure: Percentage of Participants With Disease Control
timeFrame: Up to approximately 4 years
measure: Progression-free Survival
timeFrame: Up to approximately 4 years
measure: Duration of Response
timeFrame: Up to approximately 4 years
measure: Overall Survival
timeFrame: Up to approximately 4 years
measure: Maximal Degree of Myelosuppression
timeFrame: During the treatment phase, up to a maximum of 24 months.
measure: Maximal Degree of Anemia
timeFrame: During the treatment phase, up to a maximum of 24 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Ctr
state: Alabama
city: Scottsdale
country: United States
facility: Scottsdale Healthcare/Virginia Pipe Cancer Institute
state: Arizona
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
state: Maryland
city: Minneapolis
country: United States
facility: Virigina Piper Cancer Institute
state: Minnesota
city: San Antonio
country: United States
facility: South Texas Oncology & Hematology
state: Texas
Study officials:
affiliation: Scottsdale Clinical Research Institute
name: Daniel Von Hoff, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Korn RL, Von Hoff DD, Borad MJ, Renschler MF, McGovern D, Curtis Bay R, Ramanathan RK. 18F-FDG PET/CT response in a phase 1/2 trial of nab-paclitaxel plus gemcitabine for advanced pancreatic cancer. Cancer Imaging. 2017 Aug 3;17(1):23. doi: 10.1186/s40644-017-0125-5.