Clinical trial NCT01470417: Gemcitabine With Abraxane and Other Investigational Therapies in Neoadjuvant Treatment of Pancreatic Adenocarcinoma
Official title: GAIN-1 Study: Gemcitabine With Abraxane and Other Investigational Therapies in Neoadjuvant Treatment of Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2011-11-11
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the role of Gemcitabine and Abraxane in the treatment of resectable and borderline-resectable pancreatic cancer by giving the chemotherapy before surgery.

Detailed description: This current study proposes to conduct a prospective non-randomized open-label phase II trial using Gemcitabine and Abraxane in the neoadjuvant treatment of resectable and borderline-resectable pancreatic cancer. For patients that are low-risk resectable (based on prediction rule) the plan is to administer 2 cycles of Gemcitabine and Abraxane followed by additional systemic therapy or chemotherapy with radiation therapy (chemoRT), followed by surgical resection. For patients who are either borderline-resectable or high-risk resectable (see schema), the plan is to administer 2 cycles of Gemcitabine and Abraxane followed by chemoradiotherapy concurrent with gemcitabine followed by surgical resection. For those without high-risk features, systemic chemotherapy alone will be administered. The primary endpoints will be R0 surgical resection rate, biochemical (CA 19-9), pathologic and radiologic response rates. Secondary endpoints will include progression-free survival (PFS), overall survival (OS), 30-day post-op mortality, toxicity, quality of life, pain control, and correlative molecular exploratory analysis involving pancreatic tumor and stromal SPARC expression levels. The investigators will also assess the patient, tumor, and clinical characteristics that may predict R0 resectability, thus further refining the predictive rule in high-risk patients as defined by Bao and colleagues. The investigators' hypothesis is that by using targeted and risk-adapted chemotherapy or chemoRT, improved R0 surgical resections can be achieved and effective systemic therapy delivered, which will translate to a significant improvement in overall survival in patients with pancreatic adenocarcinoma, compared to published historical controls.

Eligibility criteria: Inclusion Criteria:

* • Histologically or cytologically confirmed adenocarcinoma of the pancreas.

  * Patients must have locally advanced pancreatic cancer, classified as either low-risk resectable (LR), high-risk resectable (HR) or borderline resectable (BR)
  * Age between 18 and 90 years at the time of consent.
  * Patients with biliary obstruction must have adequate drainage prior to starting treatment.
  * Patients must have ≤ Grade I peripheral neuropathy (CTCAE v 4.0)
  * Patients must have ≤ ECOG Performance status 2
  * Pretreatment laboratory parameters:

    * Absolute granulocyte/neutrophil count (AGC/ANC) ≥ 1.8 thou/mm3
    * Platelet count ≥ 100,000/mm3
    * Bilirubin \< 2 mg/dl
    * ALT/SGPT \< 10x upper limit of normal
    * Creatinine \< 3 mg/dl
    * Calculated creatinine clearance (via Cockcroft-Gault) \> 30 mL/min
    * Baseline CA 19-9 levels
  * Signed study specific, IRB stamped informed consent

Exclusion Criteria:

* • Evidence of any distant metastasis including peritoneal seeding and/or malignant ascites

  * Previous irradiation to the abdomen that would compromise the ability to deliver the prescribed treatment
  * Prior treatment for pancreatic cancer
  * Active, untreated infection
  * Surgical resection of the tumor (not including biopsies)
  * Other malignancy (except non-melanoma skin cancer) that has not been disease-free for at least 5 years.
  * Pregnant and/or breast-feeding women, or patients (men and women) of child-producing potential not willing to use medically acceptable contraception while on treatment and for at least 3 months thereafter.
  * Use of anti-epileptics (drugs such as phenytoin, phenobarbitol and carbamazepine)
  * ECG abnormality with the following: QTC \>500, left bundle branch block or any other clinically significant finding that would interfere with protocol therapy.
  * History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician

Primary outcomes:
measure: Biochemical Response Rate
timeFrame: 4 - 8 weeks after neoadjuvant therapy
measure: Radiographic Response Rate
timeFrame: 4 - 8 weeks after neoadjuvant therapy
measure: Pathologic Downstaging and Margin Status
timeFrame: At the time of surgery after neoadjuvant therapy
Secondary outcomes:
measure: 90 Day Post-operative Mortality
timeFrame: 90 days after surgery
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
Study officials:
affiliation: University of Florida
name: Thomas George, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References: