Clinical trial NCT01298011: Study of Gemcitabine and Abraxane to Treat Potentially Operable Pancreatic Cancer
Official title: A Pilot Phase II Multi Center Study of Gemcitabine and Nab-paclitaxel (Abraxane) as Preoperative Therapy for Potentially Operable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Resectable Pancreatic Cancer
Keywords: operable
pancreas
Abraxane
Gemcitabine
Preoperative
potentially
Pancreatic Cancer
Lead sponsor: Pancreatic Cancer Research Team
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2011-02-17
Enrollment: 25
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 main purpose of this research study is to evaluate whether Abraxane and gemcitabine are effective in treating patients with operable pancreatic cancer.

Detailed description: The best outcome for a patient diagnosed with pancreatic cancer is surgery. However many patients have recurrence of the cancer after successful surgery. The investigators are evaluating chemotherapy before surgery, which is a new approach.

In this study, Abraxane and gemcitabine will be tested as treatment for people with operable pancreatic cancer to see if surgery can be successfully performed and if treatment will reduce cancer cells in the tumor at surgery.

Abraxane is approved by the US FDA for the treatment of metastatic breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Gemcitabine is approved by the FDA for first line treatment for patients with locally advanced or metastatic cancer of the pancreas.

Eligibility criteria: Inclusion Criteria:

1. Patient has histologically or cytologically confirmed potentially resectable adenocarcinoma of the pancreas. Patients with islet cell neoplasms are excluded.

   Definition of potentially operable disease
   1. Staging by high-quality, pancreatic protocol, helical abdominal computed tomography required (Endoscopic ultrasound is not required).
   2. No extension to superior mesenteric artery (SMA) and hepatic artery.
   3. Clear fat plane between the SMA and celiac axis.
   4. No extension to celiac axis and hepatic artery.
   5. Patent superior mesenteric vein and portal vein.
   6. No evidence of distant or extra-hepatic disease by CT scans.
   7. Pretreatment histological or cytological confirmation of an adenocarcinoma.
2. Male or non-pregnant and non-lactating female, and ≥ 18 years of age.
3. If a female patient is of child-bearing potential, she must have a negative serum pregnancy test (β hCG) documented within 72 hours of the first administration of study drug.
4. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator.
5. Patient must have received no prior chemotherapy or radiation for pancreatic cancer and no exposure to gemcitabine and/or Abraxane
6. Patient has the following blood counts at baseline:

   1. ANC ≥ 1.5 x 109/L (1500 /mm³);
   2. Platelets ≥ 100 x 109/L; (100,000/mm³);
   3. Hgb ≥ 10 g/dL.
7. Patient has the following blood chemistry levels at baseline:

   1. AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal (ULN);
   2. Alkaline phosphatase (AP) ≤ 2.5 X ULN;
   3. Total bilirubin ≤1.5 mg/dl;
   4. Serum creatinine ≤1.5mg/dl or calculated clearance ≥ 50 mL/min/1.73 m² for patients with serum creatinine levels \>1.5 mg/dl.
8. Patient has acceptable coagulation status as indicated by a PT within normal limits (±15%) and PTT within normal limits (± 15%).
9. Patient has an ECOG performance status PS 0-1.
10. Patient has been informed about the nature of the 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:

1. Patient has borderline resectable disease
2. Patient uses therapeutic coumadin for a history of pulmonary emboli or DVT.
3. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
4. Patient has known infection with HIV, hepatitis B, or hepatitis C.
5. Patient has undergone major surgery, other than diagnostic surgery (i.e.--surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
6. Prior chemotherapy or radiation for pancreatic cancer. Prior exposure to gemcitabine and/or Abraxane.
7. Patient has a history of allergy or hypersensitivity to the study drugs.
8. 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.
9. Patient is unwilling or unable to comply with study procedures.
10. Patient is enrolled in any other therapeutic clinical protocol or investigational trial.
11. Patient has metastatic disease on radiological staging.
12. Patients aged ≥ 80 are not excluded. As two events of fatal sepsis have been seen in this group in other studies, candidates in this age group should be thoroughly evaluated before enrollment in the study, to ensure they are fit to receive chemotherapy. In addition to meeting all of the baseline patient selection criteria, clinical judgment on their susceptibility to infection and expected stability of their performance status as to receive repeat weekly chemotherapy cycles, should be paid special attention to. Patients should not be enrolled in the study should there be any hesitation on any of these considerations. Baseline criteria for all patients enrolled on the study must be carefully evaluated and all criteria followed appropriately.

Primary outcomes:
measure: Grade III/IV histological response in tumor specimen rate after induction therapy.
timeFrame: At time of surgery
Secondary outcomes:
measure: Number of participants with adverse events.
timeFrame: From the initial dose of study drug up to 28 days after last dose of study drug.
measure: Tumor response rate to therapy.
timeFrame: Baseline and 16 weeks
measure: Change in CA 19-9
timeFrame: Baseline, Day 1 of each cycle, and end of therapy.
measure: Resection rate at surgery
timeFrame: At time of surgery
measure: Time to recurrence
timeFrame: Time from first dose of study drug to date of first documented progression or date of death, whichever occurs first, assessed up to 60 months.
measure: SPARC protein expression in tumor
timeFrame: At time of surgery
measure: Overall Survival
timeFrame: Time from the first dose of study drug until date of death from any cause, up to 60 months.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TGen Clinical Research Services at Scottsdale Healthcare
state: Arizona
city: Grand Rapids
country: United States
facility: St Mary's / Trinity Health Care
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Pittsburg
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
Study officials:
affiliation: TGen Drug Development
name: Ramesh K. Ramanathan, MD
role: PRINCIPAL_INVESTIGATOR
References: