Bortezomib and Carboplatin in Treating Patients With Metastatic Pancreatic Cancer
Condition: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Stage IV Pancreatic Cancer
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Carcinoma, Acinar Cell
Intervention: bortezomib; carboplatin; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Correlative studies
Intervention MeSH terms: Carboplatin; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bortezomib together with carboplatin works in
      treating patients with metastatic pancreatic cancer. Bortezomib may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy,
      such as carboplatin, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Giving bortezomib together with
      carboplatin may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed adenocarcinoma or
             carcinoma of the pancreas that is metastatic and not amenable to resection with
             curative intent

          -  Patients must have measurable disease defined by RECIST criteria; for the purpose of
             this study, primary mass in the pancreas is not considered as measurable disease

          -  Patients must have received one (1), and only one, prior systemic regimen for
             metastatic disease; patients who have received prior cisplatin or oxaliplatin are
             eligible; a systemic regimen administered for unresectable locally advanced disease
             that subsequently progressed to metastatic will be counted as 1 prior regimen;
             chemotherapy administered as adjuvant therapy or as a radiation sensitizer is not
             counted as a prior regimen

          -  Prior radiation is permitted; however, at least 3 weeks must have elapsed since the
             completion of prior radiation therapy and patients must have recovered from all
             associated toxicities to NCI Common Terminology Criteria for Adverse Events (CTCAE)
             Version 3.0 ≤ Grade 1 at the time of registration; measurable disease must be outside
             the previous radiation field or a new lesion inside the port must be present

          -  At least two weeks must have elapsed since any major surgery and patients must have
             recovered from all associated toxicities to ≤ CTCAE Grade 1 at the time of
             registration

          -  At least 4 weeks must have elapsed since previous chemotherapy except for regimens
             that are administered on a daily, weekly, or every other week schedule, in which case
             at least 2 weeks must have elapsed since previous chemotherapy; patients must have
             recovered from all associated toxicities to CTCAE ≤ Grade 1 at the time of
             registration

          -  ECOG performance status =< 1 (Karnofsky >= 70%)

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin ≥ 9 g/dl

          -  Total bilirubin =<1.5 X institutional upper limit of normal

          -  AST (SGOT) & ALT (SGPT) =< 2.5 X institutional upper limit of normal or =< 5 X
             institutional upper limit of normal if patient has liver metastasis

          -  Creatinine ≤ 1.5 mg/dL OR creatinine clearance >= 60 mL/min/1.73 m2 for patients with
             creatinine levels above institutional normal

          -  Other prior malignancy is allowed as long as the patient does not require active
             treatment for their second malignancy and there is no radiographic evidence of second
             malignancy; patients who are receiving hormonal therapy for breast or prostate cancer
             as adjuvant treatment are eligible

          -  The effects of bortezomib on the developing human fetus at the recommended therapeutic
             dose are unknown; for this reason and because carboplatin, the other therapeutic agent
             used in this trial, is known to be teratogenic, women of child-bearing potential and
             men of reproductive potential must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to study entry and for the duration
             of study participation; should a woman become pregnant or suspect she is pregnant
             while participating in this study, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document;
             written informed consent must be obtained prior to any evaluations being performed
             solely for the purposes of screening for eligibility for this study

        Exclusion Criteria:

          -  Patients who have only locally advanced disease (not metastatic) are excluded

          -  Patients who have received prior treatment with carboplatin, bortezomib, or another
             proteasome inhibitor are excluded

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events;
             however, brain imaging studies are not required to assess eligibility if the patient
             has no neurological signs or symptoms

          -  Patients with current neurotoxicity, defined as greater than CTCAE Grade 1
             neurotoxicity

          -  Patients must not be planning to receive any other concomitant anticancer treatment
             including chemotherapy, radiation therapy, biologic agents, or any other
             investigational drugs

          -  Patients must not have significant history of cardiac disease, i.e., unstable angina,
             congestive heart failure with New York Heart Association class 3 or 4, and myocardial
             infarction within the last 6 months

          -  Pregnant women are excluded from this study because bortezomib is a proteasome
             inhibitor agent with the potential for teratogenic or abortifacient effects;
             carboplatin has been shown to be embryotoxic and teratogenic in rats; because there is
             an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with bortezomib and carboplatin, breastfeeding should be
             discontinued if the mother is treated with these drugs

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with bortezomib and carboplatin; in
             addition, these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy; appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated