Erlotinib and RAD001 (Everolimus) in Patients With Previously Treated Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: RAD001; Erlotinib
Intervention description: 30 mg orally weekly for 4 weeks; 150 mg by mouth daily for 28 Days
Intervention MeSH terms: Everolimus; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic Cancer; Advanced Pancreatic Cancer; Unresectable; Metastatic; RAD001; Everolimus; Erlotinib; OSI-774; Erlotinib Hydrochloride; Tarceva

Summary:

      The goal of this clinical research study is to learn if the combination of RAD001 and
      erlotinib hydrochloride can slow the growth of advanced pancreatic cancer. The safety of this
      drug combination will also be studied.

      Primary Objectives:

      -Determine the overall survival (OS) at 6 months of the combination of erlotinib and RAD001
      in patients who have received previous treatment for advanced pancreatic cancer.

      Secondary Objectives:

        -  Determine the progression-free survival (PFS).

        -  Determine the response rate (RR).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed advanced pancreatic
             adenocarcinoma that is unresectable or metastatic.

          -  Patients must have received at least one prior chemotherapy regimen for unresectable/
             metastatic disease. There is no limit to number of prior regimens. Prior erlotinib
             therapy is allowed.

          -  Minimum of two weeks since any major surgery, completion of radiation, or completion
             of all prior systemic anticancer therapy. Patients must have recovered from the acute
             toxicities of any prior therapy to NIH-NCI Common Terminology Criteria for Adverse
             Events (CTCAE) Version 3.0 </= Grade 1.

          -  Age >/= 18 years. Because no dosing or adverse event data are currently available on
             the use of erlotinib administered in combination with RAD001 in patients < 18 years of
             age, children are excluded from this study.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          -  Patients must have at least one measurable site of disease according to Response
             Evaluation Criteria In Solid Tumors (RECIST). This site must be outside a radiation
             field.

          -  Adequate hematologic, hepatic and renal parameters: leukocytes =/>3,000/ul, absolute
             neutrophil count =/>1,500/ul, platelets =/>100,000/ul, hemoglobin =/>9g/dL, total
             bilirubin </= 1.5 mg/dl, aspartate aminotransferase (AST) </=230 and alanine
             aminotransferase (ALT) </=280 IU/L for subjects with documented liver metastases; AST
             </=115 and ALT </=140 IU/L for subjects without evidence of liver metastases,
             creatinine </=1.5 mg/dl in males, </= 1.2 mg/dl in females.

          -  Women of childbearing potential (WOCBP) and men must agree to use adequate
             contraception prior to study entry for the duration of study treatment and 30 days
             after the end of treatment. WOCBP is defined as a woman who has not been naturally
             postmenopausal for at least 12 consecutive months or no previous surgical
             sterilization. Oral, implantable, or injectable contraceptives may be affected by
             cytochrome P450 interactions and are therefore not considered effective for this
             study. WOCBP must provide a negative pregnancy test (serum or urine) within 7 days
             prior to treatment.

          -  (Continuation of # 8) Acceptable contraception includes double-barrier methods (any
             double combination of: male or female condom with spermicidal gel, diaphragm, sponge,
             cervical cap, IUD).

          -  Signed 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:

          -  Prior treatment with any investigational drug within the preceding 2 weeks

          -  Chronic treatment with systemic steroids or another immunosuppressive agent. Patients
             can not receive immunization with attenuated live vaccines within one week of study
             entry or during study period

          -  Limits for fasting lipids must be: cholesterol </= 300mg/dL and triglyceride </= 2.5
             times upper limits of normal (ULN). Patients may be allowed to enroll on the trial
             after initiation of lipid lowering agents

          -  Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases (Brain imaging studies
             are not required if the patient does not have a history of brain metastases and has no
             neurological signs or symptoms)

          -  Other malignancies within the past 3 years except for adequately treated carcinoma of
             the cervix or basal or squamous cell carcinomas of the skin

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as: unstable angina
             pectoris, symptomatic congestive heart failure, myocardial infarction </= 6 months
             prior to first study treatment, serious uncontrolled cardiac arrhythmia; severely
             impaired lung function (oxygen dependent, Common Terminology Criteria (CTC) Grade 3 or
             4 dyspnea); uncontrolled diabetes as defined by fasting serum glucose >1.5 times ULN;
             any active (acute or chronic) or uncontrolled infection / disorders

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as: nonmalignant
             medical illnesses that are uncontrolled or whose control may be jeopardized by the
             treatment with the study therapy ; liver disease such as cirrhosis, known chronic
             active hepatitis or chronic persistent hepatitis; A known history of HIV
             seropositivity

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as: Impairment of
             gastrointestinal function or gastrointestinal disease that may significantly alter the
             absorption of RAD001 and/or erlotinib (e.g., ulcerative disease, uncontrolled nausea,
             vomiting, diarrhea, malabsorption syndrome or small bowel resection)

          -  Patients with an active, bleeding diathesis (if coumarin is used, weekly monitoring is
             recommended)

          -  Women who are pregnant or breast feeding, or women/men able to conceive and unwilling
             to practice an effective method of birth control. (Women of childbearing potential
             must have a negative urine or serum pregnancy test within 7 days prior to
             administration of RAD001). Oral, implantable, or injectable contraceptives may be
             affected by cytochrome P450 interactions, and are therefore not considered effective
             for this study. Acceptable contraception includes double-barrier methods (any double
             combination of: male or female condom with spermicidal gel, diaphragm, sponge,
             cervical cap, intrauterine device [IUD]).

          -  Patients who have received prior treatment with an mTor inhibitor

          -  Patients with a known hypersensitivity to erlotinib, RAD001 (everolimus) or other
             rapamycins (sirolimus, temsirolimus) or to its excipients