Erlotinib and RAD001 (Everolimus) in Patients With Previously Treated Advanced Pancreatic Cancer

• Status: Terminated
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborators: Novartis; OSI Pharmaceuticals
• Treatments: Erlotinib Hydrochloride; Everolimus; Sirolimus

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
• 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 bilirubinaminotransferase (ALT)creatinine
• 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: cholesteroltimes 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 infarctionprior 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