BrUOG-PA-209: Lapatinib and Gemcitabine for Metastatic Pancreaticobiliary Cancer
Condition: Metastatic Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Gemcitabine 1000mg/m2 30 minutes; Lapatinib 1000mg/d; Lapatinib 1500mg/d; Gemcitabine 1000mg/m2 100minutes; Oxaliplatin 100mg/m2
Intervention description: 1000mg/m2 30 minutes; 1000mg/d; 1500mg/d; 1000mg/m2 100minutes; 100mg/m2
Intervention MeSH terms: Gemcitabine; Oxaliplatin; Lapatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic Cancer

Summary:

      Phase I study of lapatinib and gemcitabine for patients with metastatic pancreaticobiliary
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients are required to have histologically or pathologically confirmed, metastatic
             adenocarcinoma of the pancreas

          -  No prior chemotherapy for pancreatic cancer.

          -  ECOG performance status 0-1

          -  Must retain ability to swallow oral medications

          -  Age > 18. Because no dosing or adverse event data are currently available on the use
             of lapatinib in patients < 18 years of age, children are excluded from this study.

          -  Women of child bearing potential must be non pregnant and non lactating.The effects of
             lapatinib on the developing human fetus at the recommended therapeutic dose are
             unknown. For this reason, women of child bearing potential and men must agree to use
             adequate contraception (hormonal or barrier method of birth control or 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. A female is eligible to enter and
             participate in the study if she is of:

               -  Non-childbearing potential (i.e., physiologically incapable of becoming
                  pregnant), including any female who:

                    -  Has had a hysterectomy,

                    -  Has had a bilateral oophorectomy (ovariectomy),

                    -  Has had a bilateral tubal ligation, or

                    -  Is post-menopausal(demonstration of total cessation of menses for ³1 year).

               -  Childbearing potential, has a negative serum pregnancy test within 2 weeks prior
                  to treatment to rule out pregnancy.

               -  Men and women of childbearing potential must be willing to consent to using
                  effective contraception while on treatment.

                    -  Intrauterine Device (IUD),

                    -  Vasectomized partner who is sterile prior to the female subject's entry and
                       is the sole sexual partner for that female.

                    -  Complete abstinence from sexual intercourse for two weeks before exposure to
                       investigational products, throughout the clinical trial, and for at least
                       one week after the last dose of investigational product.

                    -  Double barrier contraception (condom with spermicidal jelly, foam,
                       suppository, or film; diaphragm with spermicide; or male condom and
                       diaphragm).

                    -  Vasectomy

          -  Adequate hematologic function: ANC ≥ 1500/ul, platelets ≥ 100,000/ul. Adequate hepatic
             function with total bilirubin ≤ 2.0 mg/dL and ALT or AST ≤ 2x ULN. (Patients with
             liver metastases may have AST/ALT less than or equal to 5x upper limit of normal).

          -  Adequate renal function: creatinine ≤ 2.0 mg/dL

          -  Cardiac ejection fraction within the institutional range of normal as measured by
             echocardiogram or MUGA scan. Note that baseline and on treatment scans should be
             performed using the same modality and preferably at the same institution.

          -  Life expectancy of at least 12 weeks

          -  Signed informed consent

        Exclusion Criteria:

        A subject will not be eligible for inclusion in this study if any of the following criteria
        apply:

          -  Prior treatment with lapatinib or any EGFR targeting therapies.

          -  Prior treatment with systemic chemotherapy for pancreatic cancer.

          -  Clinical evidence of brain metastases or leptomeningeal disease

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Active cardiac disease, defined as:

               -  History of uncontrolled angina

               -  Myocardial infarction < 6 months from study entry

               -  Uncontrolled or symptomatic congestive heart failure

               -  Ejection fraction below the institutional normal limit

               -  Any other cardiac condition, which in the opinion of the treating physician,
                  would make this protocol unreasonably hazardous for the patient

          -  The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy
             to drugs chemically related to the study drug.

          -  HIV-positive patients receiving combination anti-retroviral therapy are excluded from
             the study because of possible pharmacokinetic interactions with lapatinib

          -  Participation in any investigational study within 28 days prior to study enrolment

          -  Any major surgery (insertion of a vascular access device or laparoscopy is not
             considered a major surgery), within the last 4 weeks.

          -  Pregnant or lactating females are excluded from this study because lapatinib is member
             of the 4-anilinoquinazoline class of kinase inhibitors with the potential for
             teratogenic or abortifacient effects. Because there is an unknown but potential risk
             for adverse events in nursing infants secondary to treatment of the mother with
             lapatinib, breastfeeding should be discontinued if the mother is treated with
             lapatinib.

          -  Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function
             or major resection of the stomach or small bowel that could affect absorption of
             lapatinib.

          -  Any unresolved bowel obstruction.

          -  The patient has inadequate venous access in the clinical judgment of the investigator
             or designated clinical staff.

          -  Patient is taking any medication on the prohibited medications list in

          -  Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided
             there is increased vigilance with respect to monitoring INR. If medically appropriate
             and treatment available, the investigator may also consider switching these patients
             to LMW heparin, where an interaction with lapatinib is not expected.

          -  Patients may not be receiving any other investigational agents or receiving concurrent
             anticancer therapy.