A Study of GDC-0449 and Erlotinib Hydrochloride, with or without Gemcitabine Hydrochloride for Treating Patients with Metastatic Pancreatic Cancer or Solid Tumors that cannot be Removed by Surgery

Overview

  • Study type

    Interventional
  • Study phase

    I
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 08-005693
    • Jacksonville, Florida: 08-005693
    • Rochester, Minnesota: 08-005693
    NCT ID: NCT00878163
    Sponsor Protocol Number: MC0811

About this study

The purpose of this study is to determine the side effects and best dose of erlotinib hydrochloride when given together with GDC-0449, and either with or without gemcitabine hydrochloride, for the treatment of patients who have metastatic pancreatic cancer or solid tumors that cannot be removed by surgery. Drugs used in chemotherapy, such as GDC-0449 and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving GDC-0449 together with erlotinib hydrochloride with or without gemcitabine hydrochloride may kill more tumor cells.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria

  • Histologic proof of a solid tumor that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy
  • Metastatic adenocarcinoma of the pancreas amenable to biopsies (cohort II MTD only)
  • Absolute neutrophil count (ANC) ≥ 1,500/μL
  • Platelets ≥ 100,000/μL
  • Total bilirubin ≤ upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 3 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • Hemoglobin ≥ 9.0 g/dL
  • International Normalized Ratio (INR) within normal limits (for patients treated at the MTD)
  • Ability to provide informed consent
  • Willing to return to Mayo Clinic for follow up
  • Life expectancy ≥ 12 weeks
  • Willing to provide the biologic specimens as required by the protocol
  • Negative serum pregnancy test done ≤ 7 days prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Able to swallow or have medication administered through a G-tube and absorb the medication
  • Agrees to use an acceptable form of contraception, which are
    • Latex condom (always used with spermicide)
    • Diaphragm (always used with spermicide)
    • Cervical cap (always used with spermicide)
  • Acceptable forms of secondary contraception, when used along with a barrier method
    • Hormonal contraception methods, including pills, patches, rings, or injections except progestin-only containing pills (i.e. "Mini-pill")
    • Tubal ligation
    • Partner's vasectomy
    • Intrauterine device (IUD) (non-progesterone T)
    • Vaginal sponge (containing spermicide)
    • 100% commitment to abstinence
  • Unacceptable forms of contraception for women of childbearing potential
    • Oral contraception containing progestins only
    • IUD progesterone T
    • Female condom
    • Natural family planning (rhythm method) or breastfeeding
    • Fertility awareness
    • Withdrawal
    • Cervical shield
  • Willing to abstain from smoking
  • Willing to complete a daily pill diary

Exclusion Criteria

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Uncontrolled intercurrent illness including, but not limited to
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following prior therapies
    • Chemotherapy ≤ 4 weeks prior to registration
    • Mitomycin C/nitrosoureas ≤ 6 weeks prior to registration
    • Immunotherapy ≤ 4 weeks prior to registration
    • Biologic therapy ≤ 4 weeks prior to registration
    • Radiation therapy ≤ 4 weeks prior to registration
    • Radiation to > 25% of bone marrow
  • Failure to fully recover from acute, reversible effects of prior therapy regardless of interval since last treatment
  • New York Heart Association classification III or IV
  • Seizure disorder
  • Central nervous system (CNS) metastases if not stable for at least 2-3 months based on imaging, clinical assessment, and use of steroids, or seizure disorder
  • Pregnant
  • Nursing
  • Of childbearing potential and unwilling to employ adequate contraception until 12 months after last study drug dose
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Current therapy with a CYP3A4 inhibitor or inducer
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients receiving highly active antiretroviral therapy treatment
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in-situ of the cervix
    • If a history of prior malignancy, must not be receiving other specific treatment (other than hormonal therapy) for cancer
  • History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • More than 2 prior chemotherapy regimens for the current metastatic malignancy
    • Full dose chemotherapy used in conjunction with concurrent radiation therapy will be included as prior therapy
    • Prior hormonal therapy (e.g. leuprolide, aromatase inhibitors, tamoxifen) will be allowed and not included as a prior chemotherapy
  • Previous therapy with a hedgehog inhibitor

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions