Clinical trial NCT00402662 (phase 2, status: terminated)
Conditions: metastatic melanoma
ICD codes: C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4
Drugs: everolimus, imatinib
SMILES: [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC, CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1
Reason stopped: 
    unexpected level of toxicity
  
Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed stage III unresectable or stage IV
             metastatic melanoma. Patients must have measurable disease as defined by RECIST
             criteria.

          -  Patients with up to 1 prior cytotoxic regimen for metastatic disease will be eligible.
             There will be no prior limitation on adjuvant therapies for stage II/III disease or
             for patients with stage IV disease treated after resection of all metastatic disease.
             There will be no prior limitation on biological or hormonal therapies (immune
             therapies, interferon, hypomethylating agents, histone deacetylase inhibitors, etc.),
             however, patients previously treated with mTOR inhibitors will be excluded. Prior
             treatment for metastatic disease is not required. Patients must have recovered from
             the acute toxicities of prior treatment. Chronic toxicities must have recovered to ≤
             grade 1. The minimum interval between prior treatment and first day of dosing on this
             trial is as follows: standard cytotoxic agents and radiation therapy, 21 days;
             mitomycin and nitrosoureas, 6 weeks; hormonal and immunotherapy agents, 2 weeks; minor
             surgery, 2 weeks, major surgery, 3 weeks; investigational agents 4-weeks.

          -  Age >18 years. Because no dosing or adverse event data are currently available on the
             use of everolimus in combination with imatinib in patients <18 years of age, children
             are excluded from this study, but will be eligible for future pediatric phase 1
             combination trials.

          -  ECOG performance status < 1.

          -  Life expectancy of greater than 3 months.

          -  Patients must have organ and marrow function as defined below:

          -  Leukocytes >3,000/μL; Absolute neutrophil count >1,500/ μL; platelets >100,000/ μL;
             Hemoglobin ≥ 9.0 gm/dL (may be transfused to this level); PT/PTT < 1.5x upper limit of
             normal; Total bilirubin ≤ 2.0 mg/dL;AST(SGOT)/ALT(SGPT) <3X institutional upper limit
             of normal; Creatinine ≤ 2.0 mg/dL or creatinine clearance >50 mL/min/1.73m2

          -  The effects of everolimus and imatinib on the developing human fetus are unknown. For
             this reason, women of child-bearing potential and men must agree to use adequate
             contraception (barrier method of birth control; abstinence) prior to study entry, for
             the duration of study participation and 3 months after stopping study drug. Should a
             woman (or the partner of a man participating in this trial) 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.

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents. Patients may not have
             received prior treatment for their cancer with an mTOR inhibitor.

          -  Patients with known brain metastases or leptomeningeal disease are 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. Patients with previously treated brain metastases, who no
             longer require steroids, and have no evidence of progression for at least 8 weeks
             following treatment of known brain metastases, are eligible.

          -  Baseline diastolic blood pressure > 95 mmHg. Blood pressure medications may be used to
             bring the diastolic pressure to levels acceptable for protocol enrollment.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular
             cardiac arrhythmia, myocardial infarction within the previous 6 months, dyspnea at
             rest, active GI bleeding or ulcer disease, diabetes mellitus, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  Pregnant women are excluded from this study because everolimus and imatinib are agents
             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 everolimus and imatinib, breastfeeding should be
             discontinued if the mother is treated on this protocol. These potential risks may also
             apply to other agents used in this study.

          -  Known HIV-positive patients, because of the potential for pharmacokinetic interactions
             with everolimus and imatinib, and because the potential immunosuppressive actions of
             everolimus may increase progression or infectious complications of HIV. Appropriate
             studies will be undertaken in HIV-positive patients when indicated.

          -  Patients receiving warfarin (see section 5.2), or chronic treatment with steroids or
             another immunosuppressive agent. In addition, patients requiring the following agents
             are excluded from the study, and must not take the agents while on the trial:
             ketoconazole, itraconazole, erythromycin, clarithromycin, dexamethasone, phenytoin,
             carbamazepine, rifampin, Phenobarbital, St. John's Wort, simvastatin, other HMG-CoA
             reductase inhibitors (if metabolized by CYP3A4), cyclosporine, pimozide,
             triazolo-benzodiazepines, dihydropyridine calcium channel blockers, and acetaminophen
             or acetaminophen containing products such as Percoset or Vicodin. Patients taking
             CYP3A4 interacting agents with narrow therapeutic windows will be excluded from the
             trial.

          -  Patient is < 5 years free of another primary malignancy except: if the other primary
             malignancy is not currently clinically significant nor requiring active intervention,
             or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in
             situ. Existence of any other malignant disease is not a allowed.