Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma
Condition: Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma
MeSH terms: Melanoma; Hutchinson's Melanotic Freckle; Lentigo
Intervention: gamma-secretase/Notch signalling pathway inhibitor RO4929097; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: 2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well gamma-secretase/Notch signalling pathway inhibitor
      RO4929097 works in treating patients with stage IV melanoma. Gamma-secretase/Notch signalling
      pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed melanoma of cutaneous or unknown origin
             (ocular primary and mucosal primary excluded); patients must have Stage IV disease

          -  All patients must undergo a computed tomography (CT) or magnetic resonance imaging
             (MRI) of the brain within 42 days prior to registration that is negative for brain
             metastases; patients with a history of brain metastases are ineligible

          -  Patients must have measurable disease; all measurable lesions must be assessed (by
             physical examination, CT, or MRI scan) within 28 days prior to registration; tests to
             assess non-measurable disease must be performed within 42 days prior to registration;
             all disease must be assessed and documented on the Baseline Tumor Assessment Form
             (Response Evaluation Criteria In Solid Tumors [RECIST] 1.1); the CT from a combined
             positron emission tomography (PET)/CT must not be used to document measurable disease
             unless it is of diagnostic quality

          -  Sites must offer all patients participation in translational medicine studies and
             banking of paraffin embedded tissue and whole blood

          -  Patients must not have received any prior systemic therapy for Stage IV disease except
             for noncytotoxic biologic agents (e.g., vaccines, cytokines, cell therapies that do
             not require cytotoxic agents); patients may have received prior treatment with up to
             two prior biological therapies - no cytotoxics or kinase inhibitors - for advanced
             disease

          -  Patients may have had prior adjuvant immunotherapy with biological response modifiers
             (examples include but are not limited to interferon, vaccines, GM-CSF, and CTLA-4
             blocking antibodies); prior adjuvant immunotherapy must have been completed at least
             28 days prior to registration

          -  Adjuvant therapy containing cytotoxic agents is allowed if completed >= 180 days prior
             to registration

          -  Patients may have received prior radiation therapy; any side effects the patients had
             due to prior radiation therapy must have resolved to =< Grade 1 prior to registration;
             prior radiation therapy must have completed at least 28 days prior to registration

          -  Patients must have Zubrod performance status of 0-1

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin =< institutional upper limit of normal (IULN)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x IULN

          -  Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/min

          -  Patients must have the following serum electrolytes within the institutional ranges of
             normal: potassium, sodium, magnesium, phosphorous, chloride and calcium (corrected for
             serum albumin); these tests must be performed within 28 days prior to registration;
             patient must not require parenteral replacement therapy

          -  Patients must not have a history of allergic reaction attributed to compounds of
             similar chemical or biologic composition to RO4929097

          -  Patients must be able to swallow tablets

          -  Patients must not have malabsorption syndrome or other condition that would interfere
             with intestinal absorption of the agent

          -  Patients taking medications with narrow therapeutic indices that are metabolized by
             cytochrome P450 (CYP450), including warfarin sodium (Coumadin), are ineligible

          -  Patients must not be taking strong inducers or strong inhibitors of CYP3A4 at the time
             of registration

          -  Patients must not be known to be serologically positive for Hepatitis A, B, or C, or
             have a history of liver disease, other forms of hepatitis, or cirrhosis

          -  Patients must have an ECG within 28 days prior to registration. Patients must not have
             a QTcF > 450 msec (males) or QTcF > 470 msec (females)

          -  Patients must not have symptomatic congestive heart failure or unstable angina
             pectoris

          -  Patients with a history of torsades de pointes or any significant cardiac arrhythmia
             (except asymptomatic unifocal ventricular premature beats or supraventricular
             tachycardia easily controlled with oral medications) are excluded; any patient
             requiring or expected to require antiarrhythmics or other therapy known to prolong QTc
             is also excluded

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             Stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease free for five years

          -  Women of childbearing potential must have a negative pregnancy test within 14 days
             prior to registration (the type of pregnancy test used is at the discretion of the
             registering institution); female patients of childbearing potential include the
             following:

               -  Patients with regular menses

               -  Patients, after menarche with amenorrhea, irregular cycles, or using a
                  contraceptive method that precludes withdrawal bleeding

               -  Women who have had tubal ligation

          -  Women must not be nursing due to possible harm to a nursing infant from the treatment
             regimen

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines

          -  At the time of patient registration, the treating institution's name and ID number
             must be provided to the Data Operations Center in Seattle in order to ensure that the
             current (within 365 days) date of institutional review board approval for this study
             has been entered into the data base