A Study of ENMD-2076 in Ovarian Clear Cell Cancers
Condition: Ovarian Clear Cell Carcinoma
MeSH terms: Carcinoma; Adenomyoepithelioma; Adenocarcinoma, Clear Cell
Intervention: ENMD-2076
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ovarian; cancer; clear cell; ENMD-2076; oral; capsule

Summary:

      This is a phase 2 study to see how useful, safe, and tolerable an investigational drug called
      ENMD-2076 is in treating patients with ovarian clear cell carcinomas.

      ENMD-2076 is an oral drug that works by blocking certain enzymes called Aurora A and tyrosine
      kinase from working. These enzymes are needed for cells to divide including cancer cells.
      ENMD-2076 also works by stopping the growth of new blood vessels which would provide the
      tumor with nutrients for it to grow. It is believed that by blocking Aurora A and tyrosine
      kinase enzymes from working and stopping new blood vessels from growing, the tumors may stop
      growing or shrink.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have histologically documented diagnosis of ovarian clear cell carcinoma.

          -  Any number of prior chemotherapy regimens will be allowed but must include 1 line of
             platinum based therapy, and may include chemotherapy, biologics or other targeted
             therapies (except for Aurora A targeted therapies).

          -  Meet RECIST criteria (version 1.1) within 28 days of start of treatment by having
             measurable disease defined as one or more lesions that can be accurately measured in
             one or more dimensions. Areas of previous radiation may not serve as measurable
             disease unless there is evidence of progression post radiation.

          -  At time of registration, if the patient has had previous treatment it must have been
             at least 4 weeks since major surgery or radiation therapy; four weeks from any other
             previous anti-cancer therapy including biologics. Patients must have recovered from
             their treatment-related events with the exception of alopecia.

          -  Are ≥18 years of age

          -  Have clinically acceptable laboratory screening results within certain limits
             specified below:

               -  AST and ALT ≤ 2.5 times upper limit of normal (ULN) or less than or equal to 5
                  times ULN if liver metastases are present

               -  Total bilirubin ≤ 1.5 x ULN

               -  Creatinine ≤ 1.5 x UL

               -  Absolute neutrophil count ≥ 1500 cells/mm

               -  Platelets ≥ 150,000/mm3

               -  Hemoglobin ≥ 9.0 g/dl

          -  Have an ECOG performance status of ≤ 2

          -  Women of child-producing potential must agree to use effective contraceptive methods
             prior to study entry, during study participation, and for at least 30 days after the
             last administration of study medication. A serum pregnancy test within 72 hours prior
             to the initiation of therapy will be required for women of childbearing potential.

          -  Have the ability to understand the requirements of the study, provide written informed
             consent, abide by the study restrictions, and agree to return for the required
             assessments.

          -  Able to tolerate oral medication.

        Exclusion Criteria:

          -  Women who are pregnant or nursing

          -  Have active, acute, or chronic clinically significant infections or bleeding.

          -  Have uncontrolled hypertension (systolic blood pressure greater than 150mmHg or
             diastolic blood pressure greater than 100mmHg); or history of congestive heart failure
             (equal to or greater than Grade 2).

          -  Have active angina pectoris, stroke, previous myocardial infarction within the past 12
             months and not clinically stable, or any other pre-existing uncontrolled
             cardiovascular condition.

          -  Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater
             than 470 msec.

          -  Have additional uncontrolled serious medical or psychiatric illness.

          -  Require therapeutic doses of anti-coagulation with warfarin or other coumarin
             derivatives. However, treatment with low molecular weight heparin (LMWH) is allowed.

          -  Known CNS metastases

          -  Have any medical condition that would impair the administration of oral agents
             including recurrent bowel obstructions, inflammatory bowel disease or uncontrolled
             nausea, vomiting or diarrhea

          -  Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a
             spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of
             nephrotic syndrome

          -  Have an active or history of additional malignancy which in the opinion of the study
             doctor would make assessment of outcome difficult.

          -  Require treatment with drugs known to be potent inducers or inhibitors of CYP3A4 at
             the time of registration