A Study of ENMD-2076 in Ovarian Clear Cell Cancers

Study Overview
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Brief Summary
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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.

Detailed Description
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During the study, participants will be asked to take ENMD-2076 once a day, everyday. Every 28 days will be called a cycle. While receiving the study drug, participants will be asked to visit the clinic for tests and procedures. During Cycle 1, participants will be asked to visit the clinic about once a week and during Cycle 2 and future cycles, participants will be asked to visit the clinic on days 1 and 15. As a part of the study, tumor tissue (archival and fresh tumor biopsy) will be taken for biomarker research. When participants stop the study drug, they will be asked to have an end of study drug visit.

Official Title
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Phase II Study of Oral ENMD-2076 Administered to Patients With Ovarian Clear Cell Carcinomas

Conditions
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Ovarian Clear Cell Carcinoma

Intervention / Treatment
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* Drug: ENMD-2076


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ENMD-2076<br>ENMD-2067 will be taken orally at a dose of 275 mg, once a day, everyday. Patients with a body surface area of less than 1.65 m2 will receive a starting dose of 250 mg, once a day, everyday. | Drug: ENMD-2076<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six Month Progression Free Survival Rate | Progression Free Survival (PFS) is defined as the time from first day of treatment to the first observation of disease progression or death due to any cause or last follow up. PFS will be censored for patients who are alive and free of progression at time of last follow-up. | Response will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. Progression free survival is the time from the first day of treatment to the first observation of disease progression or Death/last F/U. | 
| Complete or Partial Response Rate | Percentage of patients with complete or partial response as per RECIST 1.1 criteria. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Length of time until disease progression in patients treated with ENMD-2076 | 2 years | 
| Levels of Certain Proteins and Gene Expression Compared to Patient Outcome Following Treatment | Association of somatic mutations in PIK3CA, ARID1A and PTEN mutation status, and ARID1A and PTEN expression assessed in archival samples and tumour biopsies with tumour response and patient outcome following treatment with ENMD 2076. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ENMD-2076, ovarian, cancer, clear cell, oral, capsule