A Study of ENMD-2076 in Ovarian Clear Cell Cancers
Primary Purpose
Ovarian Clear Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
ENMD-2076
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Clear Cell Carcinoma focused on measuring ovarian, cancer, clear cell, ENMD-2076, oral, capsule
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
Sites / Locations
- Tom Baker Cancer Centre
- Cross Cancer Institute
- British Columbia Cancer Agency
- London Regional Cancer Program
- Ottawa Regional Cancer Centre
- Princess Margaret Cancer Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ENMD-2076
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Complete or Partial Response Rate
Percentage of patients with complete or partial response as per RECIST 1.1 criteria.
Secondary Outcome Measures
Time to Disease Progression
Length of time until disease progression in patients treated with ENMD-2076
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.
Full Information
NCT ID
NCT01914510
First Posted
July 11, 2013
Last Updated
December 12, 2019
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT01914510
Brief Title
A Study of ENMD-2076 in Ovarian Clear Cell Cancers
Official Title
Phase II Study of Oral ENMD-2076 Administered to Patients With Ovarian Clear Cell Carcinomas
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Clear Cell Carcinoma
Keywords
ovarian, cancer, clear cell, ENMD-2076, oral, capsule
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ENMD-2076
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ENMD-2076
Primary Outcome Measure Information:
Title
Six Month Progression Free Survival Rate
Description
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.
Time Frame
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.
Title
Complete or Partial Response Rate
Description
Percentage of patients with complete or partial response as per RECIST 1.1 criteria.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Time to Disease Progression
Description
Length of time until disease progression in patients treated with ENMD-2076
Time Frame
2 years
Title
Levels of Certain Proteins and Gene Expression Compared to Patient Outcome Following Treatment
Description
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.
Time Frame
2 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Oza, M.D.
Organizational Affiliation
Princess Margaret Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
British Columbia Cancer Agency
City
Vancouver
State/Province
Alberta
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
London Regional Cancer Program
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Ottawa Regional Cancer Centre
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
A Study of ENMD-2076 in Ovarian Clear Cell Cancers
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