Enzalutamide in Patients With Androgen Receptor Positive (AR+) Ovarian, Primary Peritoneal or Fallopian Tube Cancer and One, Two or Three Prior Therapies

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01974765
First received: October 25, 2013
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

This is a Phase II study. The purpose of this study is to find out what effects, good and/or bad enzalutamide has on the patient and the cancer. All patients who enter the study will be closely monitored for side-effects. If multiple patients develop significant side effects from enzalutamide, the study may be stopped early.

Enzalutamide is an androgen-receptor inhibitor, which means that it blocks the activity of the hormone testosterone. In ovarian, fallopian tube, and primary peritoneal cancers that express the androgen receptor, blocking the androgen-receptor may possibly slow or stop tumor growth. Enzalutamide has been studied in women with breast cancer, but this is the first study using enzalutamide for the treatment of patients with ovarian, primary peritoneal, or fallopian tube cancer.


Condition Intervention Phase
Advanced Epithelial Ovarian
Recurrent Epithelial Ovarian
Fallopian Tube
Primary Peritoneal Carcinoma.
Drug: Enzalutamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Enzalutamide in Patients With Androgen Receptor Positive (AR+) Ovarian, Primary Peritoneal or Fallopian Tube Cancer and One, Two or Three Prior Therapies

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • complete response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    by RECIST 1.1 criteria

  • partial response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    by RECIST 1.1 criteria


Secondary Outcome Measures:
  • adverse events [ Time Frame: every 2 weeks during the first cycle and every 4 weeks during subsequent cycles of treatment ] [ Designated as safety issue: Yes ]
    To determine the frequency and severity of adverse events as assessed by NCI CTCAE version 4.0.


Estimated Enrollment: 58
Study Start Date: November 2013
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide
All enrolled patients will be treated with enzalutamide 160 mg by mouth QD until progression of disease (POD), unacceptable toxicity or withdrawal from study. All treatments will be administered in the outpatient setting.
Drug: Enzalutamide
All enrolled patients will be treated with enzalutamide 160mg by mouth QD. Study drugs will be self-administered by patients. A cycle is 28 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Advanced or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Histologic documentation of the original primary tumor is required via the pathology report
  • AR expression ≥10% by IHC
  • Patients with the following histologic cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified
  • Measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. Each lesion must be ≥10mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20mm when measured by chest x-ray. Lymph nodes must be ≥ 15mm in short axis when measured by CT or MRI
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease
  • Patients may have received, but are not required to have received, one or two additional cytotoxic regimens for management of recurrent or persistent disease
  • Patients who have received only one prior cytotoxic regimen (platinum-based regimen management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
  • Patients are allowed to receive, but are not required to receive, non-cytotoxic therapy (such as bevacizumab) as part of their primary treatment regimen.
  • Patients are allowed to receive, but are not required to receive, non-cytotoxic therapy for management of recurrent or persistent disease
  • Must be ≥ 18 years of age
  • Karnofsky Performance Status (KPS) of ≥ 70%
  • Life expectancy of ≥ 12 weeks Women of child-bearing potential must have a negative pregnancy test within 14 days prior to commencement of study treatment
  • Women of child bearing potential must use an effective form of contraception during study and for at least 6 months after completion of study treatment
  • Recovery from effects of recent surgery, radiotherapy, or chemotherapy

    • At least 4 weeks out from their last dose of radiation therapy
    • At least 4 weeks post-op from any major surgical procedure
    • At least 3 weeks out from their last dose of chemotherapy and/or biologic/targeted therapy
  • No history of prior hormonal therapy for treatment of cancer within the past 3 years
  • Absence of any psychological, familial, sociological or geographic condition that would potentially hamper compliance with the study protocol
  • Prior use of or participation in a clinical trial evaluating and agent that either blocks androgen synthesis (e.g. abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the AR (e.g., bicalutamide, BMS-641988) (patients who are known to have only received placebo in these studies are eligible)
  • Laboratory Test Findings performed within 14 days prior to initiation of study drug showing:

Bone marrow function:

Absolute neutrophil count (ANC) ≥ 1,000/mcL Platelets ≥ 100,000/mcL Hemoglobin ≥ 8 g/dL o Renal function: Creatinine ≤ 1.5 x ULN

o Hepatic function: Bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN

  • Resolution of all acute toxic effects of prior therapy to NCI CTCAE (Version 4.0) Grade ≤ 1, with the exception of unresolved Grade 2 neuropathy and Grade 2 alopecia, which are allowed
  • Patients must be able to swallow tablets whole, without crushing

Exclusion Criteria:

  • A history of another invasive malignancy (other than non-melanoma skin cancer or curatively treated in situ carcinoma) with evidence of disease within the past 3 years
  • Use of a medication known to lower the seizure threshold within 28 days of first dose of study drug
  • Known brain metastasis
  • History of seizure
  • Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95mmHg) despite medical treatment. Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
  • Clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic event within the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline
  • Refractory nausea and vomiting, requirement for parenteral hydration and/or nutrition, drainage gastrostomy tube, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study drug absorption
  • Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01974765

Contacts
Contact: Rachel Grisham, MD 646-888-4653
Contact: Carol Aghajanian, MD 646-888-4217

Locations
United States, New Jersey
Memorial Sloan-Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States
Contact: Rachel Grisham, MD    646-888-4653      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Rachel Grisham, MD    646-888-4653      
Memorial Sloan-Kettering Cancer Center 1275 York Avenue Recruiting
New York, New York, United States, 10021
Contact: Rachel Grisham, MD    646-888-4653      
Contact: Carol Aghajanian, MD    646-888-4217      
Principal Investigator: Rachel Grisham, MD         
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Rachel Grisham, MD    646-888-4653      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Rachel Grisham, MD    646-888-4653      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Medivation, Inc.
Investigators
Principal Investigator: Rachel Grisham, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01974765     History of Changes
Other Study ID Numbers: 13-119
Study First Received: October 25, 2013
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Enzalutamide
Androgen Receptor Positive (AR+)
13-119

Additional relevant MeSH terms:
Carcinoma
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014