Clinical Trials /

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

NCT01974765

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 13-119
  • NCT ID: NCT01974765

Conditions

  • Advanced Epithelial Ovarian
  • Recurrent Epithelial Ovarian
  • Fallopian Tube
  • Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
EnzalutamideEnzalutamide

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.

Trial Arms

NameTypeDescriptionInterventions
EnzalutamideExperimentalAfter signing a screening consent, patients archival tissue will be evaluated for degree of AR positivity by AR staining. Patients with no archival tissue available will undergo a biopsy (using the modality deemed most appropriate by the patient's physician) for collection of tumor tissue for AR positivity by IHC. Only AR+ patients, defined as ≥5 % positivity by IHC, will be included. All IHC testing will be performed in the MSKCC Clinical CLIA approved laboratory. 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.
  • Enzalutamide

Eligibility 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 ≥5% by IHC. In cases where multiple blocks are available staining will
             be performed on unstained slides from 3 separate blocks. If ≥ 5% AR tumor staining is
             seen on ≥ 1 slide the tumor will be considered to be AR+.

          -  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 prior hormonal therapy for treatment of cancer within the past 21 days

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:complete response
Time Frame:6 months
Safety Issue:
Description:by RECIST 1.1 criteria

Secondary Outcome Measures

Measure:adverse events
Time Frame:every 2 weeks during the first cycle and every 4 weeks during subsequent cycles of treatment
Safety Issue:
Description:To determine the frequency and severity of adverse events as assessed by NCI CTCAE version 4.0.
Measure:AR expression levels on tissue
Time Frame:2 years
Safety Issue:
Description:will be determined using standard immunohistochemistry methodology on all tissue and reported as percent tumor cells with nuclear

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Enzalutamide
  • Androgen Receptor Positive (AR+)
  • 13-119

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