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About
This phase II trial studies how well enzalutamide, carboplatin, and paclitaxel work in treating patients with endometrioid endometrial cancer that is stage III-IV or has come back. Androgens can cause the growth of endometrioid endometrial cancer. Antihormone therapy, such as enzalutamide may lessen the amount of androgen made by the body. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving enzalutamide, carboplatin, and paclitaxel may work better in treating patients with endometrioid endometrial cancer.
Full description
PRIMARY OBJECTIVES:
I. To determine the clinical activity of combination enzalutamide, carboplatin and paclitaxel represented as:
Ia. Objective tumor response (complete response [CR] + partial response [PR]). Ib. The proportion of patients who survive progression-free for at least 6 months after initiating therapy.
II. To quantify protein and phosphoprotein expression of androgen receptor (AR) and AR-response genes following enzalutamide treatment in match-paired pre and post treatment tumor biopsies.
III. To determine the safety and feasibility of daily enzalutamide given in combination with carboplatin and paclitaxel in women with advanced stage or recurrent endometrial cancer.
SECONDARY OBJECTIVES:
I. Determine median response duration. II. Estimate progression free survival and overall survival. III. Evaluate for presence of pharmacokinetic interaction between enzalutamide and paclitaxel.
EXPLORATORY OBJECTIVES:
I. Correlate molecular results, including AR receptor expression and activation, to clinical endpoints.
II. Identify potential agents to synergize with enzalutamide based on pathways activated after enzalutamide treatment.
OUTLINE:
Patients receive enzalutamide orally (PO) once daily (QD) alone on days 1-28. Patients then receive enzalutamide PO QD on days 1-21, paclitaxel intravenously (IV) over 3 hours on day 1, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6-9 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 1 year.
Enrollment
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Inclusion criteria
Exclusion criteria
Patients who have isolated recurrences (vaginal, pelvic, or paraaortic) that are amenable to potentially curative treatment with radiation therapy or surgery
Patients with the following histologies of endometrial cancer are not eligible for enrollment: papillary serous adenocarcinoma, clear cell carcinoma, adenosquamous carcinoma, mucinous adenocarcinoma, carcinosarcoma, sarcoma
Prior Therapy:
Patients who have previously received enzalutamide; patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy
Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (CTCAE v4.03 grade 2 or greater, excluding alopecia) due to agents administered more than 4 weeks earlier
Patients may not receive any other anti-neoplastic or investigational agents within 3 weeks of study enrollment; patients may not be receiving any other investigational agents during treatment on protocol
Patients may not receive strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors, CYP2C8 inducers, or cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers; in addition, patients should not receive drugs that are metabolized by CYP3A4 or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9)
Patients who are pregnant or nursing; women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Patient had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery
Patients may not have a history of other malignancies except for basal cell or squamous cell skin cancer, in situ cervical cancer, unless they have been disease-free for at least five years
Patients with predisposing factors for seizure including history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastasis, and brain arteriovenous malformation
Patient with history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to enzalutamide, carboplatin, or paclitaxel
Patients may not have symptomatic, uncontrolled spinal cord compression and/or brain metastases; a scan to confirm absence of brain metastasis is not required; patients can receive a stable dose of corticosteroids before/ during study if these were started at least 28 days prior to entry
As judged by the investigator, any evidence of severe or uncontrolled systemic diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease], uncontrolled chronic renal diseases [glomerulonephritis, nephritic syndrome, Fanconi syndrome or renal tubular acidosis]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension (blood pressure >= 160/90), active bleeding diatheses or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus; screening for chronic conditions is not required
As judged by the investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
Primary purpose
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53 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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