Enzalutamide, Carboplatin, and Paclitaxel in Treating Patients With Stage III-IV or Recurrent Endometrioid Endometrial Cancer

NCT02684227 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2015-0723NCI-2016-00562
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Recurrent Endometrial Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage III Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IV Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

Outcome Measures

Primary Outcomes (3)

• Clinical Activity of Combination Enzalutamide, Carboplatin and Paclitaxel Represented as Objective Tumor Response (Complete Response (CR) + Partial Response (PR)).

  No dose-limiting toxicities were observed during the safety lead-in. Objective tumor response (complete response (CR) + partial response (PR)).

  up to 6.4 years

• 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

  We will tabulate the adverse events by grade and relationship to study drug. Participants had at least 1 treatment-related adverse event.

  up to 6.4 years

• Median Duration of Progression-free Survival

  up to 6.4 years

Secondary Outcomes (1)

• Overall Survival

  up to 6.4 years

Study Arms (1)

Treatment (enzalutamide, paclitaxel, carboplatin)

EXPERIMENTAL

Patients receive enzalutamide PO QD alone on days 1-28. Patients then receive enzalutamide PO QD on days 1-21, paclitaxel 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.

Drug: Carboplatin; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (enzalutamide, paclitaxel, carboplatin)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (enzalutamide, paclitaxel, carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (enzalutamide, paclitaxel, carboplatin)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (enzalutamide, paclitaxel, carboplatin)

Pharmacological Study OTHER

Correlative studies

Treatment (enzalutamide, paclitaxel, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of advanced stage (stage III or IV) or recurrent endometrioid endometrial cancer
• Measurable disease (at least one measurable lesion) IS required; a measurable lesion is one that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \> 10 mm when measured by computed tomography (CT) scan, magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or \> 20 mm when measured by chest x-ray; lymph nodes must be \> 15 mm in short axis when measured by CT or MRI
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by Response Evaluation Criteria in Solid Tumors (RECIST); tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• Patient with an Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Life expectancy of greater than 3 months in the opinion of the principal investigator
• Recovery from effects of recent surgery, radiotherapy, or chemotherapy
• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration
• PRIOR THERAPY: Patients should have had NO prior chemotherapy agents for advanced or recurrent endometrial cancer; prior chemotherapy administration in conjunction with primary radiation therapy as a radiosensitizer would NOT exclude a patient from participation in this trial
• Absolute neutrophil count (ANC) \>= 1,500/mcl, equivalent to Common Terminology Criteria (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4.03) grade 1
• Platelets \>= 100,000/mcl
• Calculated creatinine clearance (Cockcroft-Gault formula) \> 50 ml/min OR 24-hour urine creatinine clearance \> 50 ml/min
• Bilirubin =\< 1.5 x upper limit of normal (ULN) (CTCAE v4.03 grade 1; in patients with known Gilbert syndrome, a total bilirubin =\< 3.0 x ULN, with direct bilirubin =\< 1.5 x ULN)
• Aspartate aminotransferase (AST) and alkaline phosphatase =\< 2.5 x ULN (CTCAE v4.03 grade 1; AST and alanine aminotransferase \[ALT\] =\< 3 x ULN \[or =\< 5.0 x ULN if hepatic metastases are present\])

You may not qualify if:

• 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:
• Prior Chemotherapy: Patients who have had a prior chemotherapy regimen for advanced or metastatic disease are excluded
• Prior Radiation Therapy: Patients may have received prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy, alone or with chemotherapy as a radiation sensitizer; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy, the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided at registration
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Woman's Hospital of Texas

Houston, Texas, 77054, United States

Location

MD Anderson in Katy

Houston, Texas, 77094, United States

Location

MD Anderson League City

Nassau Bay, Texas, 77058, United States

Location

MD Anderson in Sugar Land

Sugar Land, Texas, 77478, United States

Location

MD Anderson in The Woodlands

The Woodlands, Texas, 77384, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Carboplatin; enzalutamide; Paclitaxel; Taxes

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Shannon Westin, MD
• Organization: MD Anderson Cancer Center

swestin@mdanderson.org

713-794-4314

Study Officials

• Shannon N Westin, M D

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 17, 2016
• Study Start: August 24, 2016
• Primary Completion: September 27, 2023
• Study Completion: September 27, 2023
• Last Updated: March 19, 2025
• Results First Posted: March 19, 2025

Record last verified: 2025-02

Locations

US (6)