We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 5 of 104 for:    mdv3100 | Recruiting, Not yet recruiting, Available Studies

Enzalutamide in Combination With Carboplatin and Paclitaxel in Endometrial Cancer

This study is currently recruiting participants.
Verified October 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02684227
First Posted: February 17, 2016
Last Update Posted: October 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Astellas Pharma Inc
Medivation, Inc.
National Comprehensive Cancer Network
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

This clinical research study has two parts: a safety lead-in and Phase 2.

The goal of the safety lead-in is to find the highest tolerable dose of enzalutamide in combination with carboplatin and paclitaxel that can be given to patients with recurrent or advanced endometrial cancer.

The goal of Phase 2 of this study is to learn if the study drug combination can help to control recurrent or advanced endometrial cancer.

The safety of the drug combination will be studied in both parts of the study.

This is an investigational study. Enzalutamide is FDA approved for the treatment of certain types of prostate cancer. Paclitaxel and carboplatin are FDA approved for the treatment of ovarian cancer. The use of the combination of these 3 drugs to treat endometrial cancer is investigational.

Up to 69 participants will be enrolled in this study. All will take part at MD Anderson.


Condition Intervention Phase
Endometrial Cancer Drug: Enzalutamide Drug: Carboplatin Drug: Paclitaxel Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study With a Limited Safety Lead-In of Enzalutamide in Combination With Carboplatin and Paclitaxel in Advanced Stage or Recurrent Endometrioid Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Enzalutamide, in Combination with Paclitaxel and Carboplatin in Previously Untreated Participants with Advanced and Recurrent Endometrioid Endometrial Cancer [ Time Frame: 21 days ]
    MTD determined if 2 or fewer participants out of 6 experience dose limiting toxicities (DLTs), then the regimen deemed safe for administration in the phase II study.


Secondary Outcome Measures:
  • Objective Tumor Response of Enzalutamide, in Combination with Paclitaxel and Carboplatin in Previously Untreated Participants with Advanced and Recurrent Endometrioid Endometrial Cancer [ Time Frame: 12 weeks ]
    Objective tumor response is (complete response (CR) + partial response (PR)). Response evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).


Estimated Enrollment: 69
Actual Study Start Date: August 2016
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: Enzalutamide, Carboplatin + Paclitaxel
Safety Lead-in Phase (Part A): Combination of Enzalutamide (160 mg Daily Orally) & standard intravenous (IV) Carboplatin (AUC= 5) and Paclitaxel (175 mg/m^2) on Day 1 every 21 day cycle for 6-9 cycles.
Drug: Enzalutamide

Safety Lead-in Phase (Part A) Starting Dose: 160 mg by mouth daily of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Enzalutamide taken every day by itself during the first cycle (called Cycle 0).

Other Names:
  • MDV3100
  • XTANDI
Drug: Carboplatin

Safety Lead-in Phase (Part A) Starting Dose: Area under curve (AUC)= 5 by vein on Day 1 of Cycles 1 - 9 of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Carboplatin given by vein on Day 1 of Cycles 1 - 9.

Other Name: Paraplatin
Drug: Paclitaxel

Safety Lead-in Phase (Part A) Starting Dose: 175 mg/m2 by vein on Day 1 of Cycles 1 - 9 of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Paclitaxel given by vein on Day 1 of Cycles 1 - 9.

Other Name: Taxol
Experimental: Part B: Enzalutamide, Carboplatin + Paclitaxel
Phase II (Part B): Induction treatment single agent Enzalutamide at dose found in Part A daily orally for 28 days, then initiated on combination therapy of enzalutamide, paclitaxel, and carboplatin at dose levels for each drug as found in Part A, on day 1 every 21 days for 6-9 cycles.
Drug: Enzalutamide

Safety Lead-in Phase (Part A) Starting Dose: 160 mg by mouth daily of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Enzalutamide taken every day by itself during the first cycle (called Cycle 0).

Other Names:
  • MDV3100
  • XTANDI
Drug: Carboplatin

Safety Lead-in Phase (Part A) Starting Dose: Area under curve (AUC)= 5 by vein on Day 1 of Cycles 1 - 9 of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Carboplatin given by vein on Day 1 of Cycles 1 - 9.

Other Name: Paraplatin
Drug: Paclitaxel

Safety Lead-in Phase (Part A) Starting Dose: 175 mg/m2 by vein on Day 1 of Cycles 1 - 9 of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Paclitaxel given by vein on Day 1 of Cycles 1 - 9.

Other Name: Taxol

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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 CT scan, 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.
  3. Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by 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.
  4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status </= 1.
  5. Life expectancy of greater than 3 months in the opinion of the principal investigator.
  6. Recovery from effects of recent surgery, radiotherapy, or chemotherapy.
  7. Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI).
  8. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration.
  9. Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration.
  10. 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.
  11. Patients must have adequate: (1) Bone marrow function: Absolute neutrophil count (ANC) >/= 1,500/mcl, equivalent to Common Terminology Criteria (CTCAE v4.03) grade 1; Platelets >/= 100,000/mcl; (2) Renal function: calculated creatinine clearance (Cockcroft-Gault formula) > 50 ml/min OR 24-hour urine creatinine clearance > 50 ml/min; (3) Hepatic function: Bilirubin </= 1.5 x 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). AST and alkaline phosphatase </= 2.5 x ULN (CTCAE v4.03 grade 1; AST and ALT </= 3 x ULN (or </= 5.0 x ULN if hepatic metastases are present); (4) Neurologic function: Neuropathy (sensory and motor) </= CTCAE v4.03 grade 1; [Continued in Criterion 12]
  12. [Continued from Criterion 11] (5) PT such that international normalized ratio (INR) is </= 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a PTT </= 1.5 times the institutional upper limit of normal. Patients receiving low molecular weight heparin for the prevention or treatment of venous thromboembolic disease are eligible if considered clinically stable on their regimen.
  13. Patients must have signed an approved informed consent.
  14. Age >/=18 years. Because no dosing or adverse event data are currently available on the use of enzalutamide in combination with carboplatin and paclitaxel in patients <18 years of age, children are excluded from this study.
  15. The effects of enzalutamide on the developing human fetus are unknown. For this reason and because therapeutic agents used in this trial may be teratogenic, women of child-bearing potential and their partners 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. Women of child-bearing potential (intact uterus) should have a negative serum pregnancy test. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Patients must be able to swallow whole tablets.
  16. With the exception of alopecia, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE v4 Grade 1 at the time of starting study treatment.
  17. Patients on the Phase II portion only must be willing to undergo pre- and post-treatment biopsies and have at least one lesion amenable to biopsy.

Exclusion Criteria:

  1. Patients who have isolated recurrences (vaginal, pelvic, or paraaortic) that are amenable to potentially curative treatment with radiation therapy or surgery.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Patients may not receive strong CYP2C8 inhibitors, CYP2C8 inducers, or CYP3A4 inducers. In addition, patients should not receive drugs that are metabolized by CYP3A4 or CYP2C9.
  8. Patients who are pregnant or nursing. The effects of enzalutamide on the developing human fetus are unknown. For this reason 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.
  9. Patient had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery.
  10. 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.
  11. 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.
  12. Patient with history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to enzalutamide, carboplatin, or paclitaxel.
  13. 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.
  14. 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.
  15. 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02684227


Contacts
Contact: Shannon Westin, MD 713-794-4314

Locations
United States, Texas
MD Anderson Cancer Center - Memorial City Regional Care Center Recruiting
Houston, Texas, United States, 77024
Contact: Appointments    713-358-5300      
Principal Investigator: Nicole Fleming, MD         
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: MD Anderson Health Information Specialist    877-632-6789      
The Woman's Hospital of Houston Recruiting
Houston, Texas, United States, 77054
MD Anderson Cancer Center - Katy Regional Care Center Recruiting
Houston, Texas, United States, 77094
Contact: Appointments    713-745-9940      
Principal Investigator: Nicole Fleming, MD         
MD Anderson Cancer Center - Bay Area Regional Care Center Recruiting
Nassau Bay, Texas, United States, 77058
Contact: Appointments    713-745-9940      
Principal Investigator: Nicole Fleming, MD         
MD Anderson Cancer Center - Sugar Land Regional Care Center Recruiting
Sugar Land, Texas, United States, 77478
Contact: Appointments    713-745-9940      
Principal Investigator: Nicole Fleming, MD         
MD Anderson Cancer Center - The Woodlands Recruiting
The Woodlands, Texas, United States, 77384
Contact: Appointments    713-745-9940      
Principal Investigator: Nicole Fleming, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Astellas Pharma Inc
Medivation, Inc.
National Comprehensive Cancer Network
Investigators
Principal Investigator: Shannon Westin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02684227     History of Changes
Other Study ID Numbers: 2015-0723
NCI-2016-00562 ( Registry Identifier: NCI CTRP )
First Submitted: February 12, 2016
First Posted: February 17, 2016
Last Update Posted: October 31, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Endometrial cancer
Advanced Stage Endometrioid Endometrial Cancer
Recurrent Endometrioid Endometrial Cancer
Enzalutamide
MDV3100
XTANDI
Carboplatin
Paclitaxel
Taxol

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action