Abiraterone Acetate Plus LHRH Agonist and Abiraterone Acetate Plus LHRH Agonist and Enzalutamide

NCT01946165 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2013-0332NCI-2014-01041
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if adding the combination of abiraterone acetate and prednisone with or without enzalutamide to hormonal therapy can help to control prostate cancer when given before surgery. The safety of the drug combination will also be studied.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; High risk prostate cancer; Abiraterone acetate; Zytiga; Prednisone; Enzalutamide; MDV3100; XTANDI; Androgen ablation; LHRHa; Hormonal therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Pathologic Stage Less Than or Equal to ypT2N0

  The proportion of participants with pathologic stage less than or equal to ypT2N0 will be descriptively summarized and compared between the two treatment arms. The proportion will be calculated as the number of patients with less than or equal to ypT2N0 in each treatment arm divided by the total number of patients who underwent surgery in the same arm.

  For all participants who underwent surgery, from start of treatment until surgery is completed

Secondary Outcomes (1)

• Proportion of Participants With Positive Surgical Margins

  For both groups, tumor samples collected at baseline and during surgery.

Study Arms (2)

Abiraterone Acetate + Prednisone + Enzalutamide + LHRHa

EXPERIMENTAL

Patients receive abiraterone acetate (1,000 mg daily) plus prednisone (5mg once daily) in combination with enzalutamide (160 mg daily) and LHRHa. Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Drug: Abiraterone Acetate; Drug: Prednisone; Drug: Enzalutamide; Drug: LHRHa

Abiraterone Acetate + Prednisone + LHRHa

EXPERIMENTAL

Patients receive abiraterone acetate (1,000 mg daily) plus prednisone (5mg once daily) and LHRHa. Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Drug: Abiraterone Acetate; Drug: Prednisone; Drug: LHRHa

Interventions

Abiraterone Acetate DRUG

1,000 mg by mouth daily for each 28 day cycle.

Also known as: Zytiga

Abiraterone Acetate + Prednisone + Enzalutamide + LHRHa; Abiraterone Acetate + Prednisone + LHRHa

Prednisone DRUG

5 mg by mouth once daily for each 28 day cycle.

Abiraterone Acetate + Prednisone + Enzalutamide + LHRHa; Abiraterone Acetate + Prednisone + LHRHa

Enzalutamide DRUG

160 mg by mouth daily for each 28 day cycle.

Also known as: MDV3100, XTANDI

Abiraterone Acetate + Prednisone + Enzalutamide + LHRHa

LHRHa DRUG

Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Abiraterone Acetate + Prednisone + Enzalutamide + LHRHa; Abiraterone Acetate + Prednisone + LHRHa

Eligibility Criteria

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

You may qualify if:

• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Have signed an informed consent document indicating that the subjects understand the purpose of and procedures required for the study and are willing to participate in the study
• Written Authorization for Use and Release of Health and Research Study Information has been obtained.
• Male age \>/=18 years.
• Histologically or cytologically confirmed adenocarcinoma of the prostate with no histological variants (such as small cell, sarcomatoid, pure ductal cancer, transitional cell carcinoma).
• Pathology review at treating academic institution or member institution (Note: if patient's prostate biopsy was not read at the treating institution, it must be reviewed at the study site to confirm eligibility).
• At least three core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained at baseline). A prostate biopsy within 3 months from screening is allowed for entry requirements. Patients must have a Gleason score \> 5 (total).
• At least one of the following features: a) PSA \> 10 ng/ml; b) PSA velocity \> 2 ng/ml/year (defined as a rise in PSA of \> 2 ng/ml in the preceding 12 month period); c) Gleason score \>/= 7; d) Gleason score 6 if either PSA \>/= 10 ng/ml or PSA velocity \>/=2 ng/ml/year
• Serum testosterone \>200 ng/dL. For patients treated with up to 1 month of LHRH agonist, a testosterone measurement prior to the LHRH treatment will be used to determine eligibility, and must have been \> 200 ng/dL.
• Urologist must agree that patient is suitable for prostatectomy.
• No evidence of metastatic disease as determined by imaging procedures.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Hemoglobin \>/= 10.0 g/dL independent of transfusion.
• Platelet count \>/=100,000/µL.
• Patients should have adequate bone marrow function defined as an absolute peripheral neutrophil count (ANC) \>/= 1,500.

You may not qualify if:

• Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection.
• Chronically uncontrolled hypertension, defined conventionally as consistent systolic pressures above 140 or diastolic pressures above 90 despite anti-hypertensive therapy. Note that this is NOT a criterion related to particular BP results at the time of assessment for eligibility, nor does it apply to acute BP excursions that are related to iatrogenic causes, acute pain or other transient, reversible causes.
• Requirement for corticosteroids greater than the equivalent of 5 mg of prednisone daily.
• Poorly controlled diabetes defined by Hemoglobin A1C \> 7.0 at screening.
• Active or symptomatic viral hepatitis or chronic liver disease.
• History of pituitary or adrenal dysfunction.
• Clinically significant cardiovascular disease including: a) Myocardial infarction within 6 months of Screening visit; b) Uncontrolled angina within 3 months of Screening visit; c) Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the Screening visit results in a left ventricular ejection fraction that is \>/= 50%; d) History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes); e) Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening Electrocardiogram (ECG) \> 470 msec; f) History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
• Other malignancy, except non-melanoma skin cancer, that is active or has a \>/= 30% probability of recurrence within 12 months.
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or LHRH agonists/antagonists (\*Note: LHRH allowed if begun within 1 month of Day 1). Patients having previous or current antiandrogen treatment of greater than 4 weeks in duration prior to Cycle 1 Day 1 are eligible with appropriate washout.
• Prior systemic treatment with an azole drug within four weeks of Cycle 1 Day1.
• Current enrollment in an investigational drug or device study or participation in such a study within 30 days of Cycle 1 Day 1.
• Allergies, hypersensitivity, or intolerance to prednisone, LHRH analog or excipients of prednisone LHRH analog, and abiraterone acetate and enzalutamide.
• Previous use of abiraterone acetate or other investigational CYP17 inhibitor (e.g., TAK-700).
• Previous investigational antiandrogens (e.g., Enzalutamide, BMS-641988).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Janssen Services, LLC: collaborator
• Medivation, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Han H, Wang Y, Curto J, Gurrapu S, Laudato S, Rumandla A, Chakraborty G, Wang X, Chen H, Jiang Y, Kumar D, Caggiano EG, Capogiri M, Zhang B, Ji Y, Maity SN, Hu M, Bai S, Aparicio AM, Efstathiou E, Logothetis CJ, Navin N, Navone NM, Chen Y, Giancotti FG. Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis. Cell Rep. 2022 Apr 5;39(1):110595. doi: 10.1016/j.celrep.2022.110595.

  PMID: 35385726 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Christopher J. Logothetis M.D. / Genitourinary Medical Oncology
• Organization: UT MD Anderson Cancer Center

clogothe@mdanderson.org

713-792-2830

Study Officials

• Christopher Logothetis, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 16, 2013
• First Posted: September 19, 2013
• Study Start: October 31, 2013
• Primary Completion: July 28, 2017
• Study Completion: July 28, 2017
• Last Updated: December 6, 2019
• Results First Posted: December 6, 2019

Record last verified: 2019-11

Locations

US (1)