Maximal Androgen Depletion Followed by Randomization of Maximal Androgen Ablation With Molecular Targeted Therapies

NCT01254864 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2010-0070NCI-2011-00267
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

You are being asked to take part in this study because you have prostate cancer that has spread to other parts of the body. This is an investigational study. Prednisone is FDA-approved and commercially available. Abiraterone acetate is FDA-approved and commercially available, but is still being researched. Sunitinib malate is FDA-approved for the treatment of gastrointestinal tumors and renal cell carcinoma, and dasatinib is FDA approved and commercially available for certain types of leukemia. The use of these drugs in prostate cancer and in combination with abiraterone acetate and prednisone is investigational. Up to 180 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Conditions

Prostate Cancer

Keywords

Castrate resistant prostate cancer; Adenocarcinoma of the prostate; Sunitinib Malate; SUO11248; Sutent; BMS-354825; Sprycel

Outcome Measures

Primary Outcomes (1)

• Time to Treatment Failure (TTF)

  Time to treatment failure (TTF), defined as time from randomization (AP+S or AP+D) to progression per PCWG2 criteria or death.

  Up to 11 months

Study Arms (3)

Abiraterone Acetate + Prednisone (AP)

EXPERIMENTAL

Abiraterone Acetate at 1000 mg orally each day, given in combination with 5 mg of Prednisone orally twice daily.

Drug: Abiraterone Acetate; Drug: Prednisone

Group 1: AP + Sunitinib

EXPERIMENTAL

AP (Abiraterone Acetate + Prednisone) Plus Sunitinib; Randomized from AP group to receive Sunitinib if disease worsens. Assignment to crossover group AP + Dasatinib with further disease progression.

Drug: Abiraterone Acetate; Drug: Prednisone; Drug: Sunitinib

Group 2: AP + Dasatinib

EXPERIMENTAL

AP (Abiraterone Acetate + Prednisone) Plus Dasatinib; Randomized from AP group to receive Dasatinib if disease worsens. Assignment to crossover group AP + Sunitinib with further disease progression.

Drug: Abiraterone Acetate; Drug: Prednisone; Drug: Dasatinib

Interventions

Abiraterone Acetate DRUG

1000 mg by mouth each day of a 28 day cycle.

Also known as: CB7630

Abiraterone Acetate + Prednisone (AP); Group 1: AP + Sunitinib; Group 2: AP + Dasatinib

Prednisone DRUG

5 mg by mouth twice daily of a 28 day cycle.

Abiraterone Acetate + Prednisone (AP); Group 1: AP + Sunitinib; Group 2: AP + Dasatinib

Sunitinib DRUG

37.5 mg by mouth daily for two weeks followed by a week of rest in a 28 day cycle.

Also known as: Sunitinib Malate, SUO11248, Sutent

Group 1: AP + Sunitinib

Dasatinib DRUG

100 mg by mouth each day of a 28 day cycle.

Also known as: BMS-354825, Sprycel

Group 2: AP + Dasatinib

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent
• Male aged 18 years and above
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT or MRI.
• Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria
• Surgically or medically castrated, with testosterone levels of \</= 50 ng/dL (\</= 2.0 nM). If the patient is being treated with LHRH agonists (patients who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study.
• If the patient received previous anti-androgen therapy, then they have shown progression after withdrawal. Patients who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment (\>/= 4 weeks since last flutamide, \>/= 6 weeks since last bicalutamide or nilutamide). If progression is documented prior to this time interval, patients are eligible.
• Previous treatment with docetaxel is allowed. Patients must have recovered from any acute toxicity related to the treatment to be eligible.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of \</= 1.
• Hemoglobin \>/= 9.0 g/dL
• Platelet count \>/= 100,000/microL
• Serum albumin \>/= 3.5 g/dL
• Serum creatinine \</= 1.5 x ULN or a calculated creatinine clearance \>/= 60 mL/min
• Serum potassium \>/= 3.5 mmol/L
• Serum sodium, magnesium, potassium, phosphate, and calcium \>/= LLN (lower limit of normal)

You may not qualify if:

• Active infection (requiring oral or IV antibiotics) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone twice daily.
• Pathological finding consistent with small cell carcinoma of the prostate
• Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day 1. Patients who have received palliative radiation to a single site and recovered are eligible.
• No malignancy \[other than the one treated in this study\] which required radiotherapy or systemic treatment within the past 5 years.)
• Previously treated with ketoconazole (for prostate cancer) for greater than 7 consecutive days OR previously treated with any other -azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
• Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1)
• Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1)
• Uncontrolled hypertension (systolic BP \>/= 140 mmHg or diastolic BP \>/= 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
• Prolonged QTc interval on pre-entry electrocardiogram (\>/= 450 msec)
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• Known brain metastasis
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 50% at baseline
• History of significant bleeding disorder unrelated to cancer, including: i) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) ii) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) iii) Ongoing or recent (\</= 3 months) significant gastrointestinal bleeding

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• Janssen Scientific Affairs, LLC: collaborator
• Pfizer: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Sakellakis MJ, Hahn AW, Ramachandran S, Zhang M, Hoang A, Song JH, Liu J, Wang F, Basu HS, Sheperd P, Wang X, Frigo DE, Lin SH, Panaretakis T, Zhang J, Navone N, Troncoso P, Logothetis CJ, Titus MA. Characterization of prostate cancer adrenal metastases: dependence upon androgen receptor signaling and steroid hormones. Prostate Cancer Prostatic Dis. 2023 Dec;26(4):751-758. doi: 10.1038/s41391-022-00590-x. Epub 2022 Sep 13.

  PMID: 36100698 DERIVED

• Boukovala M, Spetsieris N, Weldon JA, Tsikkinis A, Hoang A, Aparicio A, Tu SM, Araujo JC, Zurita AJ, Corn PG, Pagliaro L, Kim J, Wang J, Subudhi SK, Tannir NM, Logothetis CJ, Troncoso P, Wen S, Efstathiou E. A candidate androgen signalling signature predictive of response to abiraterone acetate in men with metastatic castration-resistant prostate cancer. Eur J Cancer. 2020 Mar;127:67-75. doi: 10.1016/j.ejca.2019.12.027. Epub 2020 Jan 24.

  PMID: 31986451 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; Sunitinib; Dasatinib

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; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Sulfur Compounds; Organic Chemicals; Pyrimidines

Results Point of Contact

• Title: Paul Corn, MD
• Organization: The University of Texas MD Anderson Cancer Center

pcorn@mdanderson.org

(713) 563-7208

Study Officials

• Paul Corn, 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: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2010
• First Posted: December 7, 2010
• Study Start: March 16, 2011
• Primary Completion: December 7, 2023
• Study Completion: December 7, 2023
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2025-01

Locations

US (1)