Maximum Androgen Depletion

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Bristol-Myers Squibb
Ortho Biotech, Inc.
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01254864
First received: December 3, 2010
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to learn if adding either sunitinib malate or dasatinib to the combination of abiraterone acetate and prednisone can help to control prostate cancer. The safety of these drug combinations will also be studied.


Condition Intervention Phase
Prostate Cancer
Drug: Abiraterone Acetate
Drug: Prednisone
Drug: Sunitinib
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Maximal Androgen Depletion Followed by Randomization of Maximal Androgen Ablation With Molecular Targeted Therapies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall Final Failure Time [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Overall final failure time, defined as time to final failure in up to 3 courses from the start of therapy.


Estimated Enrollment: 180
Study Start Date: March 2011
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abiraterone Acetate + Prednisone (AP) Drug: Abiraterone Acetate
1000 mg by mouth each day of a 28 day cycle.
Other Name: CB7630
Drug: Prednisone
5 mg by mouth twice daily of a 28 day cycle.
Experimental: Group 1: AP + Sunitinib
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
1000 mg by mouth each day of a 28 day cycle.
Other Name: CB7630
Drug: Prednisone
5 mg by mouth twice daily of a 28 day cycle.
Drug: Sunitinib
37.5 mg by mouth daily for two weeks followed by a week of rest in a 28 day cycle.
Other Names:
  • Sunitinib Malate
  • SUO11248
  • Sutent
Experimental: Group 2: AP + Dasatinib
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
1000 mg by mouth each day of a 28 day cycle.
Other Name: CB7630
Drug: Prednisone
5 mg by mouth twice daily of a 28 day cycle.
Drug: Dasatinib
100 mg by mouth each day of a 28 day cycle.
Other Names:
  • BMS-354825
  • Sprycel

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide written informed consent
  2. Male aged 18 years and above
  3. Histologically or cytologically confirmed adenocarcinoma of the prostate
  4. Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT or MRI.
  5. Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria
  6. 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.
  7. 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.
  8. Previous treatment with docetaxel is allowed. Patients must have recovered from any acute toxicity related to the treatment to be eligible.
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status of </= 1.
  10. Hemoglobin >/= 9.0 g/dL
  11. Platelet count >/= 100,000/microL
  12. Serum albumin >/= 3.5 g/dL
  13. Serum creatinine </= 1.5 x ULN or a calculated creatinine clearance >/= 60 mL/min
  14. Serum potassium >/= 3.5 mmol/L
  15. Serum sodium, magnesium, potassium, phosphate, and calcium >/= LLN (lower limit of normal)
  16. ANC value >/= 1,000/mm^3
  17. Liver function: i. Serum bilirubin </= 1.5 x ULN (except for patients with documented Gilbert's disease) ii. AST or ALT </= 2.5 x ULN
  18. Able to swallow the study drug whole as a tablet/capsule.
  19. Patients who have partners of childbearing potential (.e.g. female that has not been surgically sterilized or who are not amenorrheic for >/= 12 months) must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator during the study and for 13 weeks after last study drug administration.
  20. Concomitant Medications (i) Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (at least 5 days prior). (ii) Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia; (iii) Patient agrees to discontinue use of drugs primarily metabolized by CYP3A4 enzyme; (iv) Patient agrees to discontinue use of H2 Inhibitors or proton inhibitors prior to dasatinib administration.

Exclusion Criteria:

  1. Active infection (requiring oral or IV antibiotics) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
  2. Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone twice daily.
  3. Pathological finding consistent with small cell carcinoma of the prostate
  4. 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.
  5. No malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years.)
  6. 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
  7. 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)
  8. 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)
  9. 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
  10. Prolonged QTc interval on pre-entry electrocardiogram (>/= 450 msec)
  11. Active or symptomatic viral hepatitis or chronic liver disease
  12. History of pituitary or adrenal dysfunction
  13. Known brain metastasis
  14. 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
  15. 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
  16. Atrial fibrillation or other cardiac arrhythmia requiring digitalis
  17. Other malignancy, except non-melanoma skin cancer, with a >/= 30% probability of recurrence within 24 months
  18. Clinically significant pleural effusion as determined by the Principal Investigator.
  19. Administration of an investigational therapy for prostate cancer within 30 days of Cycle 1, Day 1
  20. Any condition which, in the opinion of the investigator, would preclude participation in this trial.
  21. Patients taking category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib) i) quinidine, procainamide, disopyramide ii) amiodarone, sotalol, ibutilide, dofetilide iii) erythromycin, clarithromycin iv) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide v) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
  22. Prisoners or subjects who are involuntarily incarcerated.
  23. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01254864

Contacts
Contact: Christopher Logothetis, MD 713-792-2830

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Christopher Logothetis, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Ortho Biotech, Inc.
Pfizer
Investigators
Principal Investigator: Christopher Logothetis, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01254864     History of Changes
Other Study ID Numbers: 2010-0070, NCI-2011-00267
Study First Received: December 3, 2010
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Castrate resistant prostate cancer
Adenocarcinoma of the prostate
Sunitinib Malate
SUO11248
Sutent
BMS-354825
Sprycel

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Prednisone
Sunitinib
Dasatinib
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Glucocorticoids
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014