BKM120+Abiraterone Acetate for Metastatic CRPC

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Dana-Farber Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Glenn Bubley, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01741753
First received: December 3, 2012
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational drug, in this case an investigational drug combined with standard drug therapy. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is still being studied and taht research doctors are trying to find out more about it. It also means that the FDA has not approved the drug for use in patients, including people with your type of cancer.

BKM120 is a drug that inhibits the ability of tumors to grow and survive, which may lead to better outcomes in many types of cancer.

Abiraterone acetate is a drug that is approved for the treatment of prostate cancer, and works by inhibiting an enzyme found in prostate tumor tissue. While taking abiraterone acetate, individuals must also take a glucocorticoid such as prednisone.

Most patients with castrate-resistant prostate cancer will receive treatment with docetaxel, after which treatment with the combination of abiraterone and prednisone has been shown to be effective. Evidence has shown an interaction between the pathways through which BKM120 and abiraterone act on cancer. Therefore, it is thought that the treatment of castrate-resistant prostate cancer will be enhanced by combining BKM120 with abiraterone plus prednisone. The purpose of this study is to determine a safe dose for the combination of daily oral BKM120, abiraterone acetate, and prednisone in patients with castrate-resistant metastatic prostate cancer who have received prior treatment with docetaxel.


Condition Intervention Phase
Prostate Cancer
Drug: BKM120
Drug: Abiraterone
Drug: Prednisone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ib Study of BKM120 Combined With Abiraterone Acetate for Docetaxel-pretreated, Castrate-resistant, Metastatic Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Safety Profile and MTD for BKM120/Abiraterone/Prednisone [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Determine the safety profile and MTD for the combination of BKM120 and abiraterone plus prednisone


Secondary Outcome Measures:
  • Duration of Response in Expansion Cohort [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determine duration time of response (time to progression) in the expansion cohort

  • Impact of PTEN Status on Response Rate/Duration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess the impact of PTEN status on response rate and duration of response


Estimated Enrollment: 33
Study Start Date: November 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
BKM120+Abiraterone+Prednisone
Drug: BKM120
Orally, every morning
Drug: Abiraterone
Orally, 1000 mg, every morning
Drug: Prednisone
Orally, 5 mg, every morning

Detailed Description:

You will undergo a screening process to determine if you are eligible to participate in this trial. This process will include the following procedures: Tumor Biopsy, including a bone marrow biopsy, which is used to determine the kinds of cancer cells in your tumor and a Physical Examination, including weight, blood pressure, heart rate, respiratory rate and body temperature.

Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have docetaxel resistant CRPC, not everyone who participates in this research study will receive the same dose of the study drug. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses.

If you take part in this research study, you will be given a study drug-dosing calendar for each treatment cycle. There will be a 14 day lead in phase of BKM120 alone to assess for toxicity from this agent. After the lead in phase, the standard dose of abiraterone and prednisone will be added to the BKM120 treatment regimen. Treatment cycles will last 4 weeks (28 days), during which time you will be taking the study drug in combination with the standard drug therapy once daily. Your time of participation in the study will be based on how well you tolerate the experimental drug. You could be participating in the study for a period of days, or years, depending on the course of your cancer.

During each treatment cycle, you will be required to return to see your research doctor for a study visit on Day 1 of each cycle. For Cycle 1, you will also need to return on Days 8, 15 and 22.

The following procedures will be performed and samples will be collected at 1 or more study visits: Evaluation of side effects, Vital sign measurement, Heart function tests, Neuropsychologic exams, Performance status assessment, Tumor biopsy, Assessment of tumor, Blood samples.

We would like to keep track of your medical condition for the rest of your life. We would like to do this by calling you on the telephone once a year to see how you are doing. Keeping in touch with you and checking your condition every year will help us look at the long-term effects of the research study. You will be required to return to see your research doctor for an end of study visit, which will take place 4-8 weeks after you undergo prostatectomy.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed CRPC with metastatic bone disease
  • Castrate resistant disease
  • Life expectancy of at least 6 months
  • At least four weeks from previous treatment
  • At least four weeks since any major surgery or radiation therapy
  • Using highly effective contraception

Exclusion Criteria:

  • Thromboembolism within past 6 months
  • History of diabetes
  • Prior therapy with abiraterone
  • Prior therapy with PI3K inhibitor
  • Alcohol or drug dependence currently or within past 6 months
  • Contraindications to biopsy, such as bleeding disorders
  • On anticoagulants such as warfarin or heparin
  • Active malignancy other than skin cancer or superficial bladder cancer
  • Untreated brain metastases
  • Acute or chronic liver, renal disease or pancreatitis
  • Mood disorders judged by the investigator to interfere with study participation
  • Active cardiac disease or history of cardiac dysfunction
  • Uncontrolled hypertension
  • Known HIV, Hepatitis B or C
  • Serious non-healing wound, ulcer or bone fracture
  • Known or suspected allergy to BKM120, abiraterone or prednisone
  • Impairment of GI function
  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: NCT01741753

Contacts
Contact: Glenn Bubley, MD 6177352062 gbubley@bidmc.harvard.edu

Locations
United States, Massachusetts
Beth-Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Glenn Bubley, MD    617-735-2062    gbubley@bidmc.harvard.edu   
Principal Investigator: Glenn Bubley, MD         
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Mary Ellen Taplin, MD    617-632-3237    mtaplin@partners.org   
Principal Investigator: Mary Ellen Taplin, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Glenn Bubley, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01741753     History of Changes
Other Study ID Numbers: 12-121
Study First Received: December 3, 2012
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Docetaxel Pretreated
Castrate Resistant
Metastatic

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 22, 2014