BKM120+Abiraterone Acetate for Metastatic CRPC

Phase Ib Study of BKM120 Combined With Abiraterone Acetate for Docetaxel-pretreated, Castrate-resistant, Metastatic Prostate Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: BKM120; Drug: Abiraterone; Drug: Prednisone

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Beth-Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Profile and MTD for BKM120/Abiraterone/Prednisone	Determine the safety profile and MTD for the combination of BKM120 and abiraterone plus prednisone	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response in Expansion Cohort	Determine duration time of response (time to progression) in the expansion cohort	2 years
Impact of PTEN Status on Response Rate/Duration	Assess the impact of PTEN status on response rate and duration of response	2 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute

Publications and helpful links

Helpful Links

• Beth Israel Deaconess Medical Center Cancer Clinical Trials Office.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): December 29, 2014
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: December 3, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: February 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Metastatic; Castrate Resistant; Docetaxel Pretreated
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 12-121