UCDCC#215: Bicalutamide With or Without Everolimus in Treating Patients With Recurrent or Metastatic Prostate Cancer

• Sponsor: University of California, Davis (Other)
• Overall Status: Completed
• CT.gov ID: NCT00814788
• Collaborator: Novartis (Industry)
• Enrollment: 24
• Location: 1
• Arm: 1
• Duration (Months): 85
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying bicalutamide and everolimus to see how well they work compared with bicalutamide in treating patients with recurrent or metastatic prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Bicalutamide; Drug: Everolimus	Phase 2

Detailed Description

OBJECTIVES:

• To compare the PSA response rate in patients with hormone-independent recurrent or metastatic adenocarcinoma of the prostate treated with bicalutamide and everolimus after first-line androgen deprivation therapy.

• To evaluate the time to treatment failure and overall survival of these patients.

• To assess the toxicity of bicalutamide and everolimus in these patients.

OUTLINE: Patients are stratified according to disease status (metastatic disease vs biochemical recurrence without measurable disease).

Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 28-42 days and then every 3 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Bicalutamide and RAD001 in Patients With Hormone-Independent Prostatic Adenocarcinoma (HIPC) After the First-Line Androgen Deprivation Therapy
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bicalutamide + Everolimus Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Bicalutamide; 50 mg oral tablet daily; Other Names: Casodex ; Drug: Everolimus; 10 mg oral capsule daily; Other Names: Afinitor RAD001

Outcome Measures

Primary Outcome Measures

1. PSA Response Rate [Up to 2 years]

   The PSA response rate was defined as a 30% reduction in the PSA level from baseline. PSA Working Group consensus criteria combined with radiographic studies were used to determine the proportion of patients with PSA decline.

Secondary Outcome Measures

1. Progression-free Survival [Up to 2 years]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

2. Overall Survival [Up to 3 years]

   Overall survival was estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Participants must be adult males >18 years.

2. Patients must have histologically or cytologically confirmed CaP with a Gleason score available or interpretable.

3. Patients must have CaP deemed to be androgen independent.

4. Measurable disease is not required.

5. Patients must have been surgically or medically castrated. If the method of castration was LHRH agonists (leuprolide or goserelin) or antagonists (degarelix), then the patient must be willing to continue the use of LHRH agonists or antagonists. Serum testosterone must be at castrate levels (< 50 ng/dL) within 3 months prior to registration.

6. Participant has not been on any previous therapy with androgen receptor antagonists or mTOR inhibitors. Note: patients who have taken an androgen receptor antagonist for a brief period (no more than 2 months) at the start of LHRH agonist therapy to prevent flare will be considered eligible.

7. Men enrolled in this trial must agree to use adequate contraception prior to study entry and for the duration of study participation.

8. Patients must have normal organ and marrow function.

9. Ability to understand and the willingness to sign a written informed consent document

10. ECOG performance status 0-2.

11. Patients having any respiratory symptoms such as cough and shortness of breath have undergone pulmonary function testing revealing no worse than mild impairment.

Exclusion Criteria

1. No documented histological confirmation of CaP.

2. Patient has received other hormonal therapy besides first-line androgen deprivation therapy with LHRH agonist, LHRH antagonist, orchiectomy, high-dose steroid, abiraterone, provenge and ketoconazole.

3. Patients who have received prior treatment with an mTOR inhibitor.

4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

5. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with RAD001.

6. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)

7. Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.

8. Prior treatment with any investigational drug within the preceding 4 weeks.

9. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent.

10. Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.

11. Patients on herbs or other alternative medicines for the treatment of prostate cancer, including but not limited to saw palmetto, PC-SPES.

12. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.

13. Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin or other Stage 0 or I cancers.

14. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001.

15. Patients with an active, bleeding diathesis.

16. History of noncompliance to medical regimens.

17. Patients unwilling to or unable to comply with the protocol.

18. Patients with active pulmonary disorders or history of moderately to severely impaired pulmonary function tests will be excluded from the study.

19. Patients with symptomatic metastatic prostate cancer such as moderate to severe pain, impaired organ function or spinal cord compression will be excluded from this study unless these issues have been taken care of.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis Cancer Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis
• Novartis

Investigators

• Principal Investigator: Chong-Xian Pan, MD, PhD, University of California, Davis

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chow H, Ghosh PM, deVere White R, Evans CP, Dall'Era MA, Yap SA, Li Y, Beckett LA, Lara PN Jr, Pan CX. A phase 2 clinical trial of everolimus plus bicalutamide for castration-resistant prostate cancer. Cancer. 2016 Jun 15;122(12):1897-904. doi: 10.1002/cncr.29927. Epub 2016 Mar 28.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00814788
• Other Study ID Numbers: UCDCC#215; 223646; Novartis
• First Posted: Dec 25, 2008
• Last Update Posted: Jan 10, 2018
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of California, Davis: stage IV prostate cancer; adenocarcinoma of the prostate; recurrent prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Everolimus; Bicalutamide

Study Results

Participant Flow

Arm/Group Title	Bicalutamide + Everolimus
Arm/Group Description	Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bicalutamide 50 mg oral daily Everolimus: RAD001 10 mg oral capsule daily - continuously.
Period Title: Overall Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bicalutamide + Everolimus
Arm/Group Description	Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. bicalutamide: Bicalutamide 50 mg oral daily Everolimus: RAD001 10 mg oral capsule daily - continuously.
Overall Participants	24
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	71.1
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	24 100%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	PSA Response Rate
Description	The PSA response rate was defined as a 30% reduction in the PSA level from baseline. PSA Working Group consensus criteria combined with radiographic studies were used to determine the proportion of patients with PSA decline.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bicalutamide + Everolimus
Arm/Group Description	Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. bicalutamide: Bicalutamide 50 mg oral daily Everolimus: RAD001 10 mg oral capsule daily - continuously.
Measure Participants	24
Count of Participants [Participants]	18 75%

2. Secondary Outcome

Title	Progression-free Survival
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bicalutamide + Everolimus
Arm/Group Description	Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bicalutamide 50 mg oral daily Everolimus: RAD001 10 mg oral capsule daily - continuously.
Measure Participants	24
Median (95% Confidence Interval) [months]	9.4

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival was estimated using the Kaplan-Meier method.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bicalutamide + Everolimus
Arm/Group Description	Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bicalutamide: 50 mg oral tablet daily Everolimus: 10 mg oral capsule daily
Measure Participants	24
Median (95% Confidence Interval) [months]	28

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Bicalutamide + Everolimus
Arm/Group Description	Patients receive oral bicalutamide and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bicalutamide 50 mg oral daily Everolimus: RAD001 10 mg oral capsule daily - continuously.
All Cause Mortality
	Bicalutamide + Everolimus
	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)
Serious Adverse Events
	Bicalutamide + Everolimus
	Affected / at Risk (%)	# Events
Total	1/24 (4.2%)
General disorders
Sepsis	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Bicalutamide + Everolimus
	Affected / at Risk (%)	# Events
Total	17/24 (70.8%)
Blood and lymphatic system disorders
Anemia	14/24 (58.3%)	14
Edema	6/24 (25%)	6
Leukopenia	17/24 (70.8%)	17
Lymphopenia	16/24 (66.7%)	16
Neutropenia	9/24 (37.5%)	9
Proteinuria	3/24 (12.5%)	3
Thrombocytopenia	8/24 (33.3%)	8
Cardiac disorders
Hypercholesterolemia	15/24 (62.5%)	15
Hypertriglyceridemia	13/24 (54.2%)	13
Gastrointestinal disorders
Abdominal pain	3/24 (12.5%)	3
Constipation	3/24 (12.5%)	3
Diarrhea	4/24 (16.7%)	4
Nausea	1/24 (4.2%)	1
General disorders
Anal mucositis	1/24 (4.2%)	1
Constitutional Symptoms	1/24 (4.2%)	1
Dry mouth	1/24 (4.2%)	1
Fatigue	16/24 (66.7%)	16
Taste Alteration	4/24 (16.7%)	4
Weight Loss	2/24 (8.3%)	2
Hepatobiliary disorders
ALT increase	4/24 (16.7%)	4
ALK phosphastase increased	6/24 (25%)	6
AST increased	8/24 (33.3%)	8
Musculoskeletal and connective tissue disorders
Right hip pain	1/24 (4.2%)	1
Psychiatric disorders
Anorexia	5/24 (20.8%)	5
Renal and urinary disorders
Hyperglycemia	12/24 (50%)	12
Renal Failure	2/24 (8.3%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/24 (12.5%)	3
Pneumonitis	6/24 (25%)	6
Pneumonia	1/24 (4.2%)	1
Skin and subcutaneous tissue disorders
Acne	1/24 (4.2%)	1
Dry skin	2/24 (8.3%)	2
Hand Foot Syndrome	1/24 (4.2%)	1
Oral mucositis	14/24 (58.3%)	14
Pruritus	2/24 (8.3%)	2
Rash	5/24 (20.8%)	5
Vascular disorders
Deep Vein Thrombosis	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.