Bortezomib With or Without Hormone Therapy in Treating Patients With Relapsed Prostate Cancer

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00103376
• Collaborator: (none)
• Enrollment: 23
• Locations: 4
• Arms: 2
• Duration (Months): 80
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Androgens can cause the growth of prostate cancer cells. Drugs, such as goserelin, leuprolide, flutamide, or bicalutamide, may stop the adrenal glands from making androgens. Giving bortezomib with hormone therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bortezomib with or without hormone therapy works in treating patients with relapsed prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Velcade; Drug: LH-RH Agonist; Drug: Androgen Receptor Antagonists	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: VELCADE® (Bortezomib) for Injection Therapy for Early Relapsed Prostate Cancer
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Velcade Patient will complete Part A (Velcade only). If the patient has a complete response, he will come off study. If the patient has progressive disease, he will start Part B (Velcade + antiandrogen). If the patient has a partial response or stable disease, he will start Part B after at least a 7-day break.	Drug: Velcade; Part A: 1.3 mg/m2 administered on days 1, 4, 8 and 11 followed by 10 days rest. A second cycle will be given at the same schedule. Cycle 3 will include 3 weekly injections. Part B: 1.3mg/m2 administered weekly for 3 weeks followed by 1 week break; Other Names: bortezomib
Experimental: Part B: Velcade+LH-RH antagonist+Androgen receptor antagonist Patient will start Part B after completing Part A or may be enrolled to part B only.	Drug: Velcade; Part A: 1.3 mg/m2 administered on days 1, 4, 8 and 11 followed by 10 days rest. A second cycle will be given at the same schedule. Cycle 3 will include 3 weekly injections. Part B: 1.3mg/m2 administered weekly for 3 weeks followed by 1 week break; Other Names: bortezomib ; Drug: LH-RH Agonist; given as a 3 month depo-injection; Drug: Androgen Receptor Antagonists; given orally daily for 3 months

Outcome Measures

Primary Outcome Measures

1. Prostate-specific Antigen (PSA) Response [3 months after the start of treatment]

2. Time to PSA Progression [From on study until time of PSA progression for up to two years]

   PSA progression is defined as a PSA increase of 50% over the nadir CR or CR/PR value on three successive PSA measurements two months apart to a value of >= 1.0 ng/ml.

Secondary Outcome Measures

1. Number of Patients Who Experienced an Adverse Event by CTCAE v. 2.0 [From start of treatment until end of study, up to 6 months]

2. Disease-free Interval [3 months after combined treatment]

   This will only be analyzed if sample size warrants the analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Relapsed disease after definitive local therapy, as documented only by a rise in prostate-specific antigen (PSA)

• Experienced PSA relapse after definitive local therapy

• Rising PSA (≥ 1.0 ng/mL after nadir < 1.0 ng/mL)

• PSA increase of ≥ 0.3 ng/mL (increase occurred between 2 separate measurements taken ≥ 4 weeks apart)

• The first of these two PSA values must rise above a previously recorded post-therapy nadir value

• Ineligible for curative therapy

• No clinical evidence of local recurrence (i.e., palpable induration or mass in the prostatic fossa) other than PSA elevation

• No evidence of palpable disease in the prostatic bed

• No metastatic disease (M0)

• No non-nodal (> N1) metastasis

• No evidence of osseous metastasis on bone scan within the past 28 days

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-1

Life expectancy

• At least 1 year

Hematopoietic

• Platelet count ≥ 30,000/mm^3

• Absolute neutrophil count ≥ 1,000/mm^3

Hepatic

• No known hepatitis B or C positivity

Renal

• Creatinine clearance ≥ 30 mL/min

Immunologic

• No known human T-cell lymphotropic virus positivity

• No hypersensitivity to bortezomib, boron, or mannitol

• No known HIV 1 or 2 positivity

• No active, ongoing bacterial, viral, or fungal infection

Other

• Fertile patients must use effective contraception

• No peripheral neuropathy ≥ grade 2

• No other disease, condition, or social or geographic constraint that would preclude study participation

• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

• At least 6 months since prior hormonal therapy combined with radiation therapy as definitive therapy

• Neoadjuvant hormonal therapy prior to definitive therapy (e.g., surgery, radiation therapy, brachytherapy, or cryoablation) allowed

• No other concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics

• More than 12 months since prior radioactive seed therapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

• More than 4 weeks since prior surgery

• No concurrent surgery

Other

• No concurrent second-line herbal preparations, including PC-SPES

• No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
2	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
3	South Carolina Oncology Associates, PA	Columbia	South Carolina	United States	29210
4	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303

Sponsors and Collaborators

• Medical University of South Carolina

Investigators

• Principal Investigator: Andrew S. Kraft, MD, Medical University of South Carolina
• Study Chair: Gustavo Leone, Medical University of South Carolina, Hollings Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00103376
• Other Study ID Numbers: CDR0000406013; MUSC-031218; MUSC-HR-11357
• First Posted: Feb 8, 2005
• Last Update Posted: Nov 5, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Medical University of South Carolina: adenocarcinoma of the prostate; recurrent prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Bortezomib; Androgens; Androgen Receptor Antagonists

Study Results

Participant Flow

Arm/Group Title	Part A Only: Velcade	Part B (Velcade+LH-RH Antagonist+Adrogen Receptor)	Part A + Part B
Arm/Group Description	Patients who were enrolled to Part A but did not move on to Part B	Patients who were enrolled only to part B.	Patients who completed part A and moved in to Part B.
Period Title: Overall Study
STARTED	8	7	8
COMPLETED	8	7	8
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Part A Only: Velcade	Part B (Velcade + LH-RH Antagonist+Androgen Receptro	Part A + Part B	Total
Arm/Group Description	Patients who were enrolled to Part A but did not move on to Part B.	Patients who were enrolled only to part B	Patients who completed part A and moved in to part B.	Total of all reporting groups
Overall Participants	8	7	8	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 12.5%	3 42.9%	4 50%	8 34.8%
>=65 years	7 87.5%	4 57.1%	4 50%	15 65.2%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	8 100%	7 100%	8 100%	23 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 12.5%	1 14.3%	1 12.5%	3 13%
White	7 87.5%	6 85.7%	7 87.5%	20 87%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	7 100%	8 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Prostate-specific Antigen (PSA) Response
Time Frame	3 months after the start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A: Velcade	Part B: (Velcade+LH-RH Antagonist+Adrogen Receptor)	Part A + Part B
Arm/Group Description	Patients who were enrolled to Part A but did not move on to Part B	Patients who were enrolled only to part B.	Patients who completed part A and moved in to Part B.
Measure Participants	8	7	8
Number [participants]	1 12.5%	6 85.7%	5 62.5%

2. Primary Outcome

Title	Time to PSA Progression
Description	PSA progression is defined as a PSA increase of 50% over the nadir CR or CR/PR value on three successive PSA measurements two months apart to a value of >= 1.0 ng/ml.
Time Frame	From on study until time of PSA progression for up to two years

Outcome Measure Data

Analysis Population Description

Only patients with a CR were included in the analysis. No patients in Part A had a complete response. Time to progression for Part B only and Part A+Part B was calculated together. The information for the confidence interval is not available.

Arm/Group Title	Part A Only: Velcade	Part B and Part A + Part B
Arm/Group Description	Patients who were enrolled to Part A but did not move on to Part B.	Patients who were enrolled to Part B (Velcade + LH-RH Antagonist+Androgen Receptor) and Part A (Velcade only) + Part B
Measure Participants	0	11
Median (95% Confidence Interval) [months]	5.49

3. Secondary Outcome

Title	Number of Patients Who Experienced an Adverse Event by CTCAE v. 2.0
Time Frame	From start of treatment until end of study, up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part A Only: Velcade	Part B (Velcade+Lh-RH Antagonist+ Androgen Receptor)	Part A + Part B
Arm/Group Description	Patients who were enrolled to Part A but did not move on to Part B	patients who were enrolled only to Part B.	Patients who completed Part A and moved in to Part B
Measure Participants	8	7	8
Number [participants]	8 100%	7 100%	8 100%

4. Secondary Outcome

Title	Disease-free Interval
Description	This will only be analyzed if sample size warrants the analysis.
Time Frame	3 months after combined treatment

Outcome Measure Data

Analysis Population Description

data was not collected for this outcome measure.

Arm/Group Title	Velcade and Hormonal Therapy
Arm/Group Description	Patient will complete Part A (Velcade only). If the patient has a complete response, he will come off study. If the patient has progressive disease, he will start Velcade + Antiandrogen therapy. If the patient has a partial response or stable disease, he will start Velcade+antiandrogen after at least a 7-day break. After 3 months on Part B, if the patient has a complete response, he will come off study. Patients with a partial response or stable disease will repeat part B. Patients with progressive disease will come off study. Velcade: Part A: 1.3 mg/m2 administered on days 1, 4, 8 and 11 followed by 10 days rest. A second cycle will be given at the same schedule. Cycle 3 will include 3 weekly injections. Part B: 1.3mg/m2 administered weekly for 3 weeks followed by 1 week break LH-RH Agonist: given as a 3 month depo-injection Androgen Receptor Antagonists: given orally daily for 3 months
Measure Participants	0

Adverse Events

Time Frame	from start of treatment until end of study visit, about 6 months
Arm/Group Title	Part A: Velcade Only		Part B (Velcade+LH-RH Antagonist+Adrogen Receptor)		Part A + Part B
Arm/Group Description	Patients who were enrolled to Part A but did not move on to Part B		Patients who were enrolled only to part B.		Patients who completed part A and moved in to Part B.
All Cause Mortality
	Part A: Velcade Only		Part B (Velcade+LH-RH Antagonist+Adrogen Receptor)		Part A + Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Velcade Only		Part B (Velcade+LH-RH Antagonist+Adrogen Receptor)		Part A + Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/7 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
back pain	1/8 (12.5%)	1	0/7 (0%)	1	0/8 (0%)	1
Other (Not Including Serious) Adverse Events
	Part A: Velcade Only		Part B (Velcade+LH-RH Antagonist+Adrogen Receptor)		Part A + Part B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		7/7 (100%)		8/8 (100%)
Blood and lymphatic system disorders
anemia	5/8 (62.5%)		0/7 (0%)		7/8 (87.5%)
thrombocytopenia	7/8 (87.5%)		0/7 (0%)		8/8 (100%)
neutropenia	6/8 (75%)		0/7 (0%)		5/8 (62.5%)
Gastrointestinal disorders
constipation	6/8 (75%)		4/7 (57.1%)		8/8 (100%)
ileus	2/8 (25%)		0/7 (0%)		0/8 (0%)
vomiting	2/8 (25%)		3/7 (42.9%)		2/8 (25%)
General disorders
fatigue	8/8 (100%)		5/7 (71.4%)		6/8 (75%)
anorexia	2/8 (25%)		0/7 (0%)		4/8 (50%)
pain	8/8 (100%)		4/7 (57.1%)		8/8 (100%)
dizziness	3/8 (37.5%)		1/7 (14.3%)		1/8 (12.5%)
Infections and infestations
infection	1/8 (12.5%)		0/7 (0%)		1/8 (12.5%)
shingles	1/8 (12.5%)		0/7 (0%)		1/8 (12.5%)
Musculoskeletal and connective tissue disorders
weakness	2/8 (25%)		0/7 (0%)		1/8 (12.5%)
Nervous system disorders
neuropathy	8/8 (100%)		0/7 (0%)		8/8 (100%)
Psychiatric disorders
insomnia	3/8 (37.5%)		0/7 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
dyspnea	1/8 (12.5%)		0/7 (0%)		0/8 (0%)
Vascular disorders
hypotension	1/8 (12.5%)		1/7 (14.3%)		2/8 (25%)

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.