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

VELCADE® (Bortezomib) for Injection Therapy for Early Relapsed Prostate Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Velcade; Drug: LH-RH Agonist; Drug: Androgen Receptor Antagonists

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates, PA
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate-specific Antigen (PSA) Response		3 months after the start of treatment
Time to PSA Progression	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.	From on study until time of PSA progression for up to two years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Andrew S. Kraft, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: February 7, 2005
• First Submitted That Met QC Criteria: February 7, 2005
• First Posted (Estimate): February 8, 2005

Study Record Updates

• Last Update Posted (Actual): November 5, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Bortezomib; Androgens; Androgen Receptor Antagonists
• Other Study ID Numbers: CDR0000406013; MUSC-031218; MUSC-HR-11357