- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02047253
Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment
A Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Chemotherapy and Androgen Pathway Inhibitors
Study Overview
Status
Intervention / Treatment
Detailed Description
First-line chemotherapy for metastatic castration-resistant prostate cancer (CRPC) combined with androgen inhibitors modestly extends overall survival. Carfilzomib is anticipated to enhance progression-free survival (PFS) as well as reduce pain and toxicities.
Proteasome inhibitors are promising agents used in the therapy of prostate cancer. Carfilzomib is a more potent and irreversible proteasome inhibitor than the frequently used proteasome inhibitor, Bortezomib. In Phase I trials Carfilzomib demonstrated substantial antitumor activity while exhibiting tolerable side effects.
Carfilzomib has been approved by the FDA for patients with multiple myeloma. The drug, however, is not approved for the use with CRPC patients. This trial will evaluate the tolerance and effectiveness of Carfilzomib in men with metastatic progressive CRPC following chemotherapy and androgen inhibitors.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
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Birmingham, Alabama, United States, 35233
- Birmingham VA Medical Center
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Georgia
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Macon, Georgia, United States, 31210
- Cancer Life Center, Navicent Health
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Louisiana
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New Orleans, Louisiana, United States, 70118
- University of Tulane
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically proven adenocarcinoma of the prostate
- Metastatic disease
- Progressive disease (PSA, radiologic, symptomatic) following abiraterone acetate and/or Enzalutamide (prior sipuleucel-T and chemotherapy are allowed); PSA progression is defined as baseline increase followed by any PSA increase ≥1 week apart.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Patients, even if surgically sterilized (i.e., status post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse if female partner of childbearing age.
- An elevated PSA level of >2ng/mL for patients progressing by PSA criteria is required (last confirmatory sample must be >2ng/mL)
- Currently on androgen ablation hormone therapy (a luteinizing hormone- releasing hormone (LHRH) agonist/antagonist or orchiectomy) with testosterone level <50ng/dL)
- Has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 - 2
- Left ventricular ejection fraction (LVEF) ≥40% on 2-D transthoracic echocardiogram (ECHO); Multi-gated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
- ≥19 years of age
- Resolution of all acute toxic effects of prior chemotherapy or surgical procedures to NCI CTCAE Version 4.03 Grade <1, in the opinion of the treating physician.
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patient has a platelet count of <100,000/mm3, or absolute neutrophil count of <1500/mm3 or Hemoglobin <8.0gm/dL
- Patient has a calculated or measured creatinine clearance of <30 milliliters (mL)/minute
- Patient has total bilirubin >2 x upper limit of normal (ULN), or aspartate aminotransferase (AST), alanine aminotransferase (ALT) >3.5 x ULN
- Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Before study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
- Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of: a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the breast; c) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.
- Known HIV, hepatitis B and hepatitis C infection
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization
- Prior treatment with bortezomib
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize Carfilzomib)
- Has received prior radiation to >50% of the bone marrow
- Has had significant bleeding/thrombosis in previous 4 weeks
- Has received treatment with radiation therapy, surgery, chemotherapy, or an investigational agent within 4 weeks prior to registration, (6 weeks for radiation therapy, radionuclides, nitrosoureas, or Mitomycin C) or who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Has evidence of uncontrolled Central Nervous System (CNS) involvement (previous radiation and off steroids is acceptable)
- Patients may not be receiving any other investigational agents
- Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection
- Is unable to comply with study requirements
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Carfilzomib
Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication.
The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur.
Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point.
Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient.
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Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle.
Other Names:
Administered prior to administration of Study drug
Administered orally twice daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: Baseline through 6 months for evaluating all patients
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The study will measure patient survival at 6 months but will continue to monitor overall survival as a secondary objective.
The Kaplan-Meier method will be used.
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Baseline through 6 months for evaluating all patients
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Overall Survival
Time Frame: From baseline through 36 months.
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Outcome measure was completed by using a count of participants.
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From baseline through 36 months.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Prostate-Specific Antigen (PSA) Changes
Time Frame: Baseline through 36 months
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PSA levels were collected at each visit on the day of treatment.
Linear regression with PSA as the dependent variable and time as the dependent variable was performed.
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Baseline through 36 months
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Number of Participants With Circulating Tumor Cell (CTC) Decline Over Three Time Points (Before Study Initiation, Day 1 of Cycles 2 and 4
Time Frame: Baseline through 36 months
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The CTC marker will be used to evaluate efficacy of response to treatment. CTC changes will include changes from unfavorable (less than or equal to 5/7.5 ml) to favorable and declines by >30%. Three collections: before study initiation, Day 1 of Cycles 2 and 4 |
Baseline through 36 months
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Assessment of Toxicities
Time Frame: Baseline through 36 months
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Hematologic and non-hematologic toxicities will be graded. The new international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) will serve as the guideline. On Day 1 of each cycle (4 weeks) for the duration of treatment and then 30 days following the last treatment |
Baseline through 36 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Guru Sonpavde, MD, University of Alabama at Birmingham
- Study Chair: Mansoor Saleh, MD, Georgia Cancer Specialists
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dexamethasone
- Acyclovir
Other Study ID Numbers
- F130725012 (UAB 1336)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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