Metastatic Castration-resistant Prostate CancerPhase 2NCT02047253
Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment
A Phase 2 study testing Carfilzomib, Dexamethasone and Acyclovir in people with Metastatic Castration-resistant Prostate Cancer, run by University of Alabama at Birmingham at 4 sites in United States.
Trial summary
This study will test how effective the drug, Carfilzomib, reduces progression of prostate cancer in patients who have previously received chemotherapy and androgen inhibitors. Carfilzomib is approved for multiple myeloma but is not approved for prostate cancer. Therefore, it is considered investigational. Read more about this study
- Who is it for?
- Ages 19 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- Carfilzomib, Dexamethasone and Acyclovir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2014to 14 Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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)
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Birmingham VA Medical Center
Birmingham, Alabama, 35233
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Cancer Life Center, Navicent Health
Macon, Georgia, 31210
University of Tulane
New Orleans, Louisiana, 70118
About this study
Official title: A Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Chemotherapy and Androgen Pathway Inhibitors
This study will test how effective the drug, Carfilzomib, reduces progression of prostate cancer in patients who have previously received chemotherapy and androgen inhibitors. Carfilzomib is approved for multiple myeloma but is not approved for prostate cancer. Therefore, it is considered investigational. Other approved methods of treatment for metastatic prostate cancer have demonstrated only modest benefits. Novel and tolerable agents are necessary to make further gains and extend overall survival.
Read the 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.
- Being tested
- Carfilzomib, Dexamethasone, Acyclovir
- Keywords
- carfilzomib, prostate cancer, PSA (prostate-specific antigen), CRPC (castration-resistant prostate cancer)
- Medical subject headings
- Prostatic Neoplasms, Salivary Gland Adenoma, Pleomorphic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis
Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle.
DexamethasoneDrug
Administered prior to administration of Study drug
AcyclovirDrug
Also called Zovirax
Administered orally twice daily
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib | Experimental | 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. Receives: Drug: Carfilzomib; Drug: Dexamethasone; Drug: Acyclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
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.
Measured: Baseline through 6 months for evaluating all patients
Overall Survival
Outcome measure was completed by using a count of participants.
Measured: From baseline through 36 months.
Secondary outcomes (3)
Number of Participants With Prostate-Specific Antigen (PSA) Changes
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.
Measured: Baseline through 36 months
Number of Participants With Circulating Tumor Cell (CTC) Decline Over Three Time Points (Before Study Initiation, Day 1 of Cycles 2 and 4
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
Measured: Baseline through 36 months
Assessment of Toxicities
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
Measured: Baseline through 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2014 (estimated)
- Study startApr 2014
- Primary completion8 Jun 2017
- Study completion14 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Guru Sonpavde, MD, University of Alabama at Birmingham
- Investigators
- Guru Sonpavde, MD, Principal investigator, University of Alabama at BirminghamMansoor Saleh, MD, Study chair, Georgia Cancer Specialists
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02047253
- Sponsor's protocol ID
- F130725012 (UAB 1336)
- Status last verified
- Nov 2018
- First submitted
- 20 Jan 2014
- Last updated
- 19 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Chemotherapy and Androgen Pathway Inhibitors
- ClinicalTrials.gov ID
- NCT02047253
- Acronym / sponsor ID
- F130725012 (UAB 1336)
- Keywords
- carfilzomib, prostate cancer, PSA (prostate-specific antigen), CRPC (castration-resistant prostate cancer)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Apr 2014 (actual)
- Primary completion
- 8 Jun 2017 (actual)
- Study completion
- 14 Jul 2017 (actual)
- First posted
- 28 Jan 2014 (estimated)
- Results
- Posted 19 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test how effective the drug, Carfilzomib, reduces progression of prostate cancer in patients who have previously received chemotherapy and androgen inhibitors. Carfilzomib is approved for multiple myeloma but is not approved for prostate cancer. Therefore, it is considered investigational. Other approved methods of treatment for metastatic prostate cancer have demonstrated only modest benefits. Novel and tolerable agents are necessary to make further gains and extend overall survival.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib | Experimental | Drug: Carfilzomib, Drug: Dexamethasone, Drug: AcyclovirCarfilzomib 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: KyprolisCarfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle. | Drug | Carfilzomib |
| DexamethasoneAdministered prior to administration of Study drug | Drug | Carfilzomib |
| AcyclovirAlso: ZoviraxAdministered orally twice daily | Drug | Carfilzomib |
Primary outcome
Progression-free Survival (PFS)
Time frame: Baseline through 6 months for evaluating all patients
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.
Overall Survival
Time frame: From baseline through 36 months.
Outcome measure was completed by using a count of participants.
3 secondary outcomes
Number of Participants With Prostate-Specific Antigen (PSA) Changes
Time frame: Baseline through 36 months
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
Assessment of Toxicities
Time frame: Baseline through 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Metastatic Castration-resistant Prostate Cancer
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NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
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ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
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Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guru Sonpavde, MD principal investigator
University of Alabama at Birmingham
Mansoor Saleh, MD study chair
Georgia Cancer Specialists
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carfilzomib, Dexamethasone and Acyclovir in people with Metastatic Castration-resistant Prostate Cancer, run by University of Alabama at Birmingham at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: Baseline through 6 months for evaluating all patients). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2018.