Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment

NCT02047253 | Completed Phase 2 Results DMC

• 1 other identifier: F130725012 (UAB 1336)
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

carfilzomib; prostate cancer; PSA (prostate-specific antigen); CRPC (castration-resistant prostate cancer)

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline through 6 months for evaluating all patients

• Overall Survival

  Outcome measure was completed by using a count of participants.

  From baseline through 36 months.

Secondary Outcomes (3)

• Number of Participants With Prostate-Specific Antigen (PSA) Changes

  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

  Baseline through 36 months

• Assessment of Toxicities

  Baseline through 36 months

Study Arms (1)

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.

Drug: Carfilzomib; Drug: Dexamethasone; Drug: Acyclovir

Interventions

Carfilzomib DRUG

Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle.

Also known as: Kyprolis

Carfilzomib

Dexamethasone DRUG

Administered prior to administration of Study drug

Carfilzomib

Acyclovir DRUG

Administered orally twice daily

Also known as: Zovirax

Carfilzomib

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Amgen: collaborator

Study Sites (4)

Birmingham VA Medical Center

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Cancer Life Center, Navicent Health

Macon, Georgia, 31210, United States

Location

University of Tulane

New Orleans, Louisiana, 70118, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Salivary Gland Adenoma, Pleomorphic

Interventions

carfilzomib; Dexamethasone; Acyclovir

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pam Dixon, RN, BSN, OCN
• Organization: University of Alabama at Birmingham

pamdixon@uab.edu

205-975-9875

Study Officials

• Guru Sonpavde, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Mansoor Saleh, MD

  Georgia Cancer Specialists

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 20, 2014
• First Posted: January 28, 2014
• Study Start: April 1, 2014
• Primary Completion: June 8, 2017
• Study Completion: July 14, 2017
• Last Updated: December 19, 2018
• Results First Posted: December 19, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)