Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)

NCT00452387 | Terminated Phase 2 Results

• 1 other identifier: ACORN AVAHRPC0607
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this research study is to determine if the combination of mitoxantrone, prednisone and sorafenib will improve the time to progression of advanced stage metastatic hormone-refractory prostate cancer.

Conditions

Metastatic Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Median Time to Progression (TTP) by Imaging

  Time to progression is defined as the time from treatment start until objective tumor progression. The median time to progression is the parameter used to describe TTP.

  Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.

Secondary Outcomes (3)

• Correlation of Biochemical Criteria (PSA, Prostate-specific Antigen) With Objective Imaging

  PSA was evaluated on day 1 of every cycle (approximately every 3 weeks) during study treatment. Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.

• Quality of Life (QoL)

  The Patient Care Monitor questionnaire was administered on day 1 of every cycle (approximately every 3 weeks) during study treatment.

• Median Overall Survival (OS)

  Overall survival was measured from day 1 of treatment until the end of treatment and then every 3 months thereafter until death.

Interventions

Mitoxantrone DRUG

Once six patients are accrued at dose level 1, the maximum tolerated dose (MTD) will be assessed by following them through one cycle of treatment. If 2/6 patients experience dose limiting toxicity (DLT) at the 400 mg twice a day (bid) level then the MTD will be defined as 400 mg daily (QD). Additional patients will be enrolled at the MTD for the phase II portion. Dose Level -2, Mitoxantrone 9mg/m2 Dose Level -1 Mitoxantrone 12mg/m2 Dose Level 1 Mitoxantrone 12mg/m2

Also known as: Novantrone

Prednisone DRUG

Once six patients are accrued at dose level 1, the maximum tolerated dose (MTD) will be assessed by following them through one cycle of treatment. If 2/6 patients experience dose limiting toxicity (DLT) at the 400 mg twice a day (bid) level then the MTD will be defined as 400 mg daily (QD). Additional patients will be enrolled at the MTD for the phase II portion. Dose Level -2, Prednisone 5mg bid Dose Level -1 Prednisone 5mg bid Dose Level 1 Prednisone 5mg bid

Also known as: Deltasone

Sorafenib DRUG

Once six patients are accrued at dose level 1, the maximum tolerated dose (MTD) will be assessed by following them through one cycle of treatment. If 2/6 patients experience dose limiting toxicity (DLT) at the 400 mg twice a day (bid) level then the MTD will be defined as 400 mg daily (QD). Additional patients will be enrolled at the MTD for the phase II portion. Dose Level -2, Sorafenib 400 mg QD Dose Level -1 Sorafenib 400 mg QD Dose Level 1 Sorafenib 400 mg bid

Also known as: Nexavar

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent
• Histopathologic diagnosis of prostatic adenocarcinoma with evidence of progression despite adequate castration (testosterone \< 50 ng/dL)
• Progressive disease after taxane-based chemotherapy (docetaxel or paclitaxel, single agent or combination regimens, weekly or every 21 day schedules)
• Patients who discontinued taxane- based chemotherapy because of toxicity will be eligible as long as there is evidence of progressive disease
• Minimum of 4 weeks period from last chemotherapy infusion to registration (this does not apply to steroid use which is permitted). Estramustine needs to be discontinued at least 6 weeks prior to first day of treatment on protocol
• A minimum of 4 weeks off bicalutamide, nilutamide, megestrol acetate ketoconazole, diethylstilbestrol (DES). Minimum of 2 weeks off flutamide
• Reductase inhibitors will be allowed if initiated at least 2 months prior to registration
• No concurrent investigational therapy
• Complementary and Alternative Medicine (CAM) products will be permitted as long as patients have been receiving them for at least 2 months. Initiation of new CAM products while on protocol will be discouraged.
• Ongoing androgen deprivation therapy (orchiectomy, gonadotropin-releasing hormone (GnRH) agonist or antagonist)
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin ≥ 9.0 g/dl
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

You may not qualify if:

• More than one line of prior cytotoxic chemotherapy in the metastatic setting, previous adjuvant chemotherapy will be allowed
• No active malignancy other than prostate cancer (except non-melanoma skin cancer) within 5 years of enrollment
• Known brain metastases
• Cardiac disease: Congestive heart failure \> class II New York Heart Association (NYHA). Patients must not have unstable angina or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Uncontrolled hypertension
• Active clinically serious infection \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
• Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug
• Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug
• Poorly controlled hyperglycemia
• Treatment with radiotherapy within 4 weeks or treatment with radiopharmaceuticals within past 8 weeks
• Patient has received other investigational drugs within 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Serious non-healing wound or ulcer

Sponsors & Collaborators

• Accelerated Community Oncology Research Network: lead
• Bayer: collaborator

Study Sites (10)

Wilshire Oncology Medical Group, Inc.

La Verne, California, 91750, United States

Location

Peachtree Hematology Oncology Consultants

Atlanta, Georgia, 30309, United States

Location

Central Georgia Cancer Care

Macon, Georgia, 31201, United States

Location

Northwest Georgia Oncology Centers

Marietta, Georgia, 30060, United States

Location

Hematology Oncology Centers of the Northern Rockies, PC

Billings, Montana, 59101, United States

Location

Mid-Ohio Oncology/Hematology, Inc.

Columbus, Ohio, 43213, United States

Location

Lancaster Cancer Center

Lancaster, Pennsylvania, 17605, United States

Location

Pennsylvania Oncology Hematmology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Cancer Specialists of Tidewater

Chesapeake, Virginia, 23320, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Mitoxantrone; Prednisone; Sorafenib

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)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Early termination, according to the stopping rule included in the protocol, leading to a small number of subjects analyzed

Results Point of Contact

• Title: Vice President of Scientific Affairs
• Organization: Accelerated Community Oncology Research Network, Inc.

mwalker@acorncro.com

Study Officials

• Vasily Assikis, MD

  Peachtree Hematology Oncology Consultants

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2007
• First Posted: March 27, 2007
• Study Start: May 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: January 1, 2009
• Last Updated: September 16, 2011
• Results First Posted: May 26, 2010

Record last verified: 2011-09

Locations

US (10)