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

Sponsor:	Accelerated Community Oncology Research Network
Collaborator:	Bayer
Information provided by (Responsible Party):	Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:	NCT00452387

Purpose

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.

Condition	Intervention	Phase
Metastatic Prostate Cancer	Drug: Mitoxantrone Drug: Prednisone Drug: Sorafenib	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Prednisone Mitoxantrone Mitoxantrone hydrochloride Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Accelerated Community Oncology Research Network:

Primary Outcome Measures:

Median Time to Progression (TTP) by Imaging [ Time Frame: Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment. ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Correlation of Biochemical Criteria (PSA, Prostate-specific Antigen) With Objective Imaging [ Time Frame: 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. ] [ Designated as safety issue: No ]
The test of association assesses the null hypothesis that the frequency of PSA response is the same for patients with and without a favorable imaging response. PSA response required a 50% reduction of the baseline PSA result that was confirmed three weeks later. Favorable imaging response is defined as stable disease, partial response, or complete response per RECIST guidelines. The Fisher's exact test was used to test this hypothesis.
Quality of Life (QoL) [ Time Frame: The Patient Care Monitor questionnaire was administered on day 1 of every cycle (approximately every 3 weeks) during study treatment. ] [ Designated as safety issue: No ]
The subject answers questions from the following 6 categories: general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation. Each question has a scale from 0 through 10, where 0 is not a problem and 10 is as bad as possible. The scores for the 6 categories are combined and normalized, and used to describe overall quality of life. Because normalized scores are created using a look-up index, there is no clearly defined maximum value. In practice, the maximum value for the combined scale is 73.5.
Median Overall Survival (OS) [ Time Frame: Overall survival was measured from day 1 of treatment until the end of treatment and then every 3 months thereafter until death. ] [ Designated as safety issue: No ]
Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS.

Enrollment:	22
Study Start Date:	May 2007
Study Completion Date:	January 2009
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Intervention Details:

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

Other Name: Novantrone

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

Other Name: Deltasone

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

Other Name: Nexavar

Detailed Description:

The primary objective of this study is to test the hypothesis that the combination of Mitoxantrone, Prednisone and Sorafenib in taxane-refractory patients with metastatic hormone refractory prostate cancer (mHRPC) will result in an improvement of the median time to progression (TTP). Since the median (i.e 50% of patients) TTP for Mitoxantrone/Prednisone is 3 months, our hypothesis is that 70% will have not progressed at 3 months with this investigational combination. Progression will be assessed by radiologic imaging criteria.

The early stopping point is 21 subjects. If 10 or fewer subjects with tumor favorable response are observed when 21 subjects are accrued then the null hypothesis is accepted and the trial is terminated. If 16 or more subjects with tumor favorable response are observed when 21 subjects are accrued then the alternative hypothesis is accepted and the trial is terminated. The probability of early stopping under the null is 0.51, and under the alternative is 0.39. If the trial progresses until 42 subjects are evaluated and 24 or more subjects with favorable response are observed then the null hypothesis is rejected. This design minimizes the average sample number under the null, which is 31.2.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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)
- ALT and AST ≤ 2.5 times the ULN ( ≤ 5 x ULN for patients with liver involvement)
- Creatinine ≤ 1.5 times the ULN
International normalized ratio (INR) < 1.5 or a Prothrombin (PT)/Partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
ECOG performance status ≤ 2
Baseline left ventricular ejection fraction (LVEF) ≥ 50%
Life expectancy ≥ 3 months
Patients must agree to use adequate contraception prior to study entry, during the study and for at least three months after the last administration of sorafenib

Exclusion Criteria:

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
Evidence or history of bleeding diathesis or coagulopathy
Use of St. John's Wort or rifampin
Known or suspected allergy to sorafenib or any agent given in the course of this trial
Any condition that impairs patient's ability to swallow whole pills
Any malabsorption problem

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00452387

Locations

United States, California
Wilshire Oncology Medical Group, Inc.
La Verne, California, United States, 91750
United States, Georgia
Peachtree Hematology Oncology Consultants
Atlanta, Georgia, United States, 30309
Central Georgia Cancer Care
Macon, Georgia, United States, 31201
Northwest Georgia Oncology Centers
Marietta, Georgia, United States, 30060
United States, Montana
Hematology Oncology Centers of the Northern Rockies, PC
Billings, Montana, United States, 59101
United States, Ohio
Mid-Ohio Oncology/Hematology, Inc.
Columbus, Ohio, United States, 43213
United States, Pennsylvania
Lancaster Cancer Center
Lancaster, Pennsylvania, United States, 17605
Pennsylvania Oncology Hematmology Associates
Philadelphia, Pennsylvania, United States, 19106
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
United States, Virginia
Cancer Specialists of Tidewater
Chesapeake, Virginia, United States, 23320

Sponsors and Collaborators

Accelerated Community Oncology Research Network

Bayer

Investigators

Principal Investigator:

Vasily Assikis, MD

Peachtree Hematology Oncology Consultants

More Information

No publications provided

Responsible Party:	Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:	NCT00452387 History of Changes
Other Study ID Numbers:	ACORN AVAHRPC0607
Study First Received:	March 26, 2007
Results First Received:	August 17, 2009
Last Updated:	September 13, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Accelerated Community Oncology Research Network:

Prostate Cancer

Additional relevant MeSH terms:

Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Sorafenib
Mitoxantrone
Prednisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012