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Metastatic Prostate CancerPhase 2NCT00452387

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

A Phase 2 study testing Mitoxantrone, Prednisone and Sorafenib in people with Metastatic Prostate Cancer, run by Accelerated Community Oncology Research Network at 10 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Metastatic Prostate Cancer
What is being tested?
Mitoxantrone, Prednisone and Sorafenib
How many people
22 participants
Where
10 sitesUnited States
Study dates
May 2007to Jan 2009
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 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 22Show fewer
  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Peachtree Hematology Oncology Consultants

    Atlanta, Georgia, 30309

  • Hematology Oncology Centers of the Northern Rockies, PC

    Billings, Montana, 59101

  • Cancer Specialists of Tidewater

    Chesapeake, Virginia, 23320

  • Mid-Ohio Oncology/Hematology, Inc.

    Columbus, Ohio, 43213

  • Wilshire Oncology Medical Group, Inc.

    La Verne, California, 91750

  • Lancaster Cancer Center

    Lancaster, Pennsylvania, 17605

  • Central Georgia Cancer Care

    Macon, Georgia, 31201

  • Northwest Georgia Oncology Centers

    Marietta, Georgia, 30060

  • The West Clinic

    Memphis, Tennessee, 38120

  • Pennsylvania Oncology Hematmology Associates

    Philadelphia, Pennsylvania, 19106

Other trials in United States

About this study

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.

Read the 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.

Being tested
Mitoxantrone, Prednisone, Sorafenib
Keywords
Prostate Cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MitoxantroneDrug

    Also called 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, Mitoxantrone 9mg/m2

    Dose Level -1 Mitoxantrone 12mg/m2

    Dose Level 1 Mitoxantrone 12mg/m2

  • PrednisoneDrug

    Also called 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, Prednisone 5mg bid

    Dose Level -1 Prednisone 5mg bid

    Dose Level 1 Prednisone 5mg bid

  • SorafenibDrug

    Also called Nexavar

    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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (3)

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

    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.

    Measured: 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.

  2. Quality of Life (QoL)

    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.

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

  3. Median Overall Survival (OS)

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionJul 2008
  4. Study completionJan 2009

Why it stopped: Early stopping rule

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00452387
Sponsor's protocol ID
ACORN AVAHRPC0607
Status last verified
Sep 2011
First submitted
26 Mar 2007
Last updated
16 Sep 2011
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mitoxantrone, Prednisone and Sorafenib in people with Metastatic Prostate Cancer, run by Accelerated Community Oncology Research Network at 10 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 22 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: stopped early, as of the sponsor's last update on 16 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 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 26 May 2010). 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?

Median Time to Progression (TTP) by Imaging (time frame: Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00452387.

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 16 Sep 2011.

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