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Adenocarcinoma of the ProstatePhase 1/2NCT00331344

Treating Patients With Metastatic Prostate Cancer Not Responding to Hormone and Chemotherapy

A Phase 1/2 study testing mitoxantrone hydrochloride, ixabepilone and prednisone in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I/II trial is studying the side effects and best dose of ixabepilone and mitoxantrone hydrochloride when given together with prednisone and to see how well they work in treating patients with metastatic prostate cancer that did not respond to hormone therapy and chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
mitoxantrone hydrochloride, ixabepilone and prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
2 sitesUnited States
Study dates
Apr 2006to Nov 2010
Phase
Phase 1/2
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

  • Histologically confirmed adenocarcinoma of the prostate
  • Progressive metastatic disease (i.e., positive bone scan or measurable disease) despite castrate levels of testosterone (either from orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonist therapy)
  • Progressive disease after discontinuing hormonal therapy
  • Progressive disease is based on any of the following*:
  • Transaxial imaging
  • Rise in prostate-specific antigen (PSA)
Show all 47Show fewer
  • Radionuclide bone scan (must show new metastatic lesions)
  • Nonmeasurable or measurable disease
  • For measurable disease, progression is defined by RECIST criteria
  • Positive bone scan and elevated PSA required for nonmeasurable disease
  • PSA evidence of progressive prostate cancer during or after first-line chemotherapy consists of a PSA level ≥ 2 ng/mL that has risen on ≥ 2 successive occasions ≥ 1 week apart
  • Received ≥ 3 prior courses of paclitaxel- or docetaxel-based therapy, with disease progression documented during therapy or after cessation of therapy
  • No more than 1 prior chemotherapy regimen
  • Re-treatment with the same taxane-based regimen allowed
  • Changes in prior chemotherapy regimen (addition of other agents) for disease progression are considered 2 chemotherapy regimens, and are not allowed
  • PSA ≥ 2 ng/mL
  • Testosterone < 50 ng/dL
  • Patients must continue primary androgen deprivation with LHRH analogue if they have not undergone orchiectomy
  • No known active brain metastases
  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 40 mL/min
  • ALT and AST < 2.5 times ULN
  • Granulocyte count ≥ 2,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin < 1.5 times ULN
  • Ejection fraction normal by MUGA scan or echocardiogram
  • No significant cardiovascular disease, including any of the following:
  • Congestive heart failure (New York Heart Association class III-IV heart disease)
  • Active angina pectoris
  • Myocardial infarction within the past 6 months
  • No serious infections or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by study therapy
  • No psychiatric illness or social situation that would preclude study compliance
  • No pre-existing motor or sensory peripheral neuropathy > grade 1
  • No known prior severe hypersensitivity reactions to agents containing Cremophor® EL
  • No "currently active" second malignancy other than nonmelanoma skin cancer
  • Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered to be at < 30% risk of relapse
  • Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study treatment
  • See Disease Characteristics
  • No prior mitoxantrone hydrochloride, ixabepilone, or other epothilones
  • At least 4 weeks since prior hormonal therapy (i.e., any dose of megestrol, finasteride, or any herbal product known to decrease PSA levels [e.g., saw palmetto or PC-SPES]) other than LHRH agonist or a stable dose of corticosteroids from a prior chemotherapy regimen
  • More than 4 weeks since other prior systemic therapies for prostate cancer
  • At least 4 weeks since prior radiation therapy
  • More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium)
  • No concurrent moderate to strong CYP3A4 inhibitors
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent radiotherapy

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94143-0875

Other trials in United States

About this study

Official title: Phase I/II Trial of Epothilone Analog BMS-247550 (Ixabepilone), Mitoxantrone, and Prednisone in Hormone Refractory Prostate Cancer (HRPC) Patients Previously Treated With Chemotherapy

This phase I/II trial is studying the side effects and best dose of ixabepilone and mitoxantrone hydrochloride when given together with prednisone and to see how well they work in treating patients with metastatic prostate cancer that did not respond to hormone therapy and chemotherapy. Drugs used in chemotherapy, such as ixabepilone, mitoxantrone hydrochloride, and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) and dose-limiting toxicities of the combination of ixabepilone, mitoxantrone hydrochloride, and prednisone in patients with hormone-refractory metastatic prostate cancer that progressed during or after taxane-based chemotherapy. (Phase I) II. Assess the efficacy, as measured by reduction in prostate-specific antigen, of this regimen in these patients. (Phase II)

SECONDARY OBJECTIVES:

  1. Evaluate the overall safety of this regimen as second-line chemotherapy in these patients.

II. Evaluate the objective response rate in patients treated with this regimen.

OUTLINE: This is a multicenter, phase I, open label, dose-escalation study of mitoxantrone hydrochloride and ixabepilone followed by a phase II study.

PHASE I: Patients receive mitoxantrone hydrochloride intravenously (IV) over 30 minutes and ixabepilone IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of mitoxantrone hydrochloride and ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive mitoxantrone hydrochloride and ixabepilone at the MTD determined in phase I and prednisone as in phase I.

After completion of study treatment, patients are followed every 3 months.

Being tested
mitoxantrone hydrochloride, ixabepilone, prednisone
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • mitoxantrone hydrochlorideDrug

    Also called CL 232315, DHAD, DHAQ, Novantrone

    Given IV

  • ixabepiloneDrug

    Also called BMS-247550, epothilone B lactam, Ixempra

    Given IV

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given orally

Study groups in NCT00331344
Study groupRoleWhat they receive
Treatment (combination chemotherapy)ExperimentalPatients receive mitoxantrone hydrochloride IV over 30 minutes and ixabepilone IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: mitoxantrone hydrochloride; Drug: ixabepilone; Drug: prednisone

What is being measured

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

  1. Proportion Responding to Treatment With of the Combination of Ixabepilone and Mitoxantrone Hydrochloride With Prednisone in Hormone Refractory Prostate Cancer Patients Who Have Had Prior Taxane Chemotherapy Based Upon a PSA Decline of > 50% (Phase II)

    Descriptive statistics will be calculated to characterize the disease and treatment factors including the proportion responding with a 95% confidence interval. If accrual is completed and more than 15 of 58 patients show > 50% Prostate Specific Antigen (PSA) declines after 3 courses, then the null hypothesis of a 20% response proportion will be rejected. PSA declines for individual patients will be plotted in the form of a waterfall diagram of maximal PSA declines.

    58 patients were enrolled for phase II, two were ineligible so 56 patients were analyzed.

    Measured: Every 3 courses until cancer progression/excessive toxicity or death

  2. Safety of the Combination of Ixabepilone, Mitoxantrone Hydrochloride, and Prednisone in Patients With Hormone-refractory Metastatic Prostate Cancer That Progressed During or After Taxane-based Chemotherapy (Phase I)

    This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 for adverse event monitoring and reporting. The cumulative grade 3 or higher adverse events for all dose levels are noted below and in the table of adverse events.

    Measured: Every 21 days until cancer progression/excessive toxicity or death

  3. Dose Limiting Toxicities for Each Dose Level of Ixabepilone, Mitoxantrone Hydrochloride, and Prednisone in Patients With Hormone-refractory Metastatic Prostate Cancer That Progressed During or After Taxane-based Chemotherapy (Phase I).

    Cohorts of 3 patients will be enrolled at each dose level; if 1 dose limiting toxicity (DLT) is observed then the cohort will be expanded to 6 patients. If a second DLT is observed, the previous dose level will be considered the maximum tolerated dose (MTD). If all observed DLT are due to neuropathy (specific to ixabepilone), then we would consider the previous dose level of Ixabepilone the MTD for that drug, and escalate mitoxantrone hydrochloride as described above to a maximum dose of 12 mg/m^2. Toxicities will be tabulated by grade for each dose cohort and overall for all patients accrued to the phase I study.

    Measured: Course 1 (first 21 days)

Secondary outcomes (1)

  1. Time to Progression (Phase II)

    Measured from the start of protocol therapy until RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.0 progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: Every 3 months until cancer progression/excessive toxicity or death

Timeline

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

  1. First posted31 May 2006 (estimated)
  2. Study startApr 2006
  3. Primary completionNov 2010
  4. Study completionNov 2010

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 1/2
Primary purpose
Treatment
Intervention model
Sequential
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00331344
Sponsor's protocol ID
NCI-2009-00155
Other IDs
055513, CDR0000481121, N01CM62202
Status last verified
Oct 2017
First submitted
30 May 2006
Last updated
31 Oct 2017
Data monitoring committee
Yes

Publications

  • Rosenberg JE, Ryan CJ, Weinberg VK, Smith DC, Hussain M, Beer TM, Ryan CW, Mathew P, Pagliaro LC, Harzstark AL, Sharib J, Small EJ. Phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy: a study of the department of defense prostate cancer clinical trials consortium. J Clin Oncol. 2009 Jun 10;27(17):2772-8. doi: 10.1200/JCO.2008.19.8002. Epub 2009 Apr 6.

    PubMed 19349545

  • Harzstark AL, Rosenberg JE, Weinberg VK, Sharib J, Ryan CJ, Smith DC, Pagliaro LC, Beer TM, Liu G, Small EJ. Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: a phase 2 study of the Department Of Defense Prostate Cancer Clinical Trials Consortium. Cancer. 2011 Jun 1;117(11):2419-25. doi: 10.1002/cncr.25810. Epub 2010 Dec 29.

    PubMed 24048789

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing mitoxantrone hydrochloride, ixabepilone and prednisone in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 2 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 47 inclusion and 0 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 31 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 31 Oct 2017). 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?

Proportion Responding to Treatment With of the Combination of Ixabepilone and Mitoxantrone Hydrochloride With Prednisone in Hormone Refractory Prostate Cancer Patients Who Have Had Prior Taxane Chemotherapy Based Upon a PSA Decline of > 50% (Phase II) (time frame: Every 3 courses until cancer progression/excessive toxicity or death). The study lists 3 primary outcomes in all. 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 NCT00331344, which also lists 2 linked publications.

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 31 Oct 2017.

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