Prostate CancerPhase 1NCT00059631
Phase I Study of Weekly Intravenous PS-341 (Bortezomib) Plus Mitoxantrone
A Phase 1 study testing Mitoxantrone (Novantrone) and Bortezomib (PS-341) in people with Prostate Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary Objective: -Establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly mitoxantrone in combination with weekly PS-341 in patients with advanced AI-PCa. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Mitoxantrone (Novantrone) and Bortezomib (PS-341)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Mar 2003to 17 Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patient has given voluntary written informed consent before performance of any study-related procedure not part of standard medical care.
- Patient has histologically-confirmed advanced and/or metastatic AI-PCa requiring anti-neoplastic treatment. Patients should continue on LHRH analog therapy throughout the study period, if this is their mode of androgen suppression therapy. Patients should have discontinued anti-androgen therapy for >/= than 4 weeks (for flutamide) or >/= 6 weeks (for bicalutamide and nilutamide).
- Patient has progressive measurable or evaluable disease, defined as meeting at least one of the three criteria, described in protocol section 4.1.
- Zubrod performance status of </= 2 (Appendix B).
- Resting Left Ventricular Ejection Fraction (LEVF) >/= 50%.
- Patient has all of the following pretreatment laboratory data within 14 days (except for serum testosterone which may be done within 28 days prior to registration) before the first study drug dose: Absolute neutrophil count (ANC) >/= 1,500/mm^3. Platelets >/= 100,000/mm^3. Hemoglobin >8.0 g/dL. Total bilirubin </=1.5 x the upper limit of normal (ULN). ALT or AST </= 2.5 x the ULN, or, if the patient has liver metastases, </= 5 x the ULN. Creatinine </= 2 mg/dL. Serum testosterone </= 50 ng/mL.
Who cannot join
- Patient has received chemotherapy (including thalidomide or ketoconazole) within four weeks, nitrosoureas within six weeks, or antibody therapy within eight weeks of enrollment.
- Patient has received radiation therapy or Samarium-153 within four weeks of enrollment, or Strontium-89 within 12 weeks of enrollment.
- Patient has not recovered from all serious toxic effects of previous chemotherapy or radiation or antibody therapy.
- Patient received treatment with flutamide within four weeks of enrollment or nilutamide or bicalutamide within six weeks of enrollment.
- Patient has had any major surgery within four weeks of enrollment.
- Patient has a history of allergic reactions to anti-diarrheal medications or anti-emetics suggested to be administered in conjunction with study drug (see Section 5.1.4.1).
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- Patient has a history of severe hypersensitivity reaction to mitoxantrone or other agents formulated with polysorbate 80.
- Patients with significant atherosclerotic disease, as defined by: a) myocardial infarction within six months of enrollment, uncontrolled / unstable angina pectoris or electrocardiographic evidence of acute ischemia b) clinically significant ventricular arrhythmias, c) symptomatic congestive heart failure d) significant conduction abnormalities: 2nd or 3rd degree AV blocks, bifascicular block (defined as Left Anterior Hemiblock in the presence of Right Bundle Branch Block), e) claudication limiting activity and f) history of cerebrovascular events within the last year (including TIA)
- Patients who have received > equivalent to 180 mg/m^2 of Doxorubicin cumulative dose.
- Patients with diabetes mellitus requiring insulin, or those that have required pharmacologic intervention for diabetes mellitus for greater than 5 years
- Patient has uncontrolled brain metastases or central nervous system disease.
- Patient has >/= Grade 2 peripheral neuropathy (per NCI CTC v.2).
- Patient has an uncontrolled intercurrent illness (e.g., active infection).
- Patient has another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the patient's ability to provide informed consent or with the completion of treatment according to this protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I Study of Weekly Intravenous PS-341 (Bortezomib) Plus Mitoxantrone in Patients With Advanced Androgen-Independent Prostate Cancer (AI-PCa)
Primary Objective:
-Establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly mitoxantrone in combination with weekly PS-341 in patients with advanced AI-PCa.
Secondary objectives:
- Evaluate the effect of bortezomib and mitoxantrone in combination on PSA levels among patients with baseline PSA levels >/=5 ng/mL who are treated near the maximum tolerated dose.
- Monitor the effect of escalating doses of bortezomib combined with mitoxantrone on selected parameters of clinical benefit (i.e. performance status, tumor-related symptoms, measurable disease response).
Read the detailed description
Mitoxantrone is used to treat bone pain in advanced prostate cancer and inhibits many proteins that the cancer cells need to multiply.
Bortezomib is a member of a new class of drugs that possess powerful and broad-spectrum anti-tumor activity and inhibit many proteins that the cancer cells need to survive and multiply.
Pre-study testing will include brief physical examination, vital signs (weight, height, temperature, pulse, respiratory and blood pressure), chest x-ray, EKG (test to measure the electrical activity of the heart), echocardiogram, blood test, urine tests, and depending on the stage of the disease, a CT scan and/or bone scan.
During treatment, the participants will receive one dose of Mitoxantrone combined with one dose of Bortezomib every week for 4 weeks in a row followed by 2 weeks of rest; this is called a course. If side effects are not too severe, Mitoxantrone and Bortezomib will be infused rapidly into a vein while participants will be receiving normal saline ("salt in water solution") at a rate of 100ml/hour. They will receive the salt solution the entire time they are in the treatment area.
Participants will have their vital signs (temperature, pulse, breathing, blood pressure) taken before and one hour after treatment. All side effects during course one will be reviewed and, if no serious side effects took place, the participant may have additional courses. A pill may be given by mouth every day to decrease the risk of clot formation or a pill for diarrhea, nausea, and/or vomiting if the doctor believes that participants may need it.
Also during treatment, participants will have a complete physical examination by a physician or their designated representative (such as a nurse or physician assistant) each week of treatment. Bone Scan and/or CT Scan will be done if necessary. Participants will have blood tests done every week during study. A special blood test, called the 20S proteosome, will be done weekly during Cycles 1 and 2 to evaluate the activity of the drugs. Blood will be collected before you receive treatment and then at 1-2 hours afterward. About 2 teaspoons of blood will be collected each time for this. Bone scan, chest x-ray and/or CT scans will be repeated during the study every other course.
Participants will be taken off study if the disease gets worse or intolerable side effects occur. Side effects that are thought to be related to the study drug are renal failure resulting in death, and a grade 3 rash requiring treatment with steroids that recurred with subsequent treatments.
The maximum amount of time that participants can remain on the study is 8 courses of treatment. Long term follow-up of participants will include a phone call every 6 months.
This is an investigational study. Bortezomib has been approved by the FDA for investigational use only. Mitoxantrone has been approved by the FDA for treatment of symptoms in advanced prostate cancer. Only Mitoxantrone is commercially available. About 42 participants will take part in this study. All will be enrolled at M.D. Anderson .
- Conditions
- Prostate Cancer
- Being tested
- Mitoxantrone (Novantrone), Bortezomib (PS-341)
- Keywords
- Prostate Cancer, Advanced Androgen-Independent Prostate Cancer, AI-PCa, Advanced Prostate Cancer, Novantrone, Mitoxantrone, PS-341, Bortezomib, Velcade, LDP-341, MLN341, 20S proteasome
- 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 (Novantrone)Drug
Starting dose of 3 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15 and 22) over eight 5 week cycles.
Bortezomib (PS-341)Drug
Also called Velcade, LDP-341, MLN341
Starting Dose of 1.4 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15, and 22) over eight 5 week cycles.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib + Mitoxantrone | Experimental | Bortezomib starting dose of 1.4 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15, and 22) over eight 5 week cycles.
Mitoxantrone starting dose of 3 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15 and 22) over eight 5 week cycles. Receives: Drug: Mitoxantrone (Novantrone); Drug: Bortezomib (PS-341) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Novantrone (Mitoxantrone) combined with PS-341 (Bortezomib)
A single-course MTD is defined as the dose level having mean posterior dose limiting toxicity probability closest to 25%.
Measured: Continual reassessment method, with each 5 week cycle
Secondary outcomes (1)
Activity of drug's biochemical target, the 20S proteasome, in peripheral blood white cells
Measured: 7 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2003 (estimated)
- Study start20 Mar 2003
- Primary completion17 Jun 2015
- Study completion17 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Arlene Siefker-Radtke, MD, Principal investigator, UT M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00059631
- Sponsor's protocol ID
- ID02-227
- Other IDs
- P50CA090270, P30CA016672, MDA-ID-02227, CDR0000355822
- Status last verified
- Nov 2018
- First submitted
- 29 Apr 2003
- Last updated
- 15 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Weekly Intravenous PS-341 (Bortezomib) Plus Mitoxantrone in Patients With Advanced Androgen-Independent Prostate Cancer (AI-PCa)
- ClinicalTrials.gov ID
- NCT00059631
- Acronym / sponsor ID
- ID02-227
- Conditions
- Prostate Cancer
- Keywords
- Prostate Cancer, Advanced Androgen-Independent Prostate Cancer, AI-PCa, Advanced Prostate Cancer, Novantrone, Mitoxantrone, PS-341, Bortezomib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., National Cancer Institute (NCI)
- Study start
- 20 Mar 2003 (actual)
- Primary completion
- 17 Jun 2015 (actual)
- Study completion
- 17 Jun 2015 (actual)
- First posted
- 30 Apr 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
-Establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly mitoxantrone in combination with weekly PS-341 in patients with advanced AI-PCa.
Secondary objectives:
- Evaluate the effect of bortezomib and mitoxantrone in combination on PSA levels among patients with baseline PSA levels >/=5 ng/mL who are treated near the maximum tolerated dose.
- Monitor the effect of escalating doses of bortezomib combined with mitoxantrone on selected parameters of clinical benefit (i.e. performance status, tumor-related symptoms, measurable disease response).
Detailed description
Mitoxantrone is used to treat bone pain in advanced prostate cancer and inhibits many proteins that the cancer cells need to multiply.
Bortezomib is a member of a new class of drugs that possess powerful and broad-spectrum anti-tumor activity and inhibit many proteins that the cancer cells need to survive and multiply.
Pre-study testing will include brief physical examination, vital signs (weight, height, temperature, pulse, respiratory and blood pressure), chest x-ray, EKG (test to measure the electrical activity of the heart), echocardiogram, blood test, urine tests, and depending on the stage of the disease, a CT scan and/or bone scan.
During treatment, the participants will receive one dose of Mitoxantrone combined with one dose of Bortezomib every week for 4 weeks in a row followed by 2 weeks of rest; this is called a course. If side effects are not too severe, Mitoxantrone and Bortezomib will be infused rapidly into a vein while participants will be receiving normal saline ("salt in water solution") at a rate of 100ml/hour. They will receive the salt solution the entire time they are in the treatment area.
Participants will have their vital signs (temperature, pulse, breathing, blood pressure) taken before and one hour after treatment. All side effects during course one will be reviewed and, if no serious side effects took place, the participant may have additional courses. A pill may be given by mouth every day to decrease the risk of clot formation or a pill for diarrhea, nausea, and/or vomiting if the doctor believes that participants may need it.
Also during treatment, participants will have a complete physical examination by a physician or their designated representative (such as a nurse or physician assistant) each week of treatment. Bone Scan and/or CT Scan will be done if necessary. Participants will have blood tests done every week during study. A special blood test, called the 20S proteosome, will be done weekly during Cycles 1 and 2 to evaluate the activity of the drugs. Blood will be collected before you receive treatment and then at 1-2 hours afterward. About 2 teaspoons of blood will be collected each time for this. Bone scan, chest x-ray and/or CT scans will be repeated during the study every other course.
Participants will be taken off study if the disease gets worse or intolerable side effects occur. Side effects that are thought to be related to the study drug are renal failure resulting in death, and a grade 3 rash requiring treatment with steroids that recurred with subsequent treatments.
The maximum amount of time that participants can remain on the study is 8 courses of treatment. Long term follow-up of participants will include a phone call every 6 months.
This is an investigational study. Bortezomib has been approved by the FDA for investigational use only. Mitoxantrone has been approved by the FDA for treatment of symptoms in advanced prostate cancer. Only Mitoxantrone is commercially available. About 42 participants will take part in this study. All will be enrolled at M.D. Anderson .
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib + Mitoxantrone | Experimental | Drug: Mitoxantrone (Novantrone), Drug: Bortezomib (PS-341)Bortezomib starting dose of 1.4 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15, and 22) over eight 5 week cycles. Mitoxantrone starting dose of 3 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15 and 22) over eight 5 week cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient has given voluntary written informed consent before performance of any study-related procedure not part of standard medical care.
- Patient has histologically-confirmed advanced and/or metastatic AI-PCa requiring anti-neoplastic treatment. Patients should continue on LHRH analog therapy throughout the study period, if this is their mode of androgen suppression therapy. Patients should have discontinued anti-androgen therapy for >/= than 4 weeks (for flutamide) or >/= 6 weeks (for bicalutamide and nilutamide).
- Patient has progressive measurable or evaluable disease, defined as meeting at least one of the three criteria, described in protocol section 4.1.
- Zubrod performance status of </= 2 (Appendix B).
- Resting Left Ventricular Ejection Fraction (LEVF) >/= 50%.
Key exclusion criteria (14 listed)
- Patient has received chemotherapy (including thalidomide or ketoconazole) within four weeks, nitrosoureas within six weeks, or antibody therapy within eight weeks of enrollment.
- Patient has received radiation therapy or Samarium-153 within four weeks of enrollment, or Strontium-89 within 12 weeks of enrollment.
- Patient has not recovered from all serious toxic effects of previous chemotherapy or radiation or antibody therapy.
- Patient received treatment with flutamide within four weeks of enrollment or nilutamide or bicalutamide within six weeks of enrollment.
- Patient has had any major surgery within four weeks of enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitoxantrone (Novantrone)Starting dose of 3 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15 and 22) over eight 5 week cycles. | Drug | Bortezomib + Mitoxantrone |
| Bortezomib (PS-341)Also: Velcade, LDP-341, MLN341Starting Dose of 1.4 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15, and 22) over eight 5 week cycles. | Drug | Bortezomib + Mitoxantrone |
Primary outcome
Maximum Tolerated Dose (MTD) of Novantrone (Mitoxantrone) combined with PS-341 (Bortezomib)
Time frame: Continual reassessment method, with each 5 week cycle
A single-course MTD is defined as the dose level having mean posterior dose limiting toxicity probability closest to 25%.
1 secondary outcome
Activity of drug's biochemical target, the 20S proteasome, in peripheral blood white cells
Time frame: 7 Years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arlene Siefker-Radtke, MD principal investigator
UT M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mitoxantrone (Novantrone) and Bortezomib (PS-341) in people with Prostate Cancer, run by M.D. Anderson Cancer Center at 1 site 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 6 inclusion and 14 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 15 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose (MTD) of Novantrone (Mitoxantrone) combined with PS-341 (Bortezomib) (time frame: Continual reassessment method, with each 5 week cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Nov 2018.