Prostate CancerPhase 1/2NCT00471718
ABT-751 in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
A Phase 1/2 study testing ABT-751 in people with Prostate Cancer, run by Vanderbilt-Ingram Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-751 and to see how well it works in treating patients with… 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?
- ABT-751
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Aug 2009
- 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
- Patients at least 18 years of age.
- Patients must have histologically proven adenocarcinoma of the prostate gland.
- Patients must have metastatic disease (e.g. bone metastases, pelvic mass, nodal, liver or lung metastases), with evidence of radiographic progression (including bone scans observed during last treatment) or serologically -Patients with bone-only metastases (i.e. lacking soft tissue or visceral disease) must have a PSA level > 10 ng/mls. Patients with soft tissue metastases and/or visceral disease must have either measurable disease OR a PSA level > 10 ng/ml.
- Patients must have had prior treatment with bilateral orchiectomy or other primary hormonal therapy (e.g. LHRH therapy, estrogens, etc.) with evidence of treatment failure and simultaneous documentation of a castrate testosterone level (< 50 ng/dL) NOTE: Patients who have not undergone bilateral orchiectomy must continue LHRH agonist therapy for the duration of this protocol unless this medically contraindicated.
- For patients previously treated with flutamide, nilutamide, or bicalutamide: patients must have discontinued flutamide or nilutamide > 4 weeks prior to randomization (> 6 weeks for bicalutamide) with no evidence of an anti-androgen withdrawal response (i.e. no decline in serum PSA and/or no improvement in baseline scans).
- Patients must have received prior therapy with docetaxel alone or in combination with either prednisone or estramustine. This therapy may have been given in a neoadjuvant, adjuvant or metastatic setting
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- Patients must not have received radiotherapy < 3 weeks prior to randomization. If patients have received prior radiotherapy to an evaluable lesion(s), there must be evidence of radiographic progression prior to entry.
- Patients must not have received prior Strontium 89, Samarium 153, or other therapeutic radioisotopes.
- Patients must have recovered from all systemic toxicities due to prior treatment for prostate cancer (does not include incontinence, impotence, etc. secondary to primary therapy)
- The patient must have an ECOG Performance Status of 0-1
- The patient must have adequate hematologic, renal and hepatic function as follows:
- Hematologic: ANC > 1200/mm3; hemoglobin > 9.0 g/dl; platelets > 100,000/mm3
- Renal: serum creatinine < 2.0 mg/dL
- Hepatic: bilirubin < 2.5 mg/dL; AST and ALT < 2.5X upper limit of normal (ULN); < 5X ULN for patients with hepatic metastases
- Sexually-active patients must use a contraceptive method deemed acceptable by the investigator while in the study and for up to 3 months following completion of therapy.
- The patient or the patient's legally acceptable representative has voluntarily signed and dated an informed consent approved by and Institutional Review Board prior to any study any study specific procedures.
- Patients may be receiving bisphosphonate therapy prior to randomization and continue while receiving protocol therapy, but must not begin treatment with bispohosphonates while receiving protocol therapy. Patients on bisphosphonates must have completed at least 4 weeks of bisphosphonate therapy prior to entry onto study.
- Patients with a history of a prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for the specific malignancy.
Who cannot join
- No active angina pectoris, uncontrolled hypertension, or known heart disease of New York Heart Association Class III-IV. Patients must not have a history of myocardial infarction, congestive cardiac failure (New York Heart Association Class 3), or coronary angioplasty/stenting < 6 months prior to entry.
- No carcinomatous meningitis or brain metastases.
- Any investigational therapy within 4 weeks.
- No serious concurrent medical illness or active infection, which, in the opinion of the investigator, would jeopardize the ability of the patient to receive the chemotherapy outlined in this protocol with reasonable safety.
- Documented history of allergy to sulfa medications.
- Current colchicines treatment
- Greater than Grade 1 CTC neurology category findings (Appendix A).
- Prior treatment with more than 1 prior chemotherapy regimen.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: A Phase1/2 Trial of ABT-751 in Patients With Advanced, Androgen-Independent Prostate Cancer
RATIONALE: Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-751 and to see how well it works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.
Read the detailed description
OBJECTIVES:
Primary
- Evaluate the safety and efficacy of ABT-751 in patients with androgen-independent, hormone-refractory metastatic prostate cancer and determine the maximum tolerated dose (MTD) and optimal phase II dose of this drug in these patients.
Secondary
- Determine the objective response rate (partial and complete response) in patients with measurable disease treated with this drug.
- Evaluate the effect of this drug on prostate-specific antigen (PSA) response in patients with nonmeasurable disease.
- Determine the time to tumor progression in patients treated with this drug.
- Determine survival of patients treated with this drug.
- Determine the toxicity of this drug in these patients.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ABT-751 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 50 additional patients may be treated at the recommended phase II dose (RPTD) which is the dose level at the maximally administered dose.
- Phase II: Patients receive ABT-751 at the MTD determined in phase I. After completion of study treatment, patients are followed every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
- Conditions
- Prostate Cancer
- Being tested
- ABT-751
- Keywords
- adenocarcinoma of the prostate, stage IV prostate cancer, recurrent 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.
ABT-751Drug
Phase I:
Cohort | Number of Patients |Dose (mg) ABT-751 (BID)
- -1 | 3-6 |100 mg BID
- 1 | 3-6 |125 mg BID
- 2 | 3-6 |150 mg BID
- 3 | 3-6 |175 mg BID
- 4 | 3-6 |200 mg BID
Phase II:
Patients receive ABT-751 at 125mg po BID for 7 days on, 7 days off (X2) for a 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Phase I/II: Chemotherapy ABT-751 | Experimental | Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21.
Phase II: Patients receive ABT-751 twice daily Receives: Drug: ABT-751 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
MTD is determined by the 3+3 study design, in which patients are enrolled in cohorts of 3. In any dose cohort, if 1 patient of 3 experience dose-limiting toxicity (DLT), three additional patients will be enrolled at the same dose level. Whenever >=2 of 6 subjects experience a DLT, then the maximum tolerated dose (MTD) has been exceeded. The MTD is generally one dose below that at which DLT occurs in >= 2 of 6 subjects in any given cohort.
Measured: up to four weeks
Number of Patients Who Demonstrated Treatment Effectiveness Based on Prostate Specific Antigen (PSA) Response in Non-measurable Disease
Patients with a minimum 50% decline in PSA from pre-treatment baseline, confirmed by a second PSA 4 or more weeks later, measured in nanograms per milliliter of blood.
Measured: after four weeks
Secondary outcomes (4)
Number of Patients With Objective Response (CR & PR) by RECIST
Number of participants in each best tumor response category, RECIST criteria (v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in sum longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in sum LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of smallest sum of the LD of target lesions.
Measured: after four weeks
Median Time to Tumor Progression
Number of weeks from the date the patient started study drug to the date of the patient's tumor progression documented radiographically or by PSA testing.
Tumor progression is measured at baseline and after two 28-day cycles
Measured: date on study to date of progression
Overall Survival
Number of weeks from the date the patient started study drug to the date of the patient's death.
Measured: date on study to date of death from any cause
Safety Profile Based on Number of Patients With Worst Grade Toxicities
Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening or disabling, grade 5 = death)following NCI Common Toxicity Criteria
Measured: at 30 days after final treatment dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2007 (estimated)
- Study startJan 2004
- Primary completionAug 2009
- Study completionAug 2009
Why it stopped: pharmaceutical company closed study because the treatment was not effective
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Jeffrey A. Sosman, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Jeff Sosman, MD, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00471718
- Sponsor's protocol ID
- VICC URO 0426
- Other IDs
- VU-VICC-URO-0426
- Status last verified
- Jun 2012
- First submitted
- 8 May 2007
- Last updated
- 11 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase1/2 Trial of ABT-751 in Patients With Advanced, Androgen-Independent Prostate Cancer
- ClinicalTrials.gov ID
- NCT00471718
- Acronym / sponsor ID
- VICC URO 0426
- Conditions
- Prostate Cancer
- Keywords
- adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: pharmaceutical company closed study because the treatment was not effective
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2004
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 10 May 2007 (estimated)
- Results
- Posted 27 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-751 and to see how well it works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.
Detailed description
OBJECTIVES:
Primary
- Evaluate the safety and efficacy of ABT-751 in patients with androgen-independent, hormone-refractory metastatic prostate cancer and determine the maximum tolerated dose (MTD) and optimal phase II dose of this drug in these patients.
Secondary
- Determine the objective response rate (partial and complete response) in patients with measurable disease treated with this drug.
- Evaluate the effect of this drug on prostate-specific antigen (PSA) response in patients with nonmeasurable disease.
- Determine the time to tumor progression in patients treated with this drug.
- Determine survival of patients treated with this drug.
- Determine the toxicity of this drug in these patients.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ABT-751 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 50 additional patients may be treated at the recommended phase II dose (RPTD) which is the dose level at the maximally administered dose.
- Phase II: Patients receive ABT-751 at the MTD determined in phase I. After completion of study treatment, patients are followed every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I/II: Chemotherapy ABT-751 | Experimental | Drug: ABT-751Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Phase II: Patients receive ABT-751 twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients at least 18 years of age.
- Patients must have histologically proven adenocarcinoma of the prostate gland.
- Patients must have metastatic disease (e.g. bone metastases, pelvic mass, nodal, liver or lung metastases), with evidence of radiographic progression (including bone scans observed during last treatment) or serologically -Patients with bone-only metastases (i.e. lacking soft tissue or visceral disease) must have a PSA level > 10 ng/mls. Patients with soft tissue metastases and/or visceral disease must have either measurable disease OR a PSA level > 10 ng/ml.
- Patients must have had prior treatment with bilateral orchiectomy or other primary hormonal therapy (e.g. LHRH therapy, estrogens, etc.) with evidence of treatment failure and simultaneous documentation of a castrate testosterone level (< 50 ng/dL) NOTE: Patients who have not undergone bilateral orchiectomy must continue LHRH agonist therapy for the duration of this protocol unless this medically contraindicated.
- For patients previously treated with flutamide, nilutamide, or bicalutamide: patients must have discontinued flutamide or nilutamide > 4 weeks prior to randomization (> 6 weeks for bicalutamide) with no evidence of an anti-androgen withdrawal response (i.e. no decline in serum PSA and/or no improvement in baseline scans).
Key exclusion criteria (8 listed)
- No active angina pectoris, uncontrolled hypertension, or known heart disease of New York Heart Association Class III-IV. Patients must not have a history of myocardial infarction, congestive cardiac failure (New York Heart Association Class 3), or coronary angioplasty/stenting < 6 months prior to entry.
- No carcinomatous meningitis or brain metastases.
- Any investigational therapy within 4 weeks.
- No serious concurrent medical illness or active infection, which, in the opinion of the investigator, would jeopardize the ability of the patient to receive the chemotherapy outlined in this protocol with reasonable safety.
- Documented history of allergy to sulfa medications.
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 |
|---|---|---|
| ABT-751Phase I: Cohort | Number of Patients |Dose (mg) ABT-751 (BID) * -1 | 3-6 |100 mg BID * 1 | 3-6 |125 mg BID * 2 | 3-6 |150 mg BID * 3 | 3-6 |175 mg BID * 4 | 3-6 |200 mg BID Phase II: Patients receive ABT-751 at 125mg po BID for 7 days on, 7 days off (X2) for a 28 day cycle | Drug | Phase I/II: Chemotherapy ABT-751 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: up to four weeks
MTD is determined by the 3+3 study design, in which patients are enrolled in cohorts of 3. In any dose cohort, if 1 patient of 3 experience dose-limiting toxicity (DLT), three additional patients will be enrolled at the same dose level. Whenever >=2 of 6 subjects experience a DLT, then the maximum tolerated dose (MTD) has been exceeded. The MTD is generally one dose below that at which DLT occurs in >= 2 of 6 subjects in any given cohort.
Number of Patients Who Demonstrated Treatment Effectiveness Based on Prostate Specific Antigen (PSA) Response in Non-measurable Disease
Time frame: after four weeks
Patients with a minimum 50% decline in PSA from pre-treatment baseline, confirmed by a second PSA 4 or more weeks later, measured in nanograms per milliliter of blood.
4 secondary outcomes
Number of Patients With Objective Response (CR & PR) by RECIST
Time frame: after four weeks
Median Time to Tumor Progression
Time frame: date on study to date of progression
Overall Survival
Time frame: date on study to date of death from any cause
Safety Profile Based on Number of Patients With Worst Grade Toxicities
Time frame: at 30 days after final treatment dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jeff Sosman, MD principal investigator
Vanderbilt-Ingram 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 1/2 study testing ABT-751 in people with Prostate Cancer, run by Vanderbilt-Ingram 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 18 inclusion and 8 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 11 Jul 2012. 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 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 27 Jun 2012). 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?
Maximum Tolerated Dose (MTD) (time frame: up to four weeks). The study lists 2 primary outcomes in all. 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 11 Jul 2012.