Metastatic Prostate Cancer
Conditions
Brief summary
The purpose of this research study is to find out what effects (good and bad) Sutent has on you and your prostate cancer.
Detailed description
The following rationale can be made for a Phase II trial to evaluate sunitinib malate (Sutent) for the therapy of progressive metastatic androgen-independent prostate cancer (AIPC) following prior docetaxel chemotherapy. Since most patients with metastatic AIPC following prior chemotherapy clinically progress rapidly, we believe that achieving a 30% freedom from clinical progression (PFS) (not including PSA progression) at 12 weeks represents biologically active therapy. Sunitinib malate (Sutent) represents a tolerable and convenient form of therapy with the potential for improving outcomes in AIPC.
Interventions
DRUGSunitinib
50 mg/day orally each of Days 1-28 of each 6 week cycle
Sponsors
Pfizer
US Oncology Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A patient will be eligible for inclusion in this study if he meets all of the following criteria: * Histologically confirmed, adenocarcinoma of the prostate * Stage IV(metastatic) disease, documented on CT, MRI, or X-ray * Progressive disease (PSA or clinical): PSA progression defined as baseline increase followed by any serial increase after 2 weeks; clinical progression by symptomatic or radiologic criteria. * An elevated PSA level of for patients progressing by PSA criteria is required * Currently on androgen ablation hormone therapy (an LHRH agonist or orchiectomy) with testosterone level \<50ng/dL) * Has received 1 or 2 prior chemotherapy regimens (no more than 2). One prior regimen must be docetaxel. * Has an ECOG Performance Status (PS) 0-2 * Is greater than 18 years of age * Meets protocol defined laboratory values * Has adequate cardiac function in the opinion of the Investigator * Has no uncontrolled arrhythmia or hypertension * Resolution of all acute toxic effects of prior chemotherapy or surgical procedures to NCI CTCAE Version 3.0 Grade less than 1, in the opinion of the Treating Physician * If fertile, patient has agreed to use an acceptable method of birth control to prevent pregnancy for the duration of the study and for a period of 2 months thereafter * Has signed a Patient Informed Consent Form * Has signed a Patient Authorization Form
Exclusion criteria
* A patient will be excluded from this study if he meets any of the following criteria: * Has any disease other than that described in inclusion criterion #1 * Had prior treatment with Sutent * Has not received prior docetaxel for the current disease * Has received any prior radionuclide therapy * Has received prior radiation to \>50% of the bone marrow * Is receiving concurrent immunotherapy * Has a history of hypersensitivity to any of the components of Sutent: mannitol, croscarmellose sodium, povidone (K-25) and magnesium stearate as inactive ingredients. The orange gelatin capsule shells contain titanium dioxide, and red iron oxide. The caramel gelatin capsule shells also contain yellow iron oxide and black iron oxide. The printing ink contains shellac, propylene glycol, sodium hydroxide, povidone and titanium dioxide. * Has had significant bleeding in previous 4 weeks * Has had any of the following within the prior 6 months: severe/unstable angina, myocardial infarction, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack, or pulmonary embolism * Is receiving concurrent bisphosphonate therapy; long-standing bisphosphonate therapy (initiated \>8 weeks prior to registration) is acceptable. Bisphosphonates started within the prior 8 weeks will not be allowed since this may affect other study endpoints and render their interpretation difficult * Has received treatment with radiation therapy, surgery, chemotherapy, ketoconazole, corticosteroids, or an investigational agent within 4 weeks prior to registration, (6 weeks for radiation therapy, nitrosureas or Mitomycin C) * Has uncontrolled arrhythmia or hypertension * Has evidence of uncontrolled CNS involvement (previous radiation and off steroids is acceptable) * Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication * Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection * Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin), which could affect the diagnosis or assessment of any of the study drugs * Is unable to comply with requirements of study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival (PFS) Time at 1-year. | 12 months | PFS is measured from the date of registration to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overal Survival (OS) Rate at 1-year. | 12 months | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. |
| Prostate Specific Antigen (PSA) Response | Baseline and up to 12 months | Percentage of participants whose PSA value declined to 50% when compared to the value at the baseline. |
| Change of PSA Doubling Time | Baseline and up to 12 months | Difference of PSA doubling time between baseline and end of the treatment. |
| Objective Response Rate (ORR) | 12 months | ORR = Complete Response (CR) + Partial response (PR). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. |
| Percentage of Participants With Decrease in Present Pain Intensity (PPI) From Baseline. | Baseline and up to 12 months | Pain score decreased \>=2 points from baseline. The PPI scale has the following descriptors: 0=no pain, 1=mild pain, 2=discomforting pain, 3=distressing pain, 4=horrible pain, and 5=excruciating pain. The patient will be asked to self-assess and record their PPI in the study diary. Upon diary review, the study nurse will utilize the PPI daily scores to calculate the week's average. The weekly PPI score during the study is the average of the daily PPI scores, based on a minimum of 3 daily PPI assessments during a week's period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Malate Sunitinib Malate (Sutent) (50 mg/day on Days 1-28 of 42-day cycles) | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 19 |
| Overall Study | Disease Progression | 12 |
| Overall Study | Ineligible | 1 |
| Overall Study | Patient Request | 4 |
Baseline characteristics
| Characteristic | Sunitinib Malate |
|---|---|
| Age, Continuous | 70.0 years STANDARD_DEVIATION 9.34 |
| Race/Ethnicity, Customized Black | 3 participants |
| Race/Ethnicity, Customized Caucasian | 32 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 35 |
| serious Total, serious adverse events | 7 / 35 |
Outcome results
Primary
Median Progression-free Survival (PFS) Time at 1-year.
PFS is measured from the date of registration to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.
Time frame: 12 months
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib Malate | Median Progression-free Survival (PFS) Time at 1-year. | 19.4 weeks |
Secondary
Change of PSA Doubling Time
Difference of PSA doubling time between baseline and end of the treatment.
Time frame: Baseline and up to 12 months
Population: Patients who had measurements of prior and post doubling time.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib Malate | Change of PSA Doubling Time | 0.5 months |
Secondary
Objective Response Rate (ORR)
ORR = Complete Response (CR) + Partial response (PR). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
Time frame: 12 months
Population: Only patients with baseline measurable lesions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Objective Response Rate (ORR) | 11.1 percentage of participants |
Secondary
Overal Survival (OS) Rate at 1-year.
OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Time frame: 12 months
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Overal Survival (OS) Rate at 1-year. | 0.42 Probability of Survival at 1-year |
Secondary
Percentage of Participants With Decrease in Present Pain Intensity (PPI) From Baseline.
Pain score decreased \>=2 points from baseline. The PPI scale has the following descriptors: 0=no pain, 1=mild pain, 2=discomforting pain, 3=distressing pain, 4=horrible pain, and 5=excruciating pain. The patient will be asked to self-assess and record their PPI in the study diary. Upon diary review, the study nurse will utilize the PPI daily scores to calculate the week's average. The weekly PPI score during the study is the average of the daily PPI scores, based on a minimum of 3 daily PPI assessments during a week's period.
Time frame: Baseline and up to 12 months
Population: Patients with pain measurement at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Percentage of Participants With Decrease in Present Pain Intensity (PPI) From Baseline. | 13.6 percentage of participants |
Secondary
Prostate Specific Antigen (PSA) Response
Percentage of participants whose PSA value declined to 50% when compared to the value at the baseline.
Time frame: Baseline and up to 12 months
Population: Evaluable population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Malate | Prostate Specific Antigen (PSA) Response | 12.1 percentage of participants |