Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer
Brief summary
RATIONALE: Monoclonal antibodies, such as anti-IL-6 chimeric monoclonal antibody, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well anti-IL-6 chimeric monoclonal antibody works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.
Detailed description
OBJECTIVES: Primary * Assess the confirmed prostate-specific antigen response in patients with hormone-refractory metastatic prostate cancer treated with anti-IL-6 chimeric monoclonal antibody. Secondary * Assess overall survival and progression-free survival of these patients. * Assess the objective response rate (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with this regimen. * Assess the qualitative and quantitative toxicities of this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive anti-IL-6 chimeric monoclonal antibody IV over 2 hours on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 2 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Interventions
Sponsors
Study design
Eligibility
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the prostate * Metastatic disease (N1 and/or M1) * Disease unresponsive or refractory to androgen-deprivation therapy * Must have received only 1 prior chemotherapy regimen comprising a taxane OR mitoxantrone * Disease progression as defined by one or more of the following: * Progression of measurable disease * Prior radiotherapy allowed provided radiotherapy was completed ≥ 2 months ago and lesion progressed since radiotherapy * Progression of nonmeasurable disease * Prior radiotherapy within the past 2 months allowed, but disease is considered nonmeasurable * Rising prostate-specific antigen (PSA) after \> 2 courses of chemotherapy OR within 6 months of last chemotherapy dose * Rising PSA defined as at least 2 consecutive rises in PSA to be documented over a reference value (measure 1) * PSA ≥ 5 ng/mL * Surgical or medical castration required * Castration using luteinizing hormone-releasing hormone agonist (leuprolide acetate or goserelin) or antagonist (abarelix) should not be interrupted * No history of brain metastases OR currently treated or untreated brain metastases * Patients with clinical suspicion of brain metastases must have a brain CT scan or MRI negative for metastatic disease within the past 56 days PATIENT CHARACTERISTICS: * Zubrod performance status 0-2 * Fertile patients must use effective contraception * Absolute granulocyte count ≥ 1,500/mm³ (transfusion independent) * Platelet count ≥ 100,000/mm³ (transfusion independent) * Hemoglobin ≥ 9 g/dL (transfusion independent) * Creatinine clearance ≥ 40 mL/min * Bilirubin ≤ 2 times upper limit of normal (ULN) * Aspartate aminotransferase (AST) ≤ 2 times ULN * No uncontrolled intercurrent illnesses including, but not limited to, the following: * Diabetes mellitus * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * No psychiatric illness or social situation that would preclude study compliance * No known HIV positivity * No other prior malignancy except for the following: * Adequately treated basal cell or squamous cell skin cancer * Adequately treated stage I or II cancer in complete remission * Any other cancer from which the patient has been disease-free for 5 years PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 21 days since prior surgery and recovered * At least 28 days since prior chemotherapy and recovered * At least 28 days since prior flutamide or ketoconazole * At least 28 days since prior radiotherapy (to \< 30% of the bone marrow only) and recovered * Prior samarium Sm 153 lexidronam pentasodium allowed * No prior strontium chloride Sr 89 * At least 42 days since prior bicalutamide or nilutamide * More than 60 days since prior murine or chimeric proteins or human/murine monoclonal antibody * Concurrent bisphosphonate therapy allowed provided the following are true: * Therapy commenced at least 3 weeks ago * Therapy continues for the entire duration of study treatment * No other concurrent anticancer therapy, including cytotoxic therapy, biologic therapy, radiotherapy, or hormonal therapy (except for luteinizing hormone-releasing hormone agonist or antagonist in patients who have not had an orchiectomy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Prostate-Specific Antigen (PSA) Response | Assessed every 3 cycles (1 cycle = 14 days) until progression | PSA response is defined as a 50% reduction in accordance with the recommendations of the orginal PSA Working Group. Confirmed PSA response is defined as PSA response at two or more time points at least 4 weeks apart, without objective disease progression or symptomatic deterioration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Assessed every 3 cycles (1 cycle = 14 days) until progression | PFS is defined as tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, PSA progression by PSA Working Group criteria, or symptomatic deterioration. |
| Overall Survival (OS) | 0-3 yeas after registration | Measured from date of registration to date of death due to any cause or last contact |
| Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | Assessed every 3 cycles (1 cycle= 14 days) of treatment until progression | Complete Response (CR) is a complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. PSA = .2 ng/ml. Partial Response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. |
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Patients were assessed for adverse events after every cycle (1 cycle = 14 days) of protocol treatment | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CNTO 328 CNTO 328 will be given 6 mg/kg through intravenous (IV) once per cycle ( 1 cycle= 14 days) for 12 cycles | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Ineligible | 9 |
| Overall Study | Other - Not Protocol specified | 3 |
| Overall Study | Progression | 44 |
| Overall Study | Refusal Unrelated to Adverse Event | 1 |
Baseline characteristics
| Characteristic | CNTO 328 |
|---|---|
| Age Continuous | 71 years |
| Baseline PSA (ng/dL) | 75.1 ng/dL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Performance Status 0 | 19 participants |
| Performance Status 1 | 28 participants |
| Performance Status 2 | 6 participants |
| Prior Taxane Therapy No | 0 participants |
| Prior Taxane Therapy Yes | 53 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 53 |
| serious Total, serious adverse events | 9 / 53 |
Outcome results
Confirmed Prostate-Specific Antigen (PSA) Response
PSA response is defined as a 50% reduction in accordance with the recommendations of the orginal PSA Working Group. Confirmed PSA response is defined as PSA response at two or more time points at least 4 weeks apart, without objective disease progression or symptomatic deterioration.
Time frame: Assessed every 3 cycles (1 cycle = 14 days) until progression
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CNTO 328 | Confirmed Prostate-Specific Antigen (PSA) Response | 3.8 percentage of participants |
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time frame: Patients were assessed for adverse events after every cycle (1 cycle = 14 days) of protocol treatment
Population: Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | AST, SGOT | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Alkaline phosphatase | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | CNS cerebrovascular ischemia | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | DIC (disseminated intravascular coagulation) | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Esophagitis | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Gastritis (including bile reflux gastritis) | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neuropathy: motor | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Pain - Muscle | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Pain-Other (Specify: hip and back) | 1 Participants |
| CNTO 328 | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Platelets | 2 Participants |
Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease
Complete Response (CR) is a complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. PSA = .2 ng/ml. Partial Response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.
Time frame: Assessed every 3 cycles (1 cycle= 14 days) of treatment until progression
Population: All eligible patients with measurable disease who started treatment were included in the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CNTO 328 | Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | Complete Repsonse (CR) | 0 participants |
| CNTO 328 | Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | Partial Response (PR) | 0 participants |
| CNTO 328 | Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | Unconfirmed Complete Response | 0 participants |
| CNTO 328 | Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | Unconfirmed Partial Response | 0 participants |
| CNTO 328 | Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | Stable Disease | 7 participants |
| CNTO 328 | Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable Disease | No response | 24 participants |
Overall Survival (OS)
Measured from date of registration to date of death due to any cause or last contact
Time frame: 0-3 yeas after registration
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CNTO 328 | Overall Survival (OS) | 11.6 months |
Progression-free Survival (PFS)
PFS is defined as tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, PSA progression by PSA Working Group criteria, or symptomatic deterioration.
Time frame: Assessed every 3 cycles (1 cycle = 14 days) until progression
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CNTO 328 | Progression-free Survival (PFS) | 1.6 months |