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S0354, Anti-IL-6 Chimeric Monoclonal Antibody in Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy

A Phase II Study of CNTO 328, A Monoclonal Antibody Against Interleukin-6 (IL-6), in Patients With Hormone Refractory Prostate Cancer

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00433446
Enrollment
62
Registered
2007-02-12
Start date
2007-04-30
Completion date
2011-07-31
Last updated
2013-02-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

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

BIOLOGICALCNTO 328

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
SWOG Cancer Research Network
Lead SponsorNETWORK

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

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

MeasureTime frameDescription
Confirmed Prostate-Specific Antigen (PSA) ResponseAssessed every 3 cycles (1 cycle = 14 days) until progressionPSA 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

MeasureTime frameDescription
Progression-free Survival (PFS)Assessed every 3 cycles (1 cycle = 14 days) until progressionPFS 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 registrationMeasured 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 DiseaseAssessed every 3 cycles (1 cycle= 14 days) of treatment until progressionComplete 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 DrugPatients were assessed for adverse events after every cycle (1 cycle = 14 days) of protocol treatmentAdverse 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

ArmCount
CNTO 328
CNTO 328 will be given 6 mg/kg through intravenous (IV) once per cycle ( 1 cycle= 14 days) for 12 cycles
53
Total53

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event4
Overall StudyIneligible9
Overall StudyOther - Not Protocol specified3
Overall StudyProgression44
Overall StudyRefusal Unrelated to Adverse Event1

Baseline characteristics

CharacteristicCNTO 328
Age Continuous71 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 typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
47 / 53
serious
Total, serious adverse events
9 / 53

Outcome results

Primary

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

ArmMeasureValue (NUMBER)
CNTO 328Confirmed Prostate-Specific Antigen (PSA) Response3.8 percentage of participants
Secondary

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.

ArmMeasureGroupValue (NUMBER)
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugAST, SGOT1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugAlkaline phosphatase1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugCNS cerebrovascular ischemia1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugDIC (disseminated intravascular coagulation)1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugEsophagitis1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugGastritis (including bile reflux gastritis)1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugLeukocytes (total WBC)1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugNeuropathy: motor1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugNeutrophils/granulocytes (ANC/AGC)1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugPain - Muscle1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugPain-Other (Specify: hip and back)1 Participants
CNTO 328Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study DrugPlatelets2 Participants
Secondary

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

ArmMeasureGroupValue (NUMBER)
CNTO 328Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable DiseaseComplete Repsonse (CR)0 participants
CNTO 328Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable DiseasePartial Response (PR)0 participants
CNTO 328Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable DiseaseUnconfirmed Complete Response0 participants
CNTO 328Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable DiseaseUnconfirmed Partial Response0 participants
CNTO 328Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable DiseaseStable Disease7 participants
CNTO 328Objective Response (Confirmed and Unconfirmed Complete and Partial Response) Among Those Patients With Measurable DiseaseNo response24 participants
Secondary

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

ArmMeasureValue (MEDIAN)
CNTO 328Overall Survival (OS)11.6 months
Secondary

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

ArmMeasureValue (MEDIAN)
CNTO 328Progression-free Survival (PFS)1.6 months

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026