Trial Information

A Phase I Study of a Chimeric Antibody Against Interleukin-6 (CNTO 328) Combined With Docetaxel in Subjects With Metastatic Hormone-Refractory Prostate Cancer

This is a Phase 1 open-label, multicenter, nonrandomized study of the safety and
pharmacokinetics of the combination of CNTO 328 and docetaxel in patients with metastatic
Hormone-Refractory Prostate Cancer (HRPC). Eligible patients must be age >= 18 years, have
histologically or cytologically confirmed adenocarcinoma of the prostate, and have
documented metastatic disease. Prior chemotherapy for metastatic disease is not allowed.The
study will last for approximately 26 months. This study will be conducted in 4 phases: 1.
Screening (up to 4 weeks): understanding and signing an informed consent form,
physical/neurological exam, an ECG, vitals will be checked, urinalysis, a radiologic
assessment, routine blood samples, study blood samples, a circulating tumor cell blood
sample, a testosterone level blood sample, and a prostate specific antigen (PSA) sample. If
the results show that the patient can be a part of the study, the patient will begin the
run-in phase. If the results of the screening show that the patient cannot be part of the
study, the patient will not receive docetaxel as part of this study or CNTO 328.Starting
with the first docetaxel infusion, the patient will be required to take prednisone twice a
day, until the end of Cycle 3. After Cycle 3, the study doctor will decide if and/or when
the prednisone taken. Dexamethasone will be required at 12 hours, 3 hours, and 1 hour
before the start of every docetaxel infusion through Cycle 3. After Cycle 3, the study
doctor will decide how the dexamethasone will be taken. Antiemetics (to prevent nausea and
vomiting) are also required. The study doctor will decide the dose, how often, and how
these should take them 2. Run-in Phase (up to 3 weeks):The term run-in phase describes a
period of time before the start of the formal study treatment. During this phase, the
patient will receive only one drug, either docetaxel or CNTO 328 depending on the assigned
group. Groups 1A, 2, and 3: The patient will be given docetaxel 3 weeks before the formal
study treatment begins. During the next 2 weeks the patient will not receive any study
drug, but will undergo certain tests and procedures. Group 1B: The patient will be given a
CNTO 328 infusion 2 weeks before the formal study treatment begins. During the next week
the patient will not receive any study drug, but will have certain tests and procedures. 3.
Cycles 1 through 17 (14 cycles - up to 46 weeks and with additional 3 cycles -up to 55
weeks):Cycles 1 through 17 are each planned to be 3 weeks in length. All treatment groups
will receive an infusion of docetaxel on week 1 of every cycle. The CNTO 328 infusion
occurs based on the treatment group to which the patients are assigned. Group 1A: Patients
will receive a 6mg/kg infusion of CNTO 328 every two weeks, starting on week 1, cycle 1.
Group 1B: Patients will receive a 6mg/kg infusion of CNTO 328 every two weeks, starting two
weeks prior to cycle 1.Group 2: Patients will receive a 9 mg/kg infusion of CNTO 328 every
three weeks, starting on week 1, cycle 1. Group 3: Patients will receive a 12mg/kg
infusion of CNTO 328 every three weeks, starting on week 1, cycle 1. The overall amount of
CNTO 328 increases with each higher group. Therefore, Group 1A and 1B will be filled before
Group 2, and Group 2 will be filled before Group 3. This allows CNTO 328 to be tested in a
safer manner. The docetaxel dose remains the same for all three groups.Patients may receive
up to 14 cycles of treatment provided there is no evidence of disease progression, including
serum PSA progression, or unacceptable toxicity. However, patients responding to treatment
with at least stable disease (SD) after 14 cycles will be permitted to receive 3 additional
cycles of treatment. In addition to drug therapy, patients will receive other tests and
procedures. Most of the tests required before study medication is administered and
throughout the study would be done normally during any treatment for prostate cancer.
However, these tests and procedures may be done more often. The following are the tests and
procedures: Routine blood tests; Study blood samples; Testosterone level sample; PSA sample;
Circulating Tumor Cell blood sample; Urinalysis; Physical exam/neurological exam; Vital
signs; ECG (electrocardiogram); Radiological tests4. Follow-up: After patients complete
treatment they will have follow-up visits including patients that discontinue treatment
early. The patients will have them 1, 2, 3, and 4 weeks after the final treatment cycle is
completed. The Week 4 visit will be the "End of Study Visit". There will be 3 more visits
at 12, 18, and 24 weeks after the final treatment cycle. Long-term Follow-up: No matter
when or why the patients leave the study, the study doctor or nurse may telephone them to
ask about their health and/or look at their medical records every 3 months to check on how
they are doing. They will do this for one year after the last infusion of study drug.
Patients will not need to go to the study center or have any tests performed. The study
center will also ask about any treatment the patient received after they completed their
participation in the study . Docetaxel 75 mg/m2 will be given intravenously (into the
vein) once every 3 wks for up to 17 three week cycles. CNTO328 will be administered
intravenously (into the vein) over 2 hours according to one of the following regimens: 6
milligrams of medication per kilogram of body weight (mg/kg) once every 2 wks; 9 mg/kg once
every 3 wks; and 12 mg/kg every 3 wks for up to 17 three week cycles.