Evaluate the efficacy and safety of treatment with CNTO 95 in combination with docetaxel and prednisone compared with docetaxel and prednisone without CNTO 95 in subjects with metastatic HRPC.
ID
Source
Brief title
Condition
- Reproductive and genitourinary neoplasms gender unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is progression-free survival (PFS), defined as the time from
the date of randomization until the first documented sign of disease
progression (radiographic, clinical, or both) or death due to any cause,
whichever occurs sooner.
Secondary outcome
• Tumor response rate
• PSA response rate
• Overall survival
• Change from baseline in ECOG performance status
Background summary
CNTO 95 is an antibody made by Centocor. Antibodies are substances in the body
that fight infection. CNTO 95 works by blocking substances on cells called
integrins that are involved in formation of new blood vessels (angiogenesis).
More specifically, cancer drugs like CNTO 95, work by preventing the formation
of blood vessels that feed tumors. These types of cancer drugs are called
anti-angiogenic drugs. When new blood vessels are stopped from being made,
tumors cannot get the food and oxygen they need to grow. As a result
anti-angiogenic drugs may stop tumors from growing and spreading.
In laboratory studies, CNTO 95 appeared to slow tumor growth without
significant side effects. However, laboratory studies do not always predict how
the drug will work in humans. Before this study, CNTO 95 was given to over 50
people with different types of advanced cancer that did not respond to standard
treatment. The reported side effects are described in the Risks section.
In this study the combination of CNTO 95 with docetaxel and prednisone will be
tested to see if it is safe and to see what effects it has on your cancer.
Docetaxel and prednisone are approved chemotherapy (cancer drug) for HRPC. In
previous studies at least 6 patients received CNTO 95 in combination with
docetaxel and prednisone. It is too early to know if CNTO 95 works, either
alone or in combination with docetaxel and prednisone.
Study objective
Evaluate the efficacy and safety of treatment with CNTO 95 in combination with
docetaxel and prednisone compared with docetaxel and prednisone without CNTO 95
in subjects with metastatic HRPC.
Study design
Randomized, Double-blind, Multicenter, Phase 2 Study of a Human Monoclonal
Antibody to Human αv Integrins (CNTO 95) in Combination With Docetaxel and
Prednisone for the First-Line Treatment of Subjects With Metastatic Hormone
Refractory Prostate Cancer.
Intervention
Not Applicable.
Study burden and risks
Safety information is available for over 50 subjects who received doses up to
10 mg/kg CNTO 95. The side effects most frequently observed were fever,
chills, drowsiness, and headache. Less frequently reported side effects were
abdominal pain, constipation, liver enzyme increases, low blood salt levels,
pain, nausea, loss of appetite, vomiting, coughing and diarrhea.
Subjects receiving CNTO 95 had mild to moderate headaches, chills, fever or a
combination on the day of infusion. These all improved within a few hours.
Risk of CNTO 95 and docetaxel given in combination:
So far at least 6 patients have been treated with the above mentioned
combination. No increase of the side effects of either CNTO 95 or docetaxel has
been observed. These data however are too limited to know if these drugs will
affect each other or affect the potential side effects of either drug listed
above.
Roderveldlaan 1
2600 Berchem
BE
Roderveldlaan 1
2600 Berchem
BE
Listed location countries
Age
Inclusion criteria
1. Are male >= 18 years of age.
2. Have histologically or cytologically confirmed adenocarcinoma of the prostate.
3. Have radiologic or clinical evidence of metastatic disease.
4. Have progressive hormone-refractory disease after orchiectomy or gonadotropinreleasing
hormone analog and/or antiandrogen treatment within 6 months prior to
the first study agent administration, documented by at least 1 of the following:
a. Transaxial imaging (CT or MRI) tumor progression
b. Rise in 2 consecutive PSA values obtained at least 14 days apart
c. Radionucleotide bone scan with at least 2 new lesions
5. Have an ECOG score <= 2.
6. Have adequate bone marrow, liver, and renal function, defined as follows:
a. Absolute neutrophil count (ANC) >= 1.5 × 109/L
b. Hemoglobin >= 10 g/dL (without transfusion)
c. Platelets >= 100 × 109/L
d. AST and ALT < 2.5 × ULN
e. Alkaline phosphatase < 5 × ULN
f. Total bilirubin within normal limits
g. Creatinine <= 1.5 mg/dL
h. Activated partial thromboplastin time (aPTT) and prothrombin time (PT)
<= 1.5 × ULN
7. Have testosterone < 50 ng/mL for subjects without surgical castration.
Testosterone level will not be documented for subjects who have been surgically
castrated.
8. Have serum PSA >= 5.0 ng/mL.
9. Have a life expectancy > 12 weeks.
10. Have at least 4 weeks from previous major surgery to date of first study agent
administration. Subjects must have recovered or stabilized from previous surgery.
11. Have discontinued flutamide > 4 weeks prior to the first study agent
administration, or have discontinued nilutamide or bicalutamide > 6 weeks prior
to the first study agent administration.
12. Use appropriate contraception (eg, condom) for the duration of the study and for 3 months after the last study treatment.
13. Provide signed and dated informed consent(s) prior to any study-specific
procedures and agree to comply with all protocol-specified procedures.
Exclusion criteria
1. Have known CNS metastases.
2. Had prior systemic nonhormonal therapy for HRPC.
3. Received any investigational drug/agent within 30 days or 5 half-lives, whichever
is longer.
4. Had a prior malignancy (other than prostate cancer) except for adequately treated
superficial bladder cancer, basal cell or squamous cell carcinoma of the skin, or
other cancer for which the subject has been disease-free for >= 5 years.
5. Have known HIV seropositivity or known hepatitis B or C infection.
6. Have planned major surgery during the study.
7. Had prior radiotherapy to > 25% of the marrow-containing skeleton.
8. Have peripheral neuropathy > Grade 1.
9. Have a history of uveitis.
10. Have taken any over-the-counter or herbal treatment for prostate cancer within
4 weeks prior to the first study agent administration.
11. Have a serious concurrent illness or significant cardiac disease characterized by
significant ischemic coronary disease, significant arrhythmias (requiring active
treatment), or congestive heart failure New York Heart Association (>= NYHA II)
or myocardial infarction within the previous 6 months.
12. Have any uncontrolled medical condition, serious infection, or the presence of
clinically significant laboratory abnormalities that places the subject at
unacceptable risk by participating in the study or confounds the ability to interpret
data from the study.
13. Requires hematopoietic growth factors or transfusion of blood products to meet
eligibility criteria.
14. Had prior use of radionucleotide therapy (eg, Strontium89, Samarium).
15. Undergoing concurrent immunotherapy, biotherapy, radiotherapy, investigational
therapy, or steroid therapy other than that included in this protocol (except for
topical or inhaled steroids, or unless clinically indicated [eg, for reactions to IV
contrast, allergic reactions that develop during the study, severe nausea,
vomiting]).
16. Requires concurrent anticoagulation therapy (except for low-dose prophylaxis).
17. Have known hypersensitivity to docetaxel or its components.
18. Have a history of anaphylaxis or severe allergic reaction(s) to human Ig therapy
or polysorbate 80 (formulation components of CNTO 95).
19. Has history of bleeding diathesis.
20. Had recurrent arterial or venous thromboembolism within 6 months preceding
enrollment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-005766-39-NL |
| CCMO | NL17045.091.07 |