Prostate Cancer, Prostatic Neoplasms
Conditions
Keywords
Castration-resistant prostate cancer, Prostate Cancer, JEVTANA, Cabazitaxel, Bavituximab
Brief summary
This is a Phase Ib/IIa Study of Cabazitaxel plus Bavituximab in patients with castration-resistant prostate cancer (CRPC). The current study is designed to determine if the addition of bavituximab to cabazitaxel will improve progression free survival (PFS) or overall survival (OS). In addition, the Lead Researcher is requiring the collection of urine, and blood specimens for future research. This study will enroll patients with CRPC, who have been previously treated with docetaxel or a docetaxel-containing regimen. Patients may be intolerant of, or resistant to, docetaxel, or may have been previously treated with the agent without definite disease progression during therapy. Patients must meet the study eligibility criteria and must be competent to give informed consent.
Detailed description
Cabazitaxel will be administered IV on day 1 of each 21-day treatment cycle. Bavituximab (3 mg/kg) will be administered as an intravenous (IV) infusion on a weekly basis (Cycle 1 Day 2, all other cycles Day 1; day 8, day 15). Patients will receive cabazitaxel (day 1) plus bavituximab weekly of each 21-day cycle for up to 8 cycles. Up to 31 patients will be enrolled to ensure 28 evaluable subjects. The accrual period is expected to be between 12 to 18 months (1-1.5 years). Subjects will remain on the treatment phase of the study until any of the following events occur: * Disease progression as evidenced by an increase in the prostate-specific antigen (PSA) level, worsening of pain, or disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) * Completion of 8 cycles of cabazitaxel-bavituximab therapy (day 169) * Development of toxicity that, in the investigator's judgment, precludes further study participation * Significant protocol violations or noncompliance on the part of the patient or investigator * The investigator's judgment that discontinuation is in the patient's best interest * Initiation of alternative antineoplastic treatments. * Refusal of the patient to continue treatment or follow-up * Loss to follow-up After completion of the treatment phase, subjects will remain on the followup phase of the study until any of the following events occur: * Refusal of the patient to continue treatment or follow-up * Loss to follow-up * Death * The investigator's judgment that discontinuation is in the patient's best interest
Interventions
DRUGCabazitaxel plus bavituximab
Cabazitaxel (25 mg/m2) will be administered IV on Day 1 of each 21-day treatment cycle, and bavituximab (3 mg/kg) will be administered as an IV infusion on a weekly basis (Cycle 1 Day 2, all other cycles Day 1; day 8; day 15) for 8 cycles.
Sponsors
Peregrine Pharmaceuticals
Medical University of South Carolina
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
* Written informed consent has been obtained. * Adults 18 years of age or older with a life expectancy of at least 3 months. * Histologically confirmed castration-resistant prostate cancer (CRPC). Patient must have demonstrated a rising PSA level above the androgen-deprivation therapy (ADT) nadir, on at least two determinations four weeks or more apart. ADT is defined as treatment with a Luteinizing-hormone-releasing hormone (LHRH) agonist or orchiectomy. * Treatment with only one prior chemotherapy regimen, which must contain docetaxel as a single agent or in combination with other agents. Patients may be intolerant of, or resistant to, the cytotoxic drug combination. * Patients on ADT must be willing to continue ADT for the duration of their participation in this protocol. ADT cannot be initiated, and ADT dose/agents may not be changed during the study. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Adequate hematologic function (absolute neutrophil count \[ANC\] ≥ 1,500 cells/μL; hemoglobin ≥ 8 g/dL, platelets ≥ 100,000/μL). * Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min). * Adequate hepatic function (bilirubin ≤ 1.0 x upper limit of normal \[ULN\], alanine aminotransferase \[ALT\] ≤ 1.5 x ULN, aspartate aminotransferase \[AST\] ≤ 1.5 x ULN). * Prothrombin time (PT) / international normalized ratio (INR) ≤ 1.5 × ULN. * Activated partial thromboplastin (aPTT) time ≤ 1.5 × ULN. * Prostate-specific antigen (PSA) level of at least 2 ng/mL. * New York Heart Association classification I or II. * All patients of reproductive potential must agree to use an approved form of contraception (as determined by the investigator).
Exclusion criteria
* Known history of bleeding diathesis or coagulopathy (e.g., von Willebrand disease or hemophilia). * Any history of thromboembolic events (e.g., deep vein thrombosis or pulmonary thromboembolism); central venous catheter-related thrombosis \> 6 months before Screening is allowed. * Ongoing therapy with oral or parenteral anticoagulants; patients on low-dose anticoagulants to maintain patency of central venous catheters are eligible. * Grade 2 or higher peripheral neuropathy (e.g., numbness, tingling, and/or pain in distal extremities). * Radiotherapy (teletherapy or brachytherapy) , chemotherapy or estrogen agonist within 28 days before Study Day 1. * Systemic radiotherapy (Sm-153, Sr-89) within 56 days before study day 1. * Symptomatic or clinically active brain metastases. * Major surgery within 28 days of Study Day 1. * Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease). * Any history of cerebrovascular accident, or transient ischemic attack at any time, or history of symptomatic coronary artery disease \< 6 months before screening. * A history of any condition requiring anti-platelet therapy (eg, phosphodiesterase inhibitors, adenosine diphosphate receptor antagonists), with the exception of general cardiovascular prophylaxis with aspirin (≤ 325 mg/day). * Serious non-healing wound (including wound healing by secondary intention, ulcer, or bone fracture). * Known chronic infection with human immunodeficiency virus (HIV) or viral hepatitis. * Contraindication to intravenous (IV) contrast media.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Progression-free Survival at Day 85 | 12 weeks | The primary objective of this study is to determine the probability of progression-free survival (PFS) after 12 weeks of therapy in subjects with CRPC treated with cabazitaxel + bavituximab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of PSA Response Rate | 24 weeks | To estimate the PSA response rate from cabazitaxel + bavituximab therapy in CRPC patients previously treated with docetaxel. PSA response rate will be assessed at multiple time points during the 24 wks of study treatment. |
| Objective Response Rate by RECIST for Patients With Measurable Disease | 24 weeks | To estimate the objective response rate from cabazitaxel + bavituximab therapy in CRPC patients previously treated with docetaxel. Objective response rate will be assessed at day 85, 169 |
| Overall Survival | 24+ weeks | To estimate the overall survival in subjects with CRPC (previously treated with docetaxel) following cabazitaxel + bavituximab therapy. Overall survival will be assessed continually during the duration of the study. |
| Number of With Grade 3 or 4 Toxicities | 24 weeks | To document the toxicity of cabazitaxel + bavituximab therapy in CRPC patients previously treated with docetaxel. Toxicity will be assessed continually during the 24 wks of study therapy. |
| Progression-free Survival (PFS) | 24+ weeks | Determination of progression-free survival in subjects treated with cabazitaxel + bavituximab for CRPC previously treated with docetaxel. PFS will be assessed continually during the entire study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cabazitaxel Plus Bavituximab Cabazitaxel (25 mg/m2) will be administered IV on Day 1 of each 21-day treatment cycle. Bavituximab (3 mg/kg) will be administered as an IV infusion on a weekly basis (Cycle 1 Day 2, all other cycles Day 1; day 8; day 15) for 8 cycles.
Cabazitaxel plus bavituximab: Cabazitaxel (25 mg/m2) will be administered IV on Day 1 of each 21-day treatment cycle, and bavituximab (3 mg/kg) will be administered as an IV infusion on a weekly basis (Cycle 1 Day 2, all other cycles Day 1; day 8; day 15) for 8 cycles. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Cabazitaxel Plus Bavituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 4 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Probability of Progression-free Survival at Day 85
The primary objective of this study is to determine the probability of progression-free survival (PFS) after 12 weeks of therapy in subjects with CRPC treated with cabazitaxel + bavituximab.
Time frame: 12 weeks
Population: This study terminated early, so outcomes were not analyzed.
Secondary
Measurement of PSA Response Rate
To estimate the PSA response rate from cabazitaxel + bavituximab therapy in CRPC patients previously treated with docetaxel. PSA response rate will be assessed at multiple time points during the 24 wks of study treatment.
Time frame: 24 weeks
Population: This study terminated early, so outcomes were not analyzed.
Secondary
Number of With Grade 3 or 4 Toxicities
To document the toxicity of cabazitaxel + bavituximab therapy in CRPC patients previously treated with docetaxel. Toxicity will be assessed continually during the 24 wks of study therapy.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabazitaxel Plus Bavituximab | Number of With Grade 3 or 4 Toxicities | 5 grade 3 or 4 toxicities |
Secondary
Objective Response Rate by RECIST for Patients With Measurable Disease
To estimate the objective response rate from cabazitaxel + bavituximab therapy in CRPC patients previously treated with docetaxel. Objective response rate will be assessed at day 85, 169
Time frame: 24 weeks
Population: This study terminated early, so outcomes were not analyzed.
Secondary
Overall Survival
To estimate the overall survival in subjects with CRPC (previously treated with docetaxel) following cabazitaxel + bavituximab therapy. Overall survival will be assessed continually during the duration of the study.
Time frame: 24+ weeks
Population: This study terminated early, so outcomes were not analyzed.
Secondary
Progression-free Survival (PFS)
Determination of progression-free survival in subjects treated with cabazitaxel + bavituximab for CRPC previously treated with docetaxel. PFS will be assessed continually during the entire study.
Time frame: 24+ weeks
Population: This study terminated early, so outcomes were not analyzed.