This phase I/II trial studies the side effects and best dose of pasireotide and to see how well it works when given together with docetaxel and prednisone in treating patients with metastatic hormone-resistant prostate cancer. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pasireotide may inhibit the secretion of hormones. Giving pasireotide together with docetaxel and prednisone may kill more tumor cells.
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) level of SOM 230 (pasireotide) in combination with docetaxel and prednisone. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination in metastatic castration-resistant prostate cancer (CRPC). II. To evaluate preliminary efficacy of the combination of SOM 230 and docetaxel and prednisone as defined by response rates (measurable and prostate-specific antigen \[PSA\]), time to progression (TTP) and overall survival (OS). III. To evaluate the pharmacokinetics (PK) of the combination. IV. To assess the pharmacodynamic (PD) effects of the combination as seen by baseline levels of and changes in insulin-like growth factor (IGF)-1, serum chromogranin A (SCA), and neuron specific enolase (NSE), and to associate them with TTP and OS. V. To assess the pretherapy circulating tumor cell (CTC) counts and change in CTC after therapy, and to associate them with TTP and OS. OUTLINE: This is a phase I dose-escalation study of pasireotide followed by a phase II study. Patients receive pasireotide intramuscularly (IM) on day 1, docetaxel intravenously (IV) over 1 hour, and prednisone orally (PO) twice daily (BID) continuously. Courses with docetaxel repeat every 21 days and courses with pasireotide repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 28 days and then every 3 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
To identify the maximum tolerated dose (MTD) of pasireotide, The occurrence rate of binary endpoints (eg, specific types of toxicity at a certain dose level and severity grade, response, etc) will be described by point estimates and exact 90% confidence intervals (CIs) for proportions using Wilson's method.
Time frame: Up to day 57
The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0
The count of patients who experience a given type and grade of toxicity as assessed via NCI CTCAE version 4.0
Time frame: On days 1, 8, 15, 22, 29, 36 43, 50 and 57
Measurements of Tumor Using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria Before and After Treatment With the Combination of Pasireotide in Combination With Docetaxel
Percentage of participants responding to treatment by measurements of tumor using Response Evaluation Criteria In Solid Tumors (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, before and after treatment with the combination of pasireotide in combination with docetaxel
Time frame: Every 12 weeks for the first 36 weeks and then every 16 weeks thereafter up to 100 weeks
Percentage Prostate-specific Antigen (PSA) Change Noted
Percentage change of prostate-specific antigen (PSA) decline or increase noted
Time frame: On days 1, 22, 43
Time to Progression (TTP)
Time from Treatment start date to Progression (TTP) Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study, up to 2 years
Overall Survival (OS)
Time from Treatment start date to date of death or last follow-up.
Time frame: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study
Pharmacokinetics (PK) of SOM230
Pharmacokinetics (PK) of SOM230 measured in the bloodstream (in ng/ml) at days 29, 57, and 85.
Time frame: Predosing/end of infusion/2, 3, 4 ,7, 24 and 48 hours after start of docetaxel; Day 43; predosing for docetaxel and pasireotide/end of infusion/2, 3, 4, 7, 24 hours day 44/48 hours day 45 after start of infusion; days 29, 57, and 85 prior to pasireotide
Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy
Measurement of levels of IGF-1, serum chromogranin A (SCA), and neuron specific enolase (NSE), the change between time points (day 22 and day 43) from day 1 as measured in percent change.
Time frame: Baseline and days 22 and 43
Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy
Measurements of CTC counts, the change between time-points (day 22 and day 43) from day 1 as measured in percent change.
Time frame: Baseline and days 22 and 43
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