Metastatic castrate-resistant prostate cancer MedDRA version: 13.1 Level: LLT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 13.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: eIF-4E Antisense Oligonucleotide
Product Code: ISIS 183750
Pharmaceutical Form: Solution for injection
Current Sponsor code: ISIS 183750
Other descriptive name: LY2275796
Concentration u
Sponsors
Isis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Patients with castrate-resistant prostate cancer are eligible to be included in the study only if they meet all of the following criteria: 1. Provide written informed consent prior to Screening. 2. Age = 18 years. 3. Histological or cytological diagnosis of adenocarcinoma of the prostate. 4. Metastatic disease for which no curative therapy exists and for which systemic chemotherapy is indicated. 5. Progression of disease despite either medical or surgical castration. If the patient received medical androgen ablation, a castrate level of testosterone (= 50 ng/dL) must have been present concurrent with disease progression. Progressive disease is defined as any one of the following: • Rising serum PSA levels: two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart with the value of the third point being = 2 ng/mL. If the third PSA level is less than the second, an additional fourth test to confirm a rising PSA (i.e., the fourth value is = the second value and is = 2 ng/mL) is acceptable. • Progressive measurable disease defined as an increase in the sum of the diameters of measurable lesions over the smallest sum observed or the appearance of one or more new lesions as assessed by CT scan. • Bone progressions: appearance of 2 or more new lesions on bone scan or other imaging. 6. If patient did not have a surgical orchiectomy: • The patient must be on androgen suppression treatment (e.g. LHRH agonist), have a castrate level of testosterone (= 50 ng/dL), and must be willing to continue the treatment throughout the study. • The patient must have discontinued treatment with anti-androgens (discontinued = 4 weeks for flutamide and = 6 weeks for nilutamide or bicalutamide prior to Screening) and have documented disease progression following discontinuation. 7. PSA = 2 ng/mL during the Screening period. 8. Performance status of 0 or 1 on the ECOG Performance Status Scale. 9. Have an estimated life expectancy of at least 12 weeks. 10. Adequate organ function within 14 days prior to first study dose (ISIS 183750 or docetaxel, whichever occurs first) including the following: a. Absolute neutrophil count (ANC) = 1.5 x 10(9)/L. b. Platelet count = 100 x 10(9)/L. c. Total bilirubin = 1.0 x upper limit of normal (ULN). d. Aspartate aminotransferase (AST) = 1.5 x ULN. e. Alanine aminotransferase (ALT) = 1.5 x ULN. f. Serum creatinine = 1.5 x ULN. g. Prothrombin time (PT) and international normalized ratio (INR) within normal limits. h. Activated partial thromboplastin time (aPTT) within normal limits. 11. Part 1: Have had no more than 1 prior chemotherapy or biological therapy regimen (approved or experimental; all previous hormonal therapies are allowed and not counted as biological therapy for this inclusion criterion) for prostate cancer. This does not include treatments that may have been received in the adjuvant or neoadjuvant setting. A regimen is defined as two or more consecutive cycles of treatment. Part 2: Have had no prior chemotherapy or biological therapy (approved or experimental; all previous hormonal therapies are allowed and not counted as biological therapy for this inclusion criterion) in any setting for prostate cancer. 12. Have discontinued all previous therapies for cancer (except treatment with LHRH analogues) as follows: a. Part 1: cytotoxic chemotherapy must be discontinued at least 4 weeks prior to screening; Part 2: see Inclusion Criteria 11. b. Part 1: biological tre
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria: 1. Treatment with another investigational drug or device within 4 weeks or biological agent within 6 weeks before Screening or 5 half-lives of study agent, whichever is longer. 2. Pre-existing peripheral neuropathy = Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE) Grade 2. 3. Patients with treated or untreated parenchymal brain metastases or leptomeningeal disease. Currently active malignant epidural disease is also excluded. Previously treated epidural disease does not exclude the patient from the study. (Note: CT or MRI of brain is not needed to rule these out unless the patient has clinical symptoms suggestive of CNS metastases). 4. Have active infection or serious concomitant systemic disorder (for example, heart failure) incompatible with the study (at the discretion of the Investigator). 5. Presence or history of other malignancies except non-melanoma skin cancer or solid tumors curatively treated at least 5 years previously with no subsequent evidence of recurrence. 6. Presence of an underlying disease state associated with active bleeding. 7. Ongoing therapy with oral or parenteral anticoagulants (e.g., heparin, warfarin/coumadin). Low-dose anticoagulants for maintenance of catheter patency and low dose aspirin (= 325 mg/day) and nonsteroidal antiinflammatory agents are not exclusionary. 8. Concurrent treatment with other anticancer drugs. 9. Inability to comply with protocol or study procedures. 10. Previous therapy with strontium or samarium. 11. Patients who have had irradiation of = 25% of the bone marrow (e.g. pelvic irradiation). 12. Use of any herbal products, including saw palmetto within 1 week of screening and throughout the study. 13. Initiation of treatment with bisphosphonates, or change in dose, within 4 weeks of assignment to dosing in this study. Patients taking bisphosphonates should not have their dosing regimen altered during the study unless medically warranted. 14. Known history of HIV, HCV, or chronic HBV infection. 15. Previous treatment with a therapeutic antisense oligonucleotide or siRNA. 16. Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. 17. Have any other medical conditions that, in the opinion of the Investigator, would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In Part 1, the primary objective is to examine the safety and tolerability of ISIS 183750 in combination with docetaxel and prednisone in order to determine the ISIS 183750 dose for evaluation in Part 2. In Part 2, the primary objective is to estimate the progression-free survival in patients treated with ISIS 183750 in combination with docetaxel and prednisone.;Secondary Objective: Part 1: • To characterize the plasma and urine PK parameters of ISIS 183750 in the absence and presence of docetaxel • To characterize the plasma PK parameters for docetaxel in the presence of ISIS 183750 • To explore anticancer effects of ISIS 183750 in combination with docetaxel and prednisone Part 2: • To estimate overall survival • To estimate the effect of treatment on PSA parameters including: - Percent change from baseline to the end of the 4th treatment cycle - Maximum post-baseline percent reduction - Time to PSA progression • To examine tumor response by RECIST version 1.1 including: - Percent change of tumor size from baseline to the end of the 4th treatment cycle - Objective tumor response rate - Duration of objective tumor response for responding patients - Time to tumor progression • To determine the 7-day plasma trough levels of ISIS 183750 • To determine the safety and tolerability of ISIS 183750 in combination with docetaxel and prednisone;Primary end point(s): The primary efficacy endpoint is the progression-free survival, with progression defined as: • PSA progression according to PCWG2 criteria (including the recommendation that rising PSA alone as the basis for progression should be avoided), • Tumor progression in lung, liver, lymph nodes and other soft tissue, by modified RECIST 1.1 criteria, • Bone progression defined as two or more new lesions on bone scan, • Worsening symptoms and/or • Death | — |
Countries
Hungary
Outcome results
None listed