A Phase 1b/2 Study of Docetaxel and Prednisone, with or without ISIS 183750 (an eIF4E Inhibitor), inPatients with Castrate-Resistant Prostate Cancer - N/A

• Conditions: Metastatic castrate-resistant prostate cancer; MedDRA version: 13.1Level: LLTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 13.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2010-022239-12-HU
• Lead Sponsor: Isis Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-31
• Last Update Posted: 2 December 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 112

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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified