Safety and Tolerability Study of ISIS EIF4E Rx in Combination With Docetaxel and Prednisone (CRPC)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01234025
First received: November 2, 2010
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to examine the safety, tolerability and progression-free survival of patients with Castrate-Resistant Prostate Cancer treated with ISIS EIF4E Rx in combination with docetaxel and prednisone.


Condition Intervention Phase
Castrate-Resistant Prostate Cancer
Drug: ISIS EIF4E Rx
Drug: Prednisone
Drug: Docetaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Docetaxel and Prednisone, With or Without ISIS 183750 (an eIF4E Inhibitor), in Patients With Castrate-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: At the end of each 21 day cycle ] [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: November 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 Cohort 1 Drug: ISIS EIF4E Rx
800 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle.
Drug: Prednisone
5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle
Drug: Docetaxel
75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle
Experimental: Part 1 Cohort 2 Drug: ISIS EIF4E Rx
1000 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle.
Drug: Prednisone
5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle
Drug: Docetaxel
75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle
Experimental: Part 2 Arm A Drug: Prednisone
5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle
Drug: Docetaxel
75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle
Experimental: Part 2 Arm B Drug: ISIS EIF4E Rx
(Dose identified in Part 1)ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle.
Drug: Prednisone
5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle
Drug: Docetaxel
75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent prior to Screening.
  • Age ≥ 18 years.
  • Histological or cytological diagnosis of adenocarcinoma of the prostate.
  • Metastatic disease for which no curative therapy exists and for which systemic chemotherapy is indicated.
  • Progression of disease despite either medical or surgical castration. If the patient received medical androgen ablation, a castrate level of testosterone (> or = 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.
  • 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 (< or = 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.
  • PSA > or = 2 ng/mL during the Screening period.
  • Performance status of 0 or 1 on the ECOG Performance Status Scale.
  • Have an estimated life expectancy of at least 12 weeks.
  • Adequate organ function within 14 days prior to first study dose (ISIS EIF4E Rx or docetaxel, whichever occurs first) including the following:

    • Absolute neutrophil count (ANC) > or = 1.5 x 109/L.
    • Platelet count > or = 100 x 109/L.
    • Total bilirubin < or = 1.0 x upper limit of normal (ULN).
    • Aspartate aminotransferase (AST) < or = 1.5 x ULN.
    • Alanine aminotransferase (ALT) < or = 1.5 x ULN.
    • Serum creatinine < or = 1.5 x ULN.
    • Prothrombin time (PT) and international normalized ratio (INR) within normal limits.
    • Activated partial thromboplastin time (aPTT) within normal limits.
  • 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.
  • Have discontinued all previous therapies for cancer (except treatment with LHRH analogues) as follows:

    • Part 1: cytotoxic chemotherapy must be discontinued at least 4 weeks prior to screening; Part 2: see Inclusion Criteria 11.
    • Part 1: biological treatment (other than hormonal treatments) must be discontinued for at least 6 weeks prior to screening; Part 2: see Inclusion Criteria 11.
    • Hormone therapies (e.g., abiraterone, MDV3100) must have been discontinued 4 weeks prior to screening.
    • Radiotherapy must be discontinued at least 4 weeks prior to screening, and the patient must have recovered from the acute effects of therapy.
  • Recovery from all toxicities of prior therapy to ≤ Grade 2 by NCI CTCAE, version 4.0 (Exception: any toxicity that in the view of the Investigator is not a clinically significant safety risk for further therapy administration, including, but not limited to: anemia, fatigue, erectile dysfunction, hot flashes, lymphedema of an extremity, dizziness, cough, and urinary incontinence).
  • Men of reproductive potential must agree to use an effective form of contraception, as determined by the Investigator, during the treatment period of the study and for 10 weeks following the last dose of study drug.
  • The patient is willing and able to comply with the study visit schedule and procedures, and geographic proximity (Investigator's discretion) that allows adequate follow-up.

Exclusion Criteria:

  • 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.
  • Pre-existing peripheral neuropathy > or = Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE) Grade 2.
  • 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).
  • Have active infection or serious concomitant systemic disorder (for example, heart failure) incompatible with the study (at the discretion of the Investigator).
  • 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.
  • Presence of an underlying disease state associated with active bleeding.
  • 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.
  • Concurrent treatment with other anticancer drugs.
  • Inability to comply with protocol or study procedures.
  • Previous therapy with strontium or samarium.
  • Patients who have had irradiation of ≥ 25% of the bone marrow (e.g. pelvic irradiation).
  • Use of any herbal products, including saw palmetto within 1 week of screening and throughout the study.
  • 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.
  • Known history of HIV, HCV, or chronic HBV infection.
  • Previous treatment with a therapeutic antisense oligonucleotide or siRNA.
  • Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234025

  Hide Study Locations
Locations
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
United States, California
San Bernardino Urological Associates
San Bernardino, California, United States, 92404-4816
United States, Connecticut
Norwalk Hospital- Whittingham Cancer Center
Norwalk, Connecticut, United States, 06850
United States, Florida
Lakeland Regional Cancer Center
Lakeland, Florida, United States, 33805
University of Miami, Miller School of Medicine - Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Louisiana
Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center
Shreveport, Louisiana, United States, 71103
United States, New York
St. Luke's - Roosevelt Hospital Center
New York, New York, United States, 10019
James P. Wilmont Cancer Center - University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Hungary
National Institute of Oncology
Budapest, Hungary, 1122
Szent Janos Hospital and Unified Hospitals of North Buda
Budapest, Hungary, 1032
Semmelweis University Faculty of Medicine
Budapest, Hungary, 1082
University of Pecs, Institute of Oncology
Pecs, Hungary, 7624
Fejer County St. Gyorgy Hospital, Dept of Oncology
Szekesfehervar, Hungary, 8000
Poland
Ewa Pilecka Clinical Oncology Department and Outpatient Chemotherapy Unit, Bialostockie M.Sklodowska-Curie Oncology Centre in Bialystok
Bialystok, Poland, 15-027
Department of Chemotherapy, Health Care Facility of the Ministry of Internal Affairs and Administration and Warminsko-Mazurskie Oncology Centre in Olsztyn
Olsztyn, Poland, 10-228
Clinical Oncology Department and Day Hospitalization Unit, Independent Public Healthcare Facility T. Koszarowski Opolskie Oncology Centre in Opole
Opole, Poland, 45-060
Department of Urologic Oncology, Maria Sklodowska-Curie Institute of Oncology
Warsaw, Poland, 02-781
Puerto Rico
Fundacion de Investigacion de Diego
San Juan, Puerto Rico, 00927
Romania
Alba Lulia Emergency County Hospital
Alba Iulia, Romania, 510077
Dr Constantin Opris Emergency County Hospital
Baia Mare, Romania, 430031
S.C. Rapid Diagnosis Polyclinic SRL
Brasov, Romania, 500366
"Prof. Dr Th Burghele" Clinical Hospital
Bucharest, Romania, 50659
Fundeni Clinical Institute
Bucharest, Romania, 22328
SC Medisprof SRL
Cluj-Napoca, Romania, 400058
S.C. Provita 2000 SRL
Constanta, Romania, 900635
SC Oncolab SRL, Medical Oncology Dept
Craiova, Romania, 200385
Russian Federation
State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Clinical Oncology Center, Chemotherapy Department
Chelyabinsk, Russian Federation, 454087
State Medical Institution: Kursk Regional Oncological Center, Chemotherapy Dept
Kursk, Russian Federation, 305035
State Medical Institution of the City of Moscow: Municipal Clinical Hospital #57 under Moscow Department for Healthcare
Moscow, Russian Federation, 105077
Non-State Medical Institution: Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC Russian Railways, Chemotherapy Dpmt
Moscow, Russian Federation, 129128
Federal State Budget Institution: "Medical Radiological Research Center" under the Ministry of Health Care and Social Development of the Russian Federation
Obninsk, Russian Federation, 249036
St. Petersburg State Medical Institution: St. Petersburg Municipal Oncological Center, Department of Urologic Oncology
St Petersburg, Russian Federation, 197022
Russian Research Center for Radiology and Surgical Technologies
St. Petersburg, Russian Federation, 197758
Sponsors and Collaborators
Isis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Isis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01234025     History of Changes
Other Study ID Numbers: ISIS 183750-CS3
Study First Received: November 2, 2010
Last Updated: November 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Isis Pharmaceuticals:
Castrate-Resistant Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Docetaxel
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 29, 2014