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

NCT ID: NCT01234025

Last Updated: 2023-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 113 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2013-12-31

Brief Summary

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.

Conditions

Castrate-Resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 Cohort 1

Group Type: EXPERIMENTAL

ISIS EIF4E Rx

Intervention Type: DRUG

800 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle.

Prednisone

Intervention Type: DRUG

5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle

Docetaxel

Intervention Type: DRUG

75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle

Part 1 Cohort 2

Group Type: EXPERIMENTAL

ISIS EIF4E Rx

Intervention Type: DRUG

1000 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle.

Prednisone

Intervention Type: DRUG

5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle

Docetaxel

Intervention Type: DRUG

75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle

Part 2 Arm A

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle

Docetaxel

Intervention Type: DRUG

75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle

Part 2 Arm B

Group Type: EXPERIMENTAL

ISIS EIF4E Rx

Intervention Type: DRUG

(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.

Prednisone

Intervention Type: DRUG

5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle

Docetaxel

Intervention Type: DRUG

75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Prednisone

5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle

Intervention Type: DRUG

Docetaxel

75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle

Intervention Type: DRUG

Eligibility 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:

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

San Bernardino Urological Associates

San Bernardino, California, United States

Fort Range Cancer Center

Fort Collins, Colorado, United States

Norwalk Hospital- Whittingham Cancer Center

Norwalk, Connecticut, United States

Lakeland Regional Cancer Center

Lakeland, Florida, United States

University of Miami, Miller School of Medicine - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Central Baptist Hospital Clinical Research Center

Lexington, Kentucky, United States

Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center

Shreveport, Louisiana, United States

St. Luke's - Roosevelt Hospital Center

New York, New York, United States

James P. Wilmont Cancer Center - University of Rochester Medical Center

Rochester, New York, United States

Gabrail Cancer Center

Canton, Ohio, United States

Szent Janos Hospital and Unified Hospitals of North Buda

Budapest, , Hungary

Semmelweis University Faculty of Medicine

Budapest, , Hungary

National Institute of Oncology

Budapest, , Hungary

University of Pecs, Institute of Oncology

Pécs, , Hungary

Fejer County St. Gyorgy Hospital, Dept of Oncology

Székesfehérvár, , Hungary

Ewa Pilecka Clinical Oncology Department and Outpatient Chemotherapy Unit, Bialostockie M.Sklodowska-Curie Oncology Centre in Bialystok

Bialystok, , Poland

Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego, Oddzial Onkologii Klinicznej

Grudziądz, , Poland

Department of Chemotherapy, Health Care Facility of the Ministry of Internal Affairs and Administration and Warminsko-Mazurskie Oncology Centre in Olsztyn

Olsztyn, , Poland

Clinical Oncology Department and Day Hospitalization Unit, Independent Public Healthcare Facility T. Koszarowski Opolskie Oncology Centre in Opole

Opole, , Poland

Department of Urologic Oncology, Maria Sklodowska-Curie Institute of Oncology

Warsaw, , Poland

Clinical Oncology Department/Chemotherapy Department, MAGODENT Non-Public Healthcare Facility, Branch Facility No. 4

Warsaw, , Poland

Fundacion de Investigacion de Diego

San Juan, , Puerto Rico

Alba Lulia Emergency County Hospital

Alba Iulia, , Romania

Dr Constantin Opris Emergency County Hospital

Baia Mare, , Romania

S.C. Rapid Diagnosis Polyclinic SRL

Brasov, , Romania

Fundeni Clinical Institute

Bucharest, , Romania

"Prof. Dr Th Burghele" Clinical Hospital

Bucharest, , Romania

SC Medisprof SRL

Cluj-Napoca, , Romania

S.C. Provita 2000 SRL

Constanța, , Romania

SC Oncolab SRL, Medical Oncology Dept

Craiova, , Romania

State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Clinical Oncology Center, Chemotherapy Department

Chelyabinsk, , Russia

State Medical Institution: Kursk Regional Oncological Center, Chemotherapy Dept

Kursk, , Russia

State Medical Institution of the City of Moscow: Municipal Clinical Hospital #57 under Moscow Department for Healthcare

Moscow, , Russia

Non-State Medical Institution: Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC Russian Railways, Chemotherapy Dpmt

Moscow, , Russia

Federal State Budget Institution: "Medical Radiological Research Center" under the Ministry of Health Care and Social Development of the Russian Federation

Obninsk, , Russia

St. Petersburg State Medical Institution: St. Petersburg Municipal Oncological Center, Department of Urologic Oncology

Saint Petersburg, , Russia

Russian Research Center for Radiology and Surgical Technologies

Saint Petersburg, , Russia

Countries

United States; Hungary; Poland; Puerto Rico; Romania; Russia

Other Identifiers

ISIS 183750-CS3

Identifier Type: -

Identifier Source: org_study_id