Castrate-Resistant Prostate CancerPhase 1/2NCT01234025
Safety and Tolerability Study of ISIS EIF4E Rx in Combination With Docetaxel and Prednisone (CRPC)
A Phase 1/2 study testing ISIS EIF4E Rx, Prednisone and Docetaxel in people with Castrate-Resistant Prostate Cancer, run by Ionis Pharmaceuticals, Inc. at 38 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Castrate-Resistant Prostate Cancer
- What is being tested?
- ISIS EIF4E Rx, Prednisone and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 38 sitesin 6 countries
- Study dates
- Nov 2010to Dec 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
38 sites in 6 countries.
38 sites in 6 countries
United States11 sites
Gabrail Cancer Center
Canton, Ohio, 44718
Highlands Oncology Group
Fayetteville, Arkansas, 72703
Fort Range Cancer Center
Fort Collins, Colorado, 80528
Lakeland Regional Cancer Center
Lakeland, Florida, 33805
Central Baptist Hospital Clinical Research Center
Lexington, Kentucky, 40503
University of Miami, Miller School of Medicine - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
St. Luke's - Roosevelt Hospital Center
New York, New York, 10019
Norwalk Hospital- Whittingham Cancer Center
Norwalk, Connecticut, 06850
James P. Wilmont Cancer Center - University of Rochester Medical Center
Rochester, New York, 14642
San Bernardino Urological Associates
San Bernardino, California, 92404-4816
Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center
Shreveport, Louisiana, 71103
Romania8 sites
Alba Lulia Emergency County Hospital
Alba Iulia, 510077
Dr Constantin Opris Emergency County Hospital
Baia Mare, 430031
S.C. Rapid Diagnosis Polyclinic SRL
Brasov, 500366
Fundeni Clinical Institute
Bucharest, 22328
"Prof. Dr Th Burghele" Clinical Hospital
Bucharest, 50659
SC Medisprof SRL
Cluj-Napoca, 400058
S.C. Provita 2000 SRL
Constanța, 900635
SC Oncolab SRL, Medical Oncology Dept
Craiova, 200385
Russia7 sites
State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Clinical Oncology Center, Chemotherapy Department
Chelyabinsk, 454087
State Medical Institution: Kursk Regional Oncological Center, Chemotherapy Dept
Kursk, 305035
State Medical Institution of the City of Moscow: Municipal Clinical Hospital #57 under Moscow Department for Healthcare
Moscow, 105077
Non-State Medical Institution: Central Clinical Hospital #2 n.a. N.A. Semashko under OJSC Russian Railways, Chemotherapy Dpmt
Moscow, 129128
Federal State Budget Institution: "Medical Radiological Research Center" under the Ministry of Health Care and Social Development of the Russian Federation
Obninsk, 249036
St. Petersburg State Medical Institution: St. Petersburg Municipal Oncological Center, Department of Urologic Oncology
Saint Petersburg, 197022
Russian Research Center for Radiology and Surgical Technologies
Saint Petersburg, 197758
Poland6 sites
Ewa Pilecka Clinical Oncology Department and Outpatient Chemotherapy Unit, Bialostockie M.Sklodowska-Curie Oncology Centre in Bialystok
Bialystok, 15-027
Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego, Oddzial Onkologii Klinicznej
Grudziądz, 86-300
Department of Chemotherapy, Health Care Facility of the Ministry of Internal Affairs and Administration and Warminsko-Mazurskie Oncology Centre in Olsztyn
Olsztyn, 10-228
Clinical Oncology Department and Day Hospitalization Unit, Independent Public Healthcare Facility T. Koszarowski Opolskie Oncology Centre in Opole
Opole, 45-060
Department of Urologic Oncology, Maria Sklodowska-Curie Institute of Oncology
Warsaw, 02-781
Clinical Oncology Department/Chemotherapy Department, MAGODENT Non-Public Healthcare Facility, Branch Facility No. 4
Warsaw, 04-125
Hungary5 sites
Szent Janos Hospital and Unified Hospitals of North Buda
Budapest, 1032
Semmelweis University Faculty of Medicine
Budapest, 1082
National Institute of Oncology
Budapest, 1122
University of Pecs, Institute of Oncology
Pécs, 7624
Fejer County St. Gyorgy Hospital, Dept of Oncology
Székesfehérvár, 8000
About this study
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
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
- Being tested
- ISIS EIF4E Rx, Prednisone, Docetaxel
- Keywords
- Castrate-Resistant Prostate Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS EIF4E RxDrug
800 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle.
ISIS EIF4E RxDrug
1000 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle.
ISIS EIF4E RxDrug
(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.
PrednisoneDrug
5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle
DocetaxelDrug
75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Cohort 1 | Experimental | Not described Receives: Drug: ISIS EIF4E Rx; Drug: Prednisone; Drug: Docetaxel |
| Part 1 Cohort 2 | Experimental | Not described Receives: Drug: ISIS EIF4E Rx; Drug: Prednisone; Drug: Docetaxel |
| Part 2 Arm A | Experimental | Not described Receives: Drug: Prednisone; Drug: Docetaxel |
| Part 2 Arm B | Experimental | Not described Receives: Drug: ISIS EIF4E Rx; Drug: Prednisone; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Measured: At the end of each 21 day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2010 (estimated)
- Study startNov 2010
- Primary completionMay 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Castrate-Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01234025
- Sponsor's protocol ID
- ISIS 183750-CS3
- Status last verified
- Oct 2023
- First submitted
- 2 Nov 2010
- Last updated
- 6 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01234025
- Acronym / sponsor ID
- ISIS 183750-CS3
- Conditions
- Castrate-Resistant Prostate Cancer
- Keywords
- Castrate-Resistant Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- May 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 4 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 Cohort 1 | Experimental | Drug: ISIS EIF4E Rx, Drug: Prednisone, Drug: Docetaxel |
| Part 1 Cohort 2 | Experimental | Drug: ISIS EIF4E Rx, Drug: Prednisone, Drug: Docetaxel |
| Part 2 Arm A | Experimental | Drug: Prednisone, Drug: Docetaxel |
| Part 2 Arm B | Experimental | Drug: ISIS EIF4E Rx, Drug: Prednisone, Drug: Docetaxel |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- 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:
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISIS EIF4E Rx800 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle. | Drug | Part 1 Cohort 1 |
| ISIS EIF4E Rx1000 mg ISIS EIF4E Rx administered as a 3-hour intravenous infusion on Days 1, 8 and 15 of each 21 day cycle. | Drug | Part 1 Cohort 2 |
| 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 | Part 2 Arm B |
| Prednisone5 mg administered orally twice daily on days 1, 8, 15 and 22 of each cycle | Drug | Part 1 Cohort 1, Part 1 Cohort 2, Part 2 Arm A, Part 2 Arm B |
| Docetaxel75 mg/m2 administered as a 1-hour intravenous infusion on day 1 of each cycle | Drug | Part 1 Cohort 1, Part 1 Cohort 2, Part 2 Arm A, Part 2 Arm B |
Primary outcome
Progression free survival
Time frame: At the end of each 21 day cycle
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
38 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ISIS EIF4E Rx, Prednisone and Docetaxel in people with Castrate-Resistant Prostate Cancer, run by Ionis Pharmaceuticals, Inc. at 38 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Romania, Russia, Poland, Hungary and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: At the end of each 21 day cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.