- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03643107
Irofulven in AR-targeted and Docetaxel-Pretreated mCRPC Patients With Drug Response Predictor (DRP®)
Phase II Study of Irofulven in AR-targeted and Docetaxel-Pretreated Metastatic Castration-Resistant Prostate Cancer Patients, Who Have a Drug Response Predictor (DRP®) Indicating a High Likelihood of Response to Irofulven.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Copenhagen, Denmark, 2100
- Rigshospitalet, Dept. Of Oncology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Have a histologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (carcinomas with pure small-cell histology or pure high grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed)
- Surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL. For patients currently being treated with luteinizing hormone-releasing hormone (LHRH) agonists, i.e., patients who have not undergone an orchiectomy, therapy must be continued throughout the study
- Have evidence of disease progression after prior therapy for mCRPC:
- Disease progression after treatment with at least 1 but no more than 2 prior next-generation AR-targeted therapies (abiraterone acetate, enzalutamide, or investigational AR-targeted agent) for metastatic prostate cancer (treatment with the older anti-androgen therapies such as bicalutamide, flutamide, and nilutamide are not counted toward this limit), AND
- Disease progression after treatment with docetaxel for metastatic prostate cancer. Prior Docetaxel therapy administered for hormone-sensitive disease is permitted and is not counted toward this limit
- Disease progression after initiation of most recent therapy is based on any of the following criteria:
- Rise in PSA: a minimum of 2 consecutive rising levels, with an interval of ≥ 1 week between each determination. The most recent screening measurement must have been ≥ 1 ng/mL
- Transaxial imaging: new or progressive soft tissue masses on CT or MRI scans as defined by RECIST 1.1
- Radionuclide bone scan: at least 2 new metastatic lesions
- Signed informed consent obtained prior to initiation of any study-specific procedures or treatment.
- Age ≥ 18 years
- Life expectancy ≥ 3 months
- Performance status 0 - 1
- Have participated in the Irofulven screening protocol in which the Drug Response Predictor (DRP) outcome is measured as being in the upper limit of response (defined as being in the top 20%). Scaling can be modified depending on the clinical outcome.
- Adequate organ functions
- Hematological: absolute neutrophil count (ANC) >1.5 x 10E9/L, platelet count >100 x 10E9/L, hemoglobin ≥ 6.2 mmol/L
- Hepatic: Bilirubin within normal range, aspartate transaminase (AST) and alanine transaminase (ALT) ≥ 2.5 upper normal limit (UNL), albumin > 25 g/L
- Renal: creatinine clearance ≥ 30 mL/min (calculated according to the Cockcroft and Gault method)
- Recovered to grade 0 or 1 from any toxic effects of prior chemotherapy, radiotherapy
Exclusion Criteria:
- Prior external beam radiation therapy to >25% of the bone marrow
- Contraindication to the use of prednisolone (e.g. uncontrolled diabetes mellitus)
- Prior treatment with Irofulven.
- Ongoing treatment with a corticosteroid at a prednisolone-equivalent dose > 10 mg/day
- More than 1 prior treatment with either isotopes Sm or Sr, or radioisotope treatment or treatment with bisphosphonate agents or antibody treatment i.e., denosumab within 2 months prior to initiation of treatment with investigational Medicinal Product (IMP). Pre-existing treatment with bisphosphonate agents or denosumab is to be continued during the study
- Initiation of treatment with bisphosphonate agents or antibody treatment i.e., denosumab, within 4 weeks of study start. Pre-existing treatment with bisphosphonate agents or denosumab is to be continued during the study
- Treatment with coumarin derivatives and/or phenytoin most be discontinued and coagulation parameters most be within the normal range before treatment with Irofulven
- History of significant gastric or small bowel resection, malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may prevent compliance with oral drug administration
- Presence of any serious concomitant systemic disorders and/or psychiatric condition incompatible with the study (at the investigators discretion)
- History of retinopathy
- Presence of any active infection (at the investigators discretion).
- Central Nervous System Disease (CNS) disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Irofulven + Prednisolone 10mg
Irofulven will be administered as an intravenous dose of 0.45 mg/kg, over a 30-minute infusion period by venous access at day 1 and 8 of a three week cycle. Irofulven will be administered in combination with a daily dose of 10 mg orally administered prednisolone. |
Irofulven will be administered as an intravenous dose of 0.45 mg/kg, over a 30-minute infusion period by venous access at day 1 and 8 of a three week cycle. Irofulven will be administered in combination with a daily dose of 10 mg orally administered prednisolone. Irofulven will be administered as an intravenous dose of 0.45 mg/kg, over a 30-minute infusion period by venous access at day 1 and 8 of a three week cycle. Irofulven will be administered in combination with a daily dose of 10 mg orally administered prednisolone. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anti-tumor effect of Irofulven with prednisolone
Time Frame: one year
|
Objective response rate defined as complete response, partial response or stable disease > 9 weeks according to RECIST 1.1 for patients with measurable disease and defined as stable disease > 9 weeks according to Prostate Cancer Working Group 3 (PCWG3) for bone metastases
|
one year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of response (DOR)
Time Frame: one year
|
Time from documentation of tumor response to disease progression
|
one year
|
Radiologic progression free survival (rPFS)
Time Frame: one year
|
rPFS defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 9 weeks after enrolment, and/or progression in nodes or viscera on cross-sectional imaging, or death.
|
one year
|
Overall survival
Time Frame: one year
|
Time from enrolment until death from any cause.
|
one year
|
Prostate Specific Antigen (PSA) response
Time Frame: one year
|
≥ 50% decline in PSA compared to baseline in all patients according to PCWG3
|
one year
|
PSA response
Time Frame: one year
|
≥ 90% decline in PSA compared to baseline in all patients according to PCWG3
|
one year
|
Time to PSA progression
Time Frame: one year
|
PSA progression defined in accordance with PCWG3.
|
one year
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Prednisolone
- Irofulven
Other Study ID Numbers
- SMR-3165
- 2017-003549-72 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Castration-Resistant Prostate Cancer Patients
-
Myovant Sciences GmbHRecruitingMetastatic Castration-Resistant Prostate Cancer | Metastatic Castration-Sensitive Prostate Cancer | Non-Metastatic Castration-Resistant Prostate CancerUnited States
-
Janux TherapeuticsRecruitingProstate Cancer | Metastatic Castration-resistant Prostate Cancer | Castration Resistant Prostatic CancerUnited States, Australia
-
Gustave Roussy, Cancer Campus, Grand ParisCompletedMetastatic Castration Resistant Prostate Cancer PatientsFrance
-
Universität des SaarlandesRecruitingProstate Cancer Metastatic | Advanced Prostate Carcinoma | Castration Resistant Prostatic CancerGermany
-
Vadim S KoshkinEli Lilly and Company; Prostate Cancer FoundationActive, not recruitingCastration-Resistant Prostate Carcinoma | Stage IV Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage IVB Prostate Cancer AJCC v8 | Metastatic Castration-resistant Prostate Cancer | Metastatic Prostate Adenocarcinoma | Metastatic Castration-resistant Prostate CarcinomaUnited States
-
Rohan GarjeJanssen Scientific Affairs, LLCNot yet recruitingCastration-resistant Prostate Cancer | Metastatic Prostate Cancer | Metastatic Castration-resistant Prostate CancerUnited States
-
BAMF HealthRecruitingMetastatic Castration-resistant Prostate CancerUnited States
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Clarus TherapeuticsRecruitingProstate Cancer | Castration-resistant Prostate Cancer | Metastatic Castration-resistant Prostate CancerUnited States
-
Massachusetts General HospitalBayerCompletedProstate Cancer | Castration-resistant Prostate Cancer | Castration-resistant Prostate Cancer Metastatic to BoneUnited States
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.RecruitingMetastatic Castration-resistant Prostate CancerChina
Clinical Trials on Irofulven
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedEndometrial CancerUnited States, Canada
-
New Approaches to Brain Tumor Therapy ConsortiumNational Cancer Institute (NCI)CompletedBrain and Central Nervous System TumorsUnited States
-
Cancer Therapeutics Research GroupNational Cancer Institute (NCI)CompletedGastric CancerAustralia, Singapore, Hong Kong, Korea, Republic of
-
National Cancer Institute (NCI)CompletedMyelodysplastic Syndromes | LeukemiaUnited States
-
National Cancer Institute (NCI)CompletedOvarian Cancer | Fallopian Tube Cancer | Primary Peritoneal Cavity CancerUnited States
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)CompletedKidney CancerUnited States
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol SpecificUnited States, Canada, Australia
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States