Irofulven in AR-targeted and Docetaxel-Pretreated mCRPC Patients With Drug Response Predictor (DRP®)

NCT03643107 | Completed Phase 2

• 2 other identifiers: SMR-31652017-003549-72
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The study seek to evaluate the anti-tumor effect after treatment of Irofulven in combination with prednisolone in patients who progressed on androgen receptor(AR)-targeted therapy and Docetaxel-Pretreated Metastatic Castration-Resistant Prostate Cancer Patients. A drug response predictor (DRP®) biomarker in prostate cancer patients will identify patients likely to respond to and benefit from treatment with Irofulven.

Conditions

Metastatic Castration-Resistant Prostate Cancer Patients

Keywords

Drug Response Prediction (DRP)

Outcome Measures

Primary Outcomes (1)

• Anti-tumor effect of Irofulven with prednisolone

  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 Outcomes (6)

• Duration of response (DOR)

  one year

• Radiologic progression free survival (rPFS)

  one year

• Overall survival

  one year

• Prostate Specific Antigen (PSA) response

  one year

• PSA response

  one year

Study Arms (1)

Irofulven + Prednisolone 10mg

EXPERIMENTAL

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.

Drug: Irofulven; Combination Product: Prednisolone 10 mg

Interventions

Irofulven DRUG

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 + Prednisolone 10mg

Prednisolone 10 mg COMBINATION_PRODUCT

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 + Prednisolone 10mg

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Allarity Therapeutics: lead
• Smerud Medical Research International AS: collaborator
• Lantern Pharma Inc.: collaborator

Study Sites (1)

Rigshospitalet, Dept. Of Oncology

Copenhagen, 2100, Denmark

Location

MeSH Terms

Interventions

irofulven; Prednisolone

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 22, 2018
• Study Start: October 17, 2018
• Primary Completion: October 1, 2021
• Study Completion: August 1, 2022
• Last Updated: January 23, 2025

Record last verified: 2025-01

Locations

DK (1)