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 Irofulve

Phase 1

Conditions: AR-targeted and Docetaxel-Pretreated Metastatic Castration-Resistant Prostate Cancer
MedDRA version: 20.0Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-003549-72-DK

Lead Sponsor: Oncology Venture Aps

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: 27

Inclusion Criteria

In order to participate in this study the subjects must meet all of the following inclusion criteria:
1. 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)
2. 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
3. Have evidence of disease progression after prior therapy for mCRPC:
a.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
b. 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
4. Signed informed consent obtained prior to initiation of any study-specific procedures or treatment
5. Age = 18 years
6. Life expectancy = 3 months
7. Performance status 0 - 1
8. Drug response predictor (DRPTM) in the upper likelihood of response (DRP value is available via the screening procedure performed by Medical Prognosis Institute)
9. Adequate organ functions
a. Hematological: absolute neutrophil count (ANC) >1.5 x 109/L, platelet count >100 x 109/L, hemoglobin > 6,2 mmol/L
b. Hepatic: Bilirubin within normal range, aspartate transaminase (AST) and alanine transaminase (ALT) <2.5 UNL, albumin > 25 g/L
c. Renal: creatinine clearance >30 mL/min (calculated according to the Cockcroft and Gault method)
10. Recovered to grade 0 or 1 from any toxic effects of prior chemotherapy, radiotherapy

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion Criteria

In order to participate in the study subjects must not meet any of the following exclusion criteria:
1. Prior external beam radiation therapy to >25% of the bone marrow
2. Contraindication to the use of prednisolone (e.g. uncontrolled diabetes mellitus)
3. Prior treatment with Irofulven.
4. Ongoing treatment with a corticosteroid at a prednisolone-equivalent dose > 10 mg/day
5. More than 1 prior treatment with either 153Sm or 89Sr, or radioisotope treatment or treatment with bisphosphonate agents or antibody treatment i.e., denosumab within 2 months prior to initiation of treatment with IMP. Pre-existing treatment with bisphosphonate agents or denosumab is to be continued during the study
6. 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
7. Treatment with coumarin derivatives and/or phenytoin most be discontinued and coagulation parameters most be within the normal range before treatment with Irofulven
8. 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
9. Presence of any serious concomitant systemic disorders and/or psychiatric condition incompatible with the study (at the investigator’s discretion)
10. History of retinopathy
11. Presence of any active infection (at the investigator’s discretion).
12. CNS disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures