Metastatic Castration-Resistant Prostate Cancer (mCRPC) prostate cancer
Conditions
Interventions
Arm A: Docetaxel 75 mg/m2 will be administered IV every three weeks for 10
doses. Prednisone will be given at a dose of 5mg orally twice daily.
Dexamethasone will be given per institutional practice
Sponsors
Memorial Sloan Kettering Cancer Center
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria: • Willing and able to provide, or have a legally authorized representative provide, written informed consent (ICF) and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. • Males 18 years of age and above • Histological or cytological proof of prostate cancer • Documented progressive mCRPC based on at least one of the following criteria: 1. PSA progression defined as a minimum of 2 rising PSA levels with a minimum of a 1 week interval between each determination. A minimum PSA of 1.0 ng/m is required for study entry. 2. Soft-tissue progression defined as an increase >= 20% in the sum of the LD of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions. 3. Progression of bone disease (evaluable disease) or two or more new bone lesions by bone scan. • Two or more bone lesions defined by nuclear bone scan • ECOG 0- 1 • Normal organ function with acceptable initial laboratory values within 14 days of randomization • Subjects must agree to use a medically acceptable method of birth control or sexual abstinence for the duration of the study, including 6 months after the last dose of study drug. Sperm donation is prohibited during the study and for 6 months after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent. • Serum testosterone
Exclusion criteria
Exclusion criteria: Exclusion Criteria: • Received any other investigational therapeutic agents or other anticancer therapies within 2 weeks or 5 half-lives, whichever is shorter, prior to randomization. • Received external beam radiotherapy within the 2 weeks prior to randomization. • Has an immediate need for external beam radiotherapy. • Has received any other systemic investigational or anti-cancer radiopharmaceutical in the past. • Has received any prostate cancer directed chemotherapy in the castration resistant setting • Has received > 6 prior doses of docetaxel in the castration sensitive setting. Subjects who have received up to 6 prior doses of docetaxel in the castration sensitive setting are permitted if they have not experienced disease progression within 36 weeks of last treatment with docetaxel. • Has received four or more systemic anticancer regimens for mCRPC. o Treatment with docetaxel or abiraterone for non-castrate metastatic disease is permissible and does not count towards the lines of therapy for mCRPC o A 'line' is a regimen. Combinations of hormones and other types of therapies count as single lines. • Has known Grade >=3 non-hematological docetaxel-related toxicities or docetaxel toxicity related dose interruption or discontinuation. • Has received blood transfusions or growth factors within the last 4 weeks prior to randomization. • Symptomatic nodal disease (i.e., scrotal, penile, or leg edema). • Has visceral metastases with > 3 lung and/or liver metastases or individual lesion >2 cm, as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8 weeks prior to randomization. • Symptomatic loco-regional disease that causes ongoing Grade 3 or Grade 4 urinary or rectal symptoms. • Subjects with a second malignancy with a risk of recurrence >30% within the next 3 years. Non-melanoma skin cancers, non-invasive bladder cancers and other in-situ or non-invasive malignancies are permitted while on study. • Has imminent or established cord compression based on clinical findings and/or MRI. • Known bone marrow dysplasia • Has received any of the following in the 4 weeks prior to randomization: 5-alpha-reductase inhibitors, natural hormonally active foods (e.g., phytoestrogens) or other food supplements known to alter PSA in humans. • Is receiving ongoing treatment with herbal medications that are known in humans to alter PSA or the natural history of prostate cancer. Subjects must discontinue any such herbal medications prior to the first dose of study drug Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including but not limited to: o Uncontrolled infection o NYHA III or IV heart failure o Crohn's disease or those with ulcerative colitis who have not undergone a colectomy o Known active infection with HIV, Hepatitis B or Hepatitis C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The overall survival comparison between treatments will be evaluated at each interim analysis and the final analysis using the stratified logrank test. The stratification factors are: • Prior docetaxel for castrate sensitive disease • Visceral disease (presence or absence) | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare: a. Radiographic progression free survival as defined in PCWG3 criteria b. Symptomatic Skeletal event free survival c. Time to total alkaline phosphatase (ALP) progression d. On-treatment alterations in quality of life as assessed by FACT-P, BPI, and BFI measures between subjects who receive docetaxel with those who receive docetaxel and radium-223 To determine if there is excessive: e. Febrile neutropenia in subjects treated with docetaxel plus radium-223 f. Treatment discontinuation in subjects who are on their fourth line of therapy Correlative/Exploratory/Tertiary Objectives To evaluate: a. On treatment alterations in PSA b. Time to first SSE c. On-treatment alterations in urine C-telopeptide (UCTx1), N-terminal propeptide of procollagen type 1 (P1NP), and pyridinoline cross-linked carboxyterminal telopeptide (ICTP) d. Total ALP response e. On-treatment alterations in CTC enumeration, and AR-V7 characterization f. On-treatment alterations in ctDNA g. On-treatment changes in automated Bone Scan Index (aBSI) | — |
Countries
Netherlands
Outcome results
None listed