| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chemo-naïve metastatic prostate cancer subjects with documented rising Prostate Specific Antigen (PSA) or documented Progressive Disease (PD) following hormonal therapy |
|
| E.1.1.1 | Medical condition in easily understood language |
| Cancer affecting cells in the prostate gland and spreading to other parts of the body, particularly the bones and lymph nodes |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10036909 |
| E.1.2 | Term | Prostate cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the Overall Survival (OS) benefit of docetaxel and prednisone with and without lenalidomide as first-line therapy in chemo-naïve metastatic Castrate Resistant Prostate Cancer (CRPC) subjects. |
|
| E.2.2 | Secondary objectives of the trial |
Progression-Free Survival (PFS)
Objective Response Rate
Safety of lenalidomide in combination with docetaxel and prednisone |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Understand and voluntarily sign an Informed Consent Form (ICF)
2. Males ≥ 18 years of age at the time of consent
3. Able to adhere to the study visit schedule and requirements of the protocol
4. ECOG performance status of ≤ 2
5. Life expectancy of ≥ 12 weeks
6. Willingness to participate in HRQoL and pain assessments and have ability to complete PRO and pain assessments without assistance or with minimal assistance from trained site personnel and/or caregiver
7. Effective castration (defined as serum testosterone levels < 50 ng/dL):
- Primary testicular androgen suppression (e.g., LHRH agonists or antagonists) should be continued during study treatment for subjects who have not had a bilateral orchiectomy.
8. Histologically confirmed adenocarcinoma of the prostate and:
- Prostate cancer that is unresponsive or refractory to hormonal therapy AND
- Metastatic disease confirmed by bone scan, CT scan, MRI, or X-Ray
9. Have documented disease progression while receiving or following hormonal therapy for treatment of advanced prostate cancer despite castrate levels of serum testosterone due to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist as determined by at least one of the following criteria:
- Serum PSA level ≥ 2ng/mL that has increased from a reference value (the last value immediately prior to the first rise) on at least two consecutive PSA measurements obtained at least 1 week apart prior to randomization
- Progression of measurable disease
- Measurable disease is defined as at least one measurable lesion ≥ 10 mm in the longest diameter by CT or MRI (or 20 mm by chest X-ray) and/or lymph nodes ≥ 15 mm short axis
- Progression of measurable disease is defined as an increase of ≥ 20% in the sum of the diameters of target lesions from the time of maximal regression with an absolute increase of ≥ 5mm, OR the appearance of ≥ 1 new lesion
- Unequivocal progression of non-measurable disease
- Non-measurable disease is defined as all lesions < 10mm in the longest diameter or pathological lymph nodes ≥10 mm to < 15 mm short axis
- Unequivocal progression of existing lesions is defined as an increase in overall disease burden based on the change in non-measurable disease that is comparable in magnitude to the increase that would be required to declare disease progression for measurable disease
- Two or more new bone lesions as detected by bone scan
10. All subjects:
- Must be counseled about pregnancy precautions and risks of fetal exposure. See Appendix 21.7.2 Lenalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, and Appendix 21.7.3 Lenalidomide Education and Counseling Guidance Document
- Must agree to use a condom during sexual contact with a female of childbearing potential (FCBP), even if they have had a vasectomy, while participating in this study, during dose interruptions, and for a period of 28 days following the last dose of study drug
- Must agree to refrain from donating semen or sperm while participating in this study and for a period of 28 days following the last dose of study drug.
- Must agree to refrain from donating blood or plasma while participating in this study and for a period of 28 days following the last dose of study drug
- Must agree not to share study drug with anyone during participation in the study
|
|
| E.4 | Principal exclusion criteria |
1. A history of clinically significant (as determined by the investigator) medical, surgical, or psychiatric disease that would place the subject at an unacceptable risk for study entry
2. Prior therapy with thalidomide, lenalidomide (CC-5013) or pomalidomide (CC-4047)
3. Prior chemotherapy for prostate cancer
- Treatment with estramustine will be allowed if last treatment is more than 28 days prior to randomization, and subject has recovered from side effects
- Adjuvant and/or neoadjuvant treatment will be allowed if completed > 3 years prior to randomization and provided the treatment was a non-taxane based regimen
4. Use of any other experimental drug or therapy within 28 days prior to randomization.
5. Prior radiation to ≥ 30% of bone marrow as determined by review of Appendix 21.4 and/or consultation with radiation specialist
6. Any other radiation therapy within 28 days prior to randomization
- Subjects receiving prior radiation must have recovered from acute toxicity or any side effects due to radiation treatments prior to randomization
7. Prior use of Strontium-89 at any time or Samarium-153 within 56 days prior to randomization.
8. Surgery within 28 days prior to randomization (minimally invasive procedures for the purpose of diagnosis or staging of the disease are permitted).
9. Concurrent antiandrogen therapy as follows:
- Treatment with antiandrogens (e.g., flutamide), aminoglutethimide, megestrol or diethylstilbestrol (DES) must be discontinued at least 4 weeks prior to randomization
- Treatment with bicalutamide and nilutamide must be discontinued at least 6 weeks prior to randomization
- Subjects exhibiting clinical symptoms and/or radiologic evidence of rapidly progressive disease will be allowed to initiate treatment if in the clinical judgment of the investigator a 4- or 6-week delay for anti-androgen washout would compromise the health and safety of the study subject
- Subjects without prior orchiectomy should continue treatment with LHRH agonists or antagonists
- Bisphosphonates may be used if treatment was initiated at least 28 days prior to randomization
- Concurrent therapy with steroids or hormones for adrenal insufficiency or nondisease-related conditions (e.g., insulin for diabetes) are allowed
10. Any of the following laboratory values:
- Hemoglobin < 9 g/dL
- Absolute neutrophil count (ANC) < 1.5 x 10^9 cells/L
- Platelet count < 100 x 10^9 cells/L
- Creatinine clearance < 50 mL/min by Cockcroft-Gault formula
- Total bilirubin > 1.0 x ULN
- Serum aspartate amino transaminase (AST)/SGOT and/or alanine transaminase (ALT)/SGPT > 1.5 x ULN concomitant with alkaline phosphatase > 2.5 x ULN
11. Must not have had significant active cardiac disease within the previous 6 months including:
- History of uncontrolled hypertension (i.e., BP > 160/90 mmHg) despite anti-hypertensive therapy
- New York Heart Association class II-IV congestive heart failure
- Unstable angina
- Myocardial infarction
12. Clinically significant peripheral arterial occlusive disease (i.e., claudication on less than 1 block)
13. Thrombotic or thromboembolic events within the past 6 months, including any of the following:
- Deep Vein Thrombosis or Pulmonary Embolism within the preceding 6 months
- Transient ischemic attack
- Cerebrovascular accident
- Any other arterial thrombotic event
14. Current or history of peripheral neuropathy of ≥ grade 2
15. History of severe hypersensitivity reaction to drugs formulated with polysorbate 80
16. Paraplegia
17. History of symptomatic central nervous system (CNS) or brain metastases
- Subjects who have remained asymptomatic for 90 days and demonstrate no active CNS involvement as shown by CT, MRI, or lumbar puncture are not excluded
- If required, CT, MRI, or lumbar puncture should be performed during the screening process
18. History of malignancies other than prostate cancer within the past 5 years, with the exception of treated basal cell/squamous cell carcinoma of the skin
19. Concurrent use of alternative cancer therapies during study treatment. Subjects taking alternative therapies for cancer must stop taking these therapies prior to randomization. Alternative therapies are not allowed during study treatment. This includes alternative therapies such as, but not limited to:
- Saw Palmetto
- DHEA
- Lycopene
- PC -SPES (all types)
- Vitamins and/or dietary supplements used at therapeutic doses for treatment of prostate cancer including:
- Vitamin D
- Selenium
- The use of dietary supplements at daily recommended levels or for vitamin/ mineral deficiencies is not an exclusion criterion
- Citrus pectin |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Overall Survival
OS is defined as time from randomization to death. All deaths, regardless of the cause of death, will be included. All subjects who are lost to the follow-up prior to the end of the trial or who are withdrawn from the trial will be censored at the time of last contact. Subjects who are still being treated will be censored at the last available date the subject is known to be alive or clinical cut-off date whichever is earlier. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
OS will be evaluated from Cycle 1 day 1 until subject death.
Subjects will be followed for survival throughout the study treatment
and every 90 days after treatment phase discontinuation for up to 5
years or until all subjects have died.
An interim efficacy analysis based on OS will be performed when 468
events have occurred and all subjects have been randomized. The final primary analysis for overall survival is planned once 624 events are observed (after aprox 4 years since FPI) |
|
| E.5.2 | Secondary end point(s) |
•Progression-Free Survival (PFS)
•Objective Response Rate
•Safety of lenalidomide in combination with docetaxel and prednisone |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• PFS: Cycle 1 day 1 until disease progression. PFS will be assessed on Day 1 of each third cycle (starting with Cycle 4, Day 1), and at treatment phase discontinuation.
• ORR: Cycle 1 day 1 until best measurable response. Assessments will be scheduled for Day 1 of each third cycle, starting with Cycle 4, Day 1, and at Treatment Phase discontinuation.
• Safety: baseline until 28 days after last study dose. Safety review of
the study after 100 subjects have completed 2 treatment cycles or
prematurely withdrawn from the study. Ongoing safety assessments will be performed every 6 months until the final subject enrolled has
completed either 2 treatment cycles or pre-maturely withdrawn from the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 110 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Australia |
| Israel |
| Mexico |
| Russian Federation |
| South Africa |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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