| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hormone Refractory Prostate Cancer (HRPC) |
|
| MedDRA Classification |
| 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 |
Main objective :
The primary objective of the study is to estimate progression-free survival in patients with Hormone Refractory Prostate Cancer administered LY2181308 in combination with docetaxel compared to docetaxel alone. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives:
Assess the safety and adverse event profile of the combination
Characterize PSA kinetics and estimate PSA derived endpoints
Estimate time-to-event variables, such as overall survival time
Evaluate the pharmacokinetics of LY2181308 and docetaxel alone and in combination
Document objective response rate
Assess biomarker responses associated with LY2181308 and docetaxel combination
Evaluate patient reported outcomes with the validated Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) and the validated Brief Pain Inventory (BPI) |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Sample Banking Addendum H8Z-MC-JACR (1)
A Randomized Phase 2 Study of LY2181308 in Combination with Docetaxel plus Prednisone Versus Docetaxel Plus Prednisone in Hormone Refractory Prostate Cancer
This optional addendum is for the collection of plasma, blood, and DNA for future research. Participation in this research is limited to only the requirement that the study doctor or personnel collect a sample of your blood for DNA, serum, plasma 2 time(s). Eli Lilly and Company will receive and bank the sample(s) in a facility in the United States for scientific research.
The purpose of this study is to collect and bank samples from blood for DNA, serum, plasma for research aimed at associating naturally occurring differences in DNA or protein with risk for diseases such as cancer and/or the therapeutic response to LY2181308 sodium or other compounds/medications that you are taking during this study.
Although the Banked Sample(s) will be stored for research purposes, the sample(s) will be used only until the Banked Sample(s) collected in the trial is exhausted (gone). The patient's blood cells will not be made to grow indefinitely in the laboratory (immortalized).
|
|
| E.3 | Principal inclusion criteria |
Patients may be included in the study only if they meet all of the following criteria:
[1]Histologically or cytologically confirmed adenocarcinoma of the prostate, which is metastatic and cannot be resectable.
[2]Hormone refractory prostate cancer defined as progression under prior hormonal treatment with LHRH analogues or orchiectomy and anti-androgens, given either together or consecutively; and eligible to receive docetaxel and prednisone as first line chemotherapy treatment.
[3]Progressive disease is defined as PSA progression documented by 2 consecutive increased PSA values compared to a previous reference value. A total of 3 PSA measurements are required prior to registration into the trial. Each PSA level should be taken weekly to obtain the required 3 levels with the first PSA level used as the reference value. After a minimum of one week from the PSA reference value, a second PSA level should be collected to verify PSA increase. A third PSA value (i.e, the confirmation of elevated PSA) should occur a minimum of one week from the second PSA value. Because of potential fluctuation in PSA levels, the following process should be followed: If the third PSA value is decreased from the second, then a fourth PSA will be drawn within 7 days to confirm the increase from the initial reference value. Such cases will be discussed in detail with the Lilly clinical physician (Bubley et al. 1999).
[4]All patients must be withdrawn from anti-androgens such as Flutamide, Bicalutamide, or Nilutamide. If a patient has been on anti-androgens prior to start of study enrollment, they have to demonstrate a continued elevation of PSA for at least 4 weeks after withdraw of anti-androgen therapy (or 6 weeks for bicalutamide or depending on which anti-androgen they have been on) prior to registration on study.
[5]PSA greater than or equal to 5 ng/mL (Hybritech or equivalent) within 1 week prior to randomization.
[6] All patients are eligible regardless of measurability of disease by RECIST. Note: A patient may be eligible based on PSA response when other symptoms are present, such as pain or pleural effusion, etc. as defined by non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. However, only those patients with at least one unidimensionally measurable lesion meeting RECIST (RECIST; Therasse et al. 2000 ) criteria at baseline will be followed for objective response.
[7]Age ≥18 years.
[8]ECOG status 0-2 (see Protocol Attachment JACR.6).
[9]Castrate level of testosterone (≤0.5 ng/mL).
[10]Patients with medical castration with LHRH analogue must continue LHRH analogue.
[11]Adequate venous access.
[12]Adequate hematological functions as assessed by Hgb ≥10 g/dL; WBC ≥3.5 109/l, ANC ≥1.5 109/l , and platelets ≥100 109/l.
[13]Adequate liver function as assessed by bilirubin less than or equal to upper limit of the normal range (UNL) and AST ≤1.5 x UNL and ALT ≤1.5 x UNL.
[14]Adequate renal function as assessed by serum creatinine ≤1.5 xULN.
[15]Activated partial thromboplastin time (aPTT) ≤1.5xUNL (for those receiving warfarin, prothrombin time (PT) must be ≤1.5xUNL [or international normalized ratio (INR)≤1.3]).
[16]Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
|
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
[18]Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[19]Have previously completed or withdrawn from this study or any other study investigating LY2181308 sodium.
[20]Have known hypersensitivity to docetaxel or taxane therapy.
[21]Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out occult brain metastasis.
[22]Evidence of painful and/or destructive bone metastases for which radiation therapy, biophosphonates or bone-seeking radionucleides are considered necessary by the treating physician. Other bone metastases are allowed. If patients are stable on biphosphonates for 2 months or more, they may be enrolled if there is no other sign of progression.
[23]Had prior treatment with bone-seeking radionucleides (e.g., Rhenium, Samarium or Strontium) in the last 6 weeks prior to study enrollment, or radiotherapy involving more than 25% of marrow producing area. Radiotherapy less than 25% of marrow producing area should be stopped at least 14 days prior to study enrollment.
[24] Had treatment with estramustine, ketoconazole, finesteride, intravesical Bacillus Calmette-Guerin (BCG) application or any other non-approved substances with known impact on PSA within 30 days prior to study enrollment.
[25]Had prior hormonal manipulation with PC-SPES or other herbal remedies that contain hormonal products that can interfere with the conduct of the study within the last 6 weeks prior to entry on study.
[26]Concurrent treatment with other anti-cancer drugs .
[27]Known hypersensitivity to oligonucleotides or any component of the formulation.
[28]CVA or transient ischemic attack, deep venous thrombosis or myocardial infarction attacks within the past 6 months prior to entry on study.
(29): Active infection or known HIV.
[30]History of interstitial pneumonitis or pulmonary fibrosis.
[31]Patients with serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator).
[32]Patients with serious preexisting medical conditions including, but not limited to unstable angina, pulmonary embolism, uncontrolled hypertension and unmanageable bleeding risk (at the investigator’s discretion).
[33]Pre-existing neuropathy.
[34]Patients with a second primary malignancy that could affect interpretation of the results. NOTE: Patients with adequately treated carcinoma of the skin (excluding melanoma) and patients with a prior history of malignancy who have been disease-free for more than 5 years are eligible.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
In this study, the primary objective is to estimate progression-free-survival time (PFS) in patients with HRPC administered LY2181308 sodium in combination with docetaxel compared to docetaxel alone.
Progression-free survival is the primary efficacy outcome for this study. Kaplan-Meier analyses will be performed on the observed distributions of progression-free-survival (Kaplan and Meier 1958).
Parameter estimates of the PFS median and quartiles will be reported for each treatment group. Individual parameters, such as progression-free survival rate after specific time points (for example, after 6 months on treatment) will be estimated from the progression-free survival distribution. All parameter estimates will be quoted together with their 90% confidence limits.
The log-rank test will be performed to assess the treatment difference between the 2 groups.
The influence of prognostic and other baseline factors on progression-free-survival will be explored. For example, the effect of PSA levels, performance status or drug exposure will be explored.
|
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
Print
