| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| For the treatment of metastatic androgen independent prostate cancer |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10029104 |
| E.1.2 | Term | 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 evaluate the efficacy of weekly DN-101 in combination with weekly docetaxel (the ASCENT regimen) in the treatment of metastatic androgen independent prostate cancer as measured by duration of survival. |
|
| E.2.2 | Secondary objectives of the trial |
To determine the efficacy of ASCENT regimen as measured by thromboembolic event (TE) rate.
To determine the efficacy of ASCENT regimen as measured by duration of skeletal-related event (SRE)-free survival. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1) Signed informed consent prior to beginning protocol specific procedures. Subject must be capable of providing informed consent.
2) Histopathologically or cytologically proven adenocarcinoma of the prostate.
3) Metastatic prostate adenocarcinoma documented by computed tomography (CT), magnetic resonance imaging (MRI), or bone scan. A bone scan is required within 4 weeks prior to study randomization as baseline measurement.
4) Prior therapy by androgen ablation either by orchiectomy and/or luteinizing hormone releasing hormone (LHRH) agonists or antagonists.
5) Subjects who have received any of the following additional hormonal therapies remain eligible:
• Anti-androgens
• Monotherapy with estramustine (> 4 weeks must have elapsed since completion of prior estramustine therapy with full recovery from any side effects)
• Prior therapy with corticosteroids and/or ketoconazole
• Other hormonal agents for therapy of prostate cancer
6) If a subject has been treated or is currently receiving treatment with bisphosphonates, the subject is eligible for the study and the therapy can continue at investigator’s discretion.
7) Maintaining castrate status: Subjects who have not undergone surgical orchiectomy should continue on medical therapies with a LHRH agonist or LHRH antagonist to maintain castrate levels of serum testosterone.
8) Documented progression while on androgen ablation therapy detected by rising PSA and/or imaging. Progression for study eligibility is defined as at least one of the following (Bubley et al, 1999):
• PSA progression: An elevated PSA ( ≥ 5 ng/mL) which has risen serially from baseline (#1) on two occasions each at least one week apart. If the confirmatory PSA (#3) is less than PSA value #2, then a subsequent test for rising PSA (#4) is required to be taken and must be greater than the 2nd measure (#2). .
• Progression of target lesions: change in size of lymph nodes or parenchymal masses, bidimensional or unidimensional, on PE or x-rays
• Progression of non-target lesions (except bone)
• Bone scan progression: worsening bone scan as evidenced by the appearance of two or more new skeletal lesions that are not felt to be consistent with tumor flare. Subjects whose sole evidence of progression is on bone scan must also have a PSA > 5 ng/mL.
9) Prior radiation therapy to less than 25% of the bone marrow only (excluding whole pelvic irradiation) is allowed if at least four weeks have elapsed since completion of therapy.
10) Prior surgery is allowed if at least four weeks have elapsed since completion of the surgery.
11) Life expectancy ≥ 3 months.
12) Willingness to discontinue prohibited concomitant medications or diet supplements including calcium supplements, pharmacologic doses of vitamin D or derivatives, ketoconazole or related drugs, and systemic steroids.
13) ECOG Performance Status ≤ 2.
14) Age ≥ 18 years.
15) Laboratory requirements:
• Hematology:
o absolute neutrophil counts (ANC) ≥ 1.5 x 109/L
o hemoglobin ≥ 10 g/dL (Erythropoietin and darbopoetin use is allowed but red blood cell transfusion to upgrade the hemoglobin level is not allowed)
o platelets ≥ 100 x 109/L
• Hepatic function:
o total bilirubin < the upper-normal limit (ULN)
o alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
≤ 1.5 times the ULN
• Renal function:
o serum creatinine concentration ≤ 1.5 times the ULN
o serum calcium ≤ the ULN
• Testosterone:
o testosterone < 50 ng/mL or 173 nmol/L
16) Subjects who have received prior therapy with vaccines or other immunotherapy remain eligible for study participation. |
|
| E.4 | Principal exclusion criteria |
1) Prior cytotoxic chemotherapy, except monotherapy with estramustine.
2) Prior chemotherapy with docetaxel.
3) Prior isotope therapy (e.g., strontium-89, samarium-153, etc.).
4) Prior malignancy other than prostate cancer except the following: adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the subject has been disease-free for > 5 years.
5) Known brain or leptomeningeal involvement. Subjects with stable treated epidural lesions are eligible for participation in the study.
6) History of cancer-related hypercalcemia, known hypercalcemia, or vitamin D toxicity.
7) Active uncontrolled infection.
8) Active symptomatic peptic ulcer disease, unstable diabetes mellitus or other contraindications for the use of corticosteroids.
9) Other serious illness or medical condition that in the opinion of the Investigator would be expected to interfere with the subject’s ability to receive study treatment or to comply with study procedures.
10) Symptomatic peripheral neuropathy ≥ Grade 2 according to the NCI-CTCAE version 3.0.
11) Hypersensitivity to drugs formulated with polysorbate-80 (a component of the docetaxel formulation).
12) Hypersensitivity to calcitriol.
13) Prior investigational therapy within the 28 days prior to randomization.
14) Prior use of calcitriol (e.g. generic calcitriol, Rocaltrol®, Calcijex®, and DN-101) or paricalcitol (Zemplar®) within 28 days prior to randomization.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is duration of survival.
|
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| q3 weekly docetaxel plus prednisone |
|
| 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 | 50 |
| 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 | 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
|
| The end of trial will be when the primary efficacy analysis occurs. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
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