E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The effect of high dose intravenous weekly vitamin c infusion in castration resistant human prostate cancer |
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E.1.1.1 | Medical condition in easily understood language |
To evaluate if high dose intravenous vitamin c once weekly has effect on advanced prostate cancer (in the stage when castration treatment is no longer sufficient to keep the disease under control) |
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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 | 14.1 |
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) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 (Prostate specific antigene) PSA response to high dose, weekly intraveneous vitamin C(VC) treatment after 12, 20, 25 and 52 weeks in subjects with castration resistant prostate cancer. |
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E.2.2 | Secondary objectives of the trial |
Median survival in subjects vs. patients receiving Docetaxel (def. survival from time of hormone refractory disease until death) ECOG performance status before treatment and at 12, 20, 26 and 52 weeks EORCT Core and P25 changes at week 12 Extent of osseous metastasis using bone scan before treatment and at 12, 26 and 52 weeks Alkaline phosphatase changes before treatment and at 12, 20, 26 and 52 weeks se-Ca2+ changes before treatment and at 12, 20, 26 and 52 weeks Whole genome gene expression changes before treatment and at 12 and possibly 20 weeks Changes in oxidative DNA-damage before treatment and at 12 and possibly 20 weeks
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Gender: male Age > 18 years Biopsy verified PCa Gleason sum >6 PSA >10 ng/ml (no PSA-negative cancers) No predominant neuro-endocrine differentiation Metastatic PCa defined as extra nodal (visceral) metastasis and/or bone lesions on radionucleotide bone scan. Hormone refractory disease defined as at least 2 increases in PSA with at least 10% increases a least 1 week apart within the last 6 months. Se-testosterone must be at castrate level The patients must have received prior hormonal ablation treatment consisting of either orchiectomy or LHRH-antagonists/agonists with the optional addition of non-steroidal anti-androgens(bicalutamid). Any LHRH agonist or antagonist treatment must be continued during the protocol. Discontinuation of non-steroidal anti-androgen must be attempted prior to enrolment. ECOG performance status 0-2 Negative test-screen regarding G-6-P DH deficiency. Normal to near normal renal function (se-creatinium <200µM and no history of major impaired renal function) Bisphophonate and prednisone therapy can be continued during the project External beam radiation of extraprostatic metastases allowed
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E.4 | Principal exclusion criteria |
Adverse and intolerable side effects to infusions (see “side effects…” paragraph) Deteriorating physical condition not allowing for outpatient infusions Physician or patient opting for chemotherapy or other interventional therapy Synchronous cancers (non-melanoma skin cancer excluded) No chemotherapy for PCa allowed during the treatment period (week 1-12 (20)) Allergies to vitamin C or additives in project medications History of oxalate kidney stone History of hemochromatosis Major surgery for the past 4 weeks (def.: surgical procedures requiring >2 days of admittance) Active cardiac disease (CCS >2, NYHA >2), myocardial infarction for the past 6 months Participation in clinical trials involving administration of any pharmaceutical drugs whilst receiving the VC infusions.
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E.5 End points |
E.5.1 | Primary end point(s) |
PSA response to treatment with IMP |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
A: PSA response to treatment with IMP (8 week extension arm)
B: Bone metastases changes
C: bALP changes u-NTX changes PINP changes 8-oxo-guanine changes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A: 20 weeks
B: 12,26 and 52 weeks
C: 12,20,26 and 52 weeks |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
gene expression profiling |
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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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 |