E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients suffering from histopathologically documented Mycosis Fungoides, clinical stage Ib-IIa |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028500 |
E.1.2 | Term | Mycosis fungoides NOS |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To adress whether adding Bexarotene (TargretinTM) to the standard PUVA treatment for patients with stage Ib and IIa Mycosis Fungoides could decrease the cumulative dose of UVA needed to achieve a complete clinical response. The primary objective will therefore be to compare the cumulative dose of UVA required to achieve a CCR in both treatment arms. |
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E.2.2 | Secondary objectives of the trial |
Safety data, overall response rates and the duration of response will also be compared. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histopathologically documented Mycosis Fungoides, clinical stage Ib-IIa confirmed by current or previous diagnostic lesion biopsy -A Karnofsky performance ≥ 60 -Age >18 years -Acceptable organ function defined as follows: -Hemoglobin ≥ 9 g/dl and WBC ≥ 2 x 1000000000/l -Bilirubin ≤ 1.5 times the upper limit of normal for the institution -Creatinine ≤ 2 times the upper limit of normal for the institution -SGOT (AST) and SGPT (ALT) ≤ 2.5 times the upper limit of normal for the institution -Serum calcium between LNN for the institution and ≤ 2.8 mmol/l or 11.5 mg/dl -Fasting serum triglycerides within normal limits for the institution (patients with serum triglycerides that are “normalized” prior to study entry with use of an antilidemic agent may be enrolled) -No evidence of severe cardiac insufficiency, (NYHA grade III-IV) -Women of child bearing potential must have a negative serum pregnancy test (β-HCG) within 7 days prior to randomization -Female patients and male patients with female partners of child bearing potential must agree to practice an effective contraception during the entire period of treatment and for at least 3 months after treatment is discontinued. Female patients with child bearing potential must agree to use a reliable form of contraception. A non-hormonal treatment of contraception is also necessary for women using hormonal contraception methods. Male patients with female sexual partners who are pregnant or potentially pregnant must agree to use condoms during sexual intercourse during the entire period of treatment and for at least 3 months after treatment is discontinued -No other prior or concurrent primary malignant tumor (except adequately treated in situ carcinoma of the cervix or basal or squamous cell skin carcinoma) -No prior systemic combination chemotherapy -TSEB (Total Body Electron Beam) therapy should not have been given less than 6 months before entry into the trial -Topical chemotherapy, photophoresis and interferon should not have been given less than 3 months before entry into the trial -No topical medications (corticosteroids or tar baths), UVB/PUVA phototerapy, superficial radiotherapy, treatment with any other retinoid class drugs or beta-carotene compounds within 1 month before entry into the trial -Absence of any serious intercurrent illness or infection at time of entry into the study that could interfere with planned treatment -Patients must be willing and able to prolonged exposure to the sun. Patients must be willing to accept limited sun exposure on the day receiving PUVA treatment -Absence of intrinsic (lupus) or extrinsic (photosensitive drugs) photosensitivity -Patients must not have participated in any other investigational drug study within 30 days before entry into the trial, or have taken part in any other study of Bexaroten (TargretinTM) capsules -Absence of any psyciological, 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 -Before patient randomization written informed consent must be given according to ICH/GCP and national/local regulations
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E.4 | Principal exclusion criteria |
-Lactating women -Patients who were intolerant or unresponsive to prior PUVA therapy will be excluded -Patients with known contradiction to Bexarotene (TargretinTM) therapy: known hypersensitivity to retinoids, hypervitaminosis A, patients with prior pancreatitis, excessive alcohol consumption, patients taking drugs associated with pancreatic toxicity or known to increase triglyceride concentrations, patients with uncontrolled diabetes mellitus, uncontrolled thyroid disease
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E.5 End points |
E.5.1 | Primary end point(s) |
The cumulative dose of UVA necessary to achieve a complete clinical response in both treatment arms (Arm 1: Liquid Psoralen with UVA irradiation (PUVA). Arm 2: Bexarotene (TargretinTM) and PUVA). |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
PUVA treatment compared to PUVA treatment combined with Bexarotene (TargretinTM) treatment |
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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 | Yes |
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 | Information not present in EudraCT |
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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The trial will end with the last visit of the last subject undergoing this 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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |