E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with multiple basal cell carcinomas (BCCs). |
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E.1.1.1 | Medical condition in easily understood language |
Adult patients with multiple basal cell carcinomas. |
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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 | 10004146 |
E.1.2 | Term | Basal cell carcinoma |
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 assess the relative reduction from baseline (%) in the number of clinically evident BCCs at a defined time point in two different vismodegib regiments. |
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E.2.2 | Secondary objectives of the trial |
- drop-out rate
- relative reduction from baseline in total size of BCCs
- recurrence rate
- safety
- patient reported outcomes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written, signed informed consent, including consent for photographs of target lesions (required) and non-target lesions (optional)
- Age ≥ 18 years
- Have multiple BCCs, including patients with Gorlin syndrome, with significant burden of skin disease as manifested by at least 6 clinically evident BCCs at the time of randomization, at least three of which measure 5 mm or more in diameter (target lesions)
- Histopathologic confirmation that at least one of the three target lesions is BCC before randomization (2 mm punch biopsy)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Adequate hematopoietic capacity, hepatic and renal function
- For women of childbearing potential a negative pregnancy test within 7 days prior to commencement of dosing is required
- Women of child-bearing potential must use two methods of acceptable contraception including one highly effective method and a barrier method, as directed by their physician, during treatment and for at least 7 months after completion of study treatment.
- For male patients with female partners of childbearing potential, agreement to use a condom, even after a vasectomy, during sexual intercourse with female partners while being treated with vismodegib/placebo, and for 2 months after completion of study treatment
- Agreement not to donate blood or blood products during the study and for at least 7 months after completion of study treatment
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E.4 | Principal exclusion criteria |
- Inability or unwillingness to swallow capsules and to comply with study procedures
- Pregnancy or breastfeeding
- Any metastatic BCC
- Locally advanced BCC lesion that is considered to be inoperable or to have a medical contraindication to surgery in the opinion of a Mohs surgeon, dermatologic surgeon, head and neck surgeon, surgical oncologist, or plastic surgeon.
- Recent (i.e., within the past 28 days prior to randomization) or current participation in another experimental drug study
- Uncontrolled medical illness, including advanced malignancies, at the discretion of the Investigator
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications
- Any medical or psychological illness or condition preventing adequate consent or ability to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative reduction from baseline (%) in the number of clinically evident BCCs at a defined time point in two different vismodegib regiments |
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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) |
Drop-out rate, relative reduction from baseline in total size of BCCs, recurrence rate, safety, patient reported outcomes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment Phase (Week 9, 17, 25, 33, 41, 49, 57 and 65), Week 73, 85, 97 and 125 |
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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 | 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 | 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 |
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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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
two treatment regimens (alternance of vismodegib and placebo) |
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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
| Information not present in EudraCT |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Austria |
Brazil |
Canada |
France |
Germany |
Italy |
Mexico |
Netherlands |
Russian Federation |
Spain |
Switzerland |
United Kingdom |
United States |
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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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LPLV (the end of study visit will be performed after 52 weeks of follow-up after completion of the study treatment) |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |