E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic basal cell carcinoma (BCC) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
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 safety of vismodegib (GDC-0449) in patients with locally advanced or metastatic BCC |
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E.2.2 | Secondary objectives of the trial |
- To assess the overall response rate (according to RECIST Version 1.1) in those patients with measurable disease as permitted by local regulatory requirement.
- To assess other efficacy parameters such as time to response, duration of response, progression-free survival and overall survival.
- To assess patient quality of life.
- To assess the impact of vismodegib treatment on disease symptoms in patients with metastatic BCC who enrolled after approval of the study protocol, version 4.0, using the M.D. Anderson Symptom Inventory.
- To assess the status of the Hedgehog pathway and/or other modifiers of vismodegib activity in tumour tissue obtained from patients with metastatic BCC who have disease progression on vismodegib therapy.
- Adverse event-related pharmacokinetic testing will be performed.
- Post-treatment pharmacokinetic testing will be performed.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written, signed informed consent
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2
4. For patients with metastatic BCC, histologic confirmation of distant BCC metastasis
5. For patients with locally advanced BCC, at least one histologically confirmed lesion 10 mm or more in diameter and written confirmation from a surgical specialist that the tumour is considered inoperable or that surgery is contraindicated. Examples of medical contraindications to surgery include but are not limited to:
• BCC that has recurred in the same location after two or more surgical procedures and curative resection is deemed unlikely
• Anticipated substantial morbidity and/or deformity from surgery (e.g., removal of all or part of a facial structure, such as nose, ear, eyelid, eye; or requirement for limb amputation)
6. For patients with locally advanced BCC, radiotherapy must have been previously administered for locally advanced BCC, unless radiotherapy is contraindicated or inappropriate (e.g., hypersensitivity to radiation due to genetic syndrome such as Gorlin syndrome, limitations because of location of tumour, or cumulative prior radiotherapy dose). For patients whose locally advanced BCC has been irradiated, disease must have progressed after radiation
7. Patients with Gorlin syndrome may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above
8. Patients with measurable and/or non-measurable disease (as defined by RECIST, v1.1) are allowed
9. Adequate organ function, as evidenced by the following laboratory results:
• Haemoglobin > 8.5 g/dL
• Granulocyte count ≥ 1000/μL
• Platelet count ≥ 75,000/μL
• Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) ≤ 3 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 × ULN or within 3 × ULN for patients with documented Gilbert syndrome
10. Women of childbearing 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 24 months after completion of study treatment. Highly-effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (e.g., implants, injectables, combined oral contraception, or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and postovulation methods) and withdrawal are not acceptable methods of contraception.
11. For male patients with female partners of childbearing potential, agreement to use a condom with spermicide, even after vasectomy, during sexual intercourse with female partners while being treated with vismodegib and for 2 months after completion of study treatment.
12. Agreement not to donate blood or blood products during the study and for at least 24 months after discontinuation of vismodegib. Because vismodegib has been detected in seminal fluid, in addition for men, agreement not donate sperm during the study or for at least 2 months after discontinuation of therapy.
13. Life expectancy > 12 weeks
14. Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year. |
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E.4 | Principal exclusion criteria |
1. Inability or unwillingness to swallow capsules
2. Pregnancy or lactation
3. Concurrent non–protocol-specified anti-tumour therapy (e.g., chemotherapy, other targeted therapy, radiation therapy, or photodynamic therapy, including participation in an experimental drug study; note that treatment breaks up to 8 weeks for radiation therapy are allowed)
4. Completion of most recent anti-tumour therapy less than 21 days prior to initiation of treatment
5. Uncontrolled medical illnesses such as infection requiring treatment with intravenous antibiotics
6. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or that renders the patient at high risk from treatment complications
7. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol
8. Patients with one of the following rare hereditary conditions: galactose intolerance, primary hypolactasia, or glucose-galactose malabsorption |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this trial is to assess the safety of vismodegib (GDC-0449) in patients with locally advanced or metastatic BCC. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Until disease progression or unacceptable toxicity (approximately 2 years) |
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E.5.2 | Secondary end point(s) |
- Tumour response rate according to Response Evaluation Criteria in Solid Tumours (RECIST)
- Time to response
- Duration of response
- Progression-free survival
- Overall survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Until disease progression or unacceptable toxicity (approximately 2 years) |
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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 | 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 | Yes |
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) | 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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 137 |
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 |
Albania |
Argentina |
Australia |
Austria |
Belgium |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Canada |
Colombia |
Croatia |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Lithuania |
Mexico |
Netherlands |
New Zealand |
Norway |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
Slovenia |
South Africa |
Spain |
Sweden |
Switzerland |
Turkey |
Ukraine |
United Kingdom |
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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
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The study will end when the last patient on treatment develops progressive disease (as determined by the investigator) or unacceptable toxicity, withdraws consent, or dies; the treating physician deems the patient is no longer benefitting from treatment; or the study is terminated by the Sponsor; or 12 months after the last dose of vismodegib in the last enrolled patient still on study, whichever occurs first. |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |