E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
BRAFV600-mutation positive patients with unresectable locally
advanced or metastatic melanoma |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025650 |
E.1.2 | Term | Malignant melanoma |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027480 |
E.1.2 | Term | Metastatic malignant melanoma |
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 the efficacy of vemurafenib in combination with GDC-0973, compared with vemurafenib and placebo, in previously untreated BRAFV600 mutation-positive patients with unresectable locally advanced or metastatic melanoma, as measured by prolongation of
progression-free survival (PFS), as assessed by the study site investigator. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of vemurafenib in combination with GDC-0973, compared with vemurafenib and placebo, in previously untreated BRAFV600 mutation-positive patients with unresectable locally advanced or metastatic melanoma, as measured by overall survival (OS),
objective response rate (ORR), and duration of response (DOR). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•≥ 18 years of age
•Stage IIIc or Stage IV melanoma harboring BRAF V600 mutation
•BRAF V600 mutation must be confirmed by cobas 4800 BRAF V600 mutation test
•Measurable disease according to RECIST 1.1
•Women of childbearing potential with negative serum pregnancy test prior to randomization
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
•Adequate baseline organ function |
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E.4 | Principal exclusion criteria |
•Any prior use of a BRAF or MEK inhibitor
•Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
•History of another malignancy except subjects who have been disease free for 3 years or have completely resected non-melanoma skin cancer.
•Patients with active CNS lesions (including carcinomatous meningitis) are excluded. However, patients are eligible if:
a)all known CNS lesions have been treated with stereotactic therapy or surgery, AND
b)no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery.
Whole brain radiotherapy is not allowed with the exception of patients who have had definitive resection or stereotactic therapy of all radiologically detectable parenchymal brain lesions.
•Evidence of cardiovascular risk (LVEF < LLN; QTc ≥ 450 msec; blood pressure ≥140/90 mmHg which cannot be controlled by anti-hypertensive therapy)
•History, risk factors for or evidence of neurosensory retinal detachment, retinal vein occlusion or neovascular macular degeneration. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
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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) |
1. Overall Survival
2. Overall Response Rate
3. Duration of Response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. approx. 36 months
2. Time Frame: approx. 16 months
3. Duration of Response |
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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 | Yes |
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 |
tolerability, exploratory exposure-response analysis, health-related quality of life, biomarker 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) | 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 | 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 |
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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
| 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 109 |
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 |
Belgium |
Czech Republic |
France |
Germany |
Hungary |
Iceland |
Italy |
Liechtenstein |
Netherlands |
Norway |
Spain |
Sweden |
United Kingdom |
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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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The study will end when all patients enrolled have been followed until death, withdrawal of consent, lost to follow-up, or the Sponsor decides to end the trial, 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 | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |