E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced/metastatic melanoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic 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 |
Phase 1 - To establish the maximum tolerated dose of GSK1120212 in combination with paclitaxel in the treatment of patients with advanced melanoma.
Phase 2 - To compare the efficacy of GSK1120212 in combination with paclitaxel, compared with paclitaxel alone in the treatment of patients with advanced or metastatic melanoma. |
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E.2.2 | Secondary objectives of the trial |
To further assess the safety and efficacy of GSK1120212 in combination with paclitaxel, compared with paclitaxel alone in the treatment of patients with advanced or metastatic melanoma.
To assess the impact of tumour characteristics on response to paclitaxel therapy with or without GSK1120212. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged ≥ 18 years
2. Able to provide evidence from an accredited laboratory of wt BRAF status for their melanoma, or ascertainment of wt BRAF status from a sample of melanoma provided for mutational analysis in Oxford (phase 2 part only).
3. Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma
4. Measurable disease as defined by RECIST 1.1 (phase 2 part only).
5. ECOG performance score of 0 or 1.
6. Life expectancy of at least 12 weeks.
7. Maximum 2 prior lines of treatment for advanced disease.
8. Adequate cardiac function (NYHA 0-1), and LVEF within normal limits on echocardiogram.
9. The patient is willing to give consent to the main study and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.
10. Adequate haematological, hepatic and renal function.
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E.4 | Principal exclusion criteria |
1. Any systemic anti-cancer therapy (including participation in other clinical trials) within 28 days prior to Day 1.
2. Any radiotherapy within 14 days prior to Day 1.
3. Prior taxane or BRAF or MEK inhibitors for metastatic melanoma.
4. Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade 2.
5. Pregnancy or breastfeeding women. Female patients must have a negative urinary or serum pregnancy test or have evidence of post-menopausal status (defined as absence of menstruation for > 12 months, bilateral oophrectomy or hysterectomy).
6. Grade ≥2 peripheral neuropathy at study entry.
7. Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients)
8. Known severe hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL and ethanol
9. Ocular or mucosal malignant melanoma
10. Another active malignancy within the past three years.
11. Evidence of brain metastases, unless surgically resected/stereotactic radiosurgery treated brain metastasis with no evidence of relapse on cerebral MRI, or treated brain metastasis and stable off treatment, including steroids, for 3 months.
12. Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis.
13. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
14. Inability to swallow tablets, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption.
15. Ocular disease predisposing to central serous retinopathy and/or retinal vein occlusion, including increased intra-ocular pressure, glaucoma, uncontrolled hypertension or uncontrolled diabetes.
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1 component: Maximum tolerated dose of GSK1120212 in combination with paclitaxel Phase 2 component: Progression free survival |
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E.5.2 | Secondary end point(s) |
Overall survival (OS). Objective response rate (ORR) Progression free survival at 6 months (PFS) Adverse events using CTCAE v4.0 Vital signs and weight Biochemistry, haematology and urinalysis Physical examination ECG |
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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 | 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 | 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) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | 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 ‘end of trial’ is defined as the last visit of the last patient undergoing the trial, or 9 months after the last patient is randomised, whichever is the sooner. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 29 |