E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced, metastatic, and recurrent carcinoma of the uterine cervix |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
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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 |
Part 1 : (1) To determine the safety and tolerability of MK-1775 in combination with topotecan and cisplatin in patients with advanced, metastatic, and recurrent cervical cancer. (2) To establish a Phase II / Maximum Tolerated Dose for MK 1775 in combination with topotecan + cisplatin. (3) To determine the preliminary efficacy of MK-1775 in combination with topotecan and cisplatin in patients with advanced, metastatic, and recurrent cervical cancer. Part 2 : (1) To evaluate the effect of the combination of topotecan/cisplatin + MK-1775 versus topotecan/cisplatin alone on PFS in patients with advanced, metastatic, and recurrent cervical cancer. (2) To determine the safety and tolerability of MK-1775 in combination with topotecan and cisplatin in patients with advanced, metastatic, and recurrent cervical cancer. |
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E.2.2 | Secondary objectives of the trial |
Part 1 : (1) To assess the pharmacokinetic profile of MK-1775 in combination with topotecan and cisplatin in patients with advanced, metastatic, and recurrent cervical cancer. (2) To determine pharmacodynamic changes in skin induced by MK-1775 in combination with topotecan and cisplatin in patients with advanced, metastatic, or recurrent cervical cancer. Part 2: (1) To evaluate the effect of the combination of topotecan/cisplatin + MK-1775 versus topotecan/cisplatin alone on OResponse Rate in patients with advanced, metastatic, and recurrent cervical cancer. (2) To evaluate the effect of the combination of topotecan/cisplatin + MK-1775 versus topotecan/cisplatin alone on Overall Survival in patients with advanced, metastatic, and recurrent cervical cancer. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient must have a histologically or cytologically confirmed advanced, metastatic, and recurrent carcinoma of the uterine cervix (Stage II – IVb). 2. Patient must have received platinum in combination with radiation as initial or adjuvant treatment for their cervical cancer. 3. Patient may not have received any other treatment for their cancer following the chemo-radiation or targeted therapy with the exception of non-cytotoxic targeted therapy. 4. Recurrence must have occurred at least 6 months post platinum-based chemo-radiotherapy.
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E.4 | Principal exclusion criteria |
1. Patient has had chemotherapy, radiotherapy, or biological therapy within 6 months prior to entering the study or who has not recovered from adverse events due to agents administered more than 6 months earlier. 2. Patient is currently participating or has participated in a study with an investigational compound or device within 28 days of receiving first dose of study medication. 3. Patients with active CNS metastases and/or carcinomatous meningitis are excluded. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids for at least 2 weeks. 4. Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be metabolized by CYP3A4, or to inhibit or induce CYP3A4, which cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication.
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of safety, efficacy, Progression Free Survival, pharmacokinetics, and the pharmacokinetic / pharmacodynamic relationship of MK1775 in combination with cisplatin/topotecan. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Dose finding in combination with cisplatin/topotecan. |
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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 | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
part 1 is open, part 2 is randomised, double blind and has parallel groups |
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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
| 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.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Information not present in EudraCT |
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 |
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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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Currently, the end of trial for this study is not fixed. Patients will continue treatment until progression of disease or intolerable side-effects. After discontinuation, patients in part 2 will continue in a long-term follow-up phase until death or lost to follow-up. For efficacy evaluation, part 2 of the study will be event driven with a target of 74 PFS events. |
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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 | 0 |
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 | 0 |