E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ovarian Fallopian Tube, or Peritoneal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the ovaries, Fallopian Tube, or peritoneum |
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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 | LLT |
E.1.2 | Classification code | 10033130 |
E.1.2 | Term | Ovarian cancer NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 |
(1) To evaluate the effect of MK-1775 in combination with paclitaxel + carboplatin compared with placebo in combination with paclitaxel + carboplatin on PFS per enhanced RECIST 1.1 in patients with platinum sensitive p53 mutant ovarian cancer. (2) To determine the safety and tolerability of MK-1775 in combination with paclitaxel + carboplatin in patients with platinum sensitive p53 mutant ovarian cancer. |
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E.2.2 | Secondary objectives of the trial |
(1) To evaluate the effect of the combination of paclitaxel + carboplatin in combination with MK-1775 versus paclitaxel + carboplatin alone on ORR in patients with platinum sensitive p53 mutant ovarian cancer. (2) To evaluate the effect of the combination of paclitaxel + carboplatin in combination with MK-1775 versus paclitaxel + carboplatin alone on OS in patients with platinum sensitive p53 mutant ovarian cancer. (3) To determine pharmacodynamic changes induced by MK-1775 combined with paclitaxel + carboplatin in surrogate tissue at the 175 and 125 mg dose, should these dose levels be explored. (4) To assess the pharmacokinetic profile of MK-1775 in combination with paclitaxel + carboplatin in patients with platinum sensitive p53 mutant ovarian cancer. (5) To assess the pharmacokinetic profile of paclitaxel in combination with MK-1775 + carboplatin in patients with platinum sensitive p53 mutant ovarian 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 confirmed non-low grade, non-borderline (low malignant potential) ovarian, fallopian tube, or primary peritoneal cancer that has progressed after paclitaxel / platinum based therapy.
(2) Patients must have platinum sensitive disease. Progression must have occurred 6 months or more after the completion of the most recent platinum based treatment.
(3) Patient is able to provide a baseline tumor sample. The submitted tumor sample must have tested positive for a loss-of-function p53 mutation (as defined in the assay charter) and the result must be documented by a core lab for the study.
(4) Part 1 - Patient may not have received more than two platinum containing treatment regimens for their cancer. Part 2 - Patient may not have received more than three separate regimens of platinum containing treatment for their cancer.
(5) Any biologic therapy or radiation must have been completed four weeks prior to receiving study therapy. With the exception of alopecia, the patient must have recovered to ≤ Grade 1 from adverse events due to previous agents administered. Biologic maintenance therapy (i.e. bevacizumab) is allowable within this six month period. Any biologic maintenance therapy must have been discontinued 28 days prior to the patient starting study therapy. |
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E.4 | Principal exclusion criteria |
(1) 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.
(2) 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.
(3) Patient with a primary central nervous system tumor.
(4) Patient has known hypersensitivity or contraindications to the components of potential study therapy (paclitaxel, carboplatin, MK-1775) or its analogs (i.e. cremophor, mannitol, etc). The MK-1775 Investigator Brochure can be referenced for information regarding study therapy.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) per Enhanced RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS is defined as the time from randomization to progressive disease or death, whichever occurs earlier |
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E.5.2 | Secondary end point(s) |
Progression-free Survival per RECIST 1.1, Objective Response Rate (Enhanced RECIST 1.1 + CA-125), and Overall Survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall Survival is defined as the time from randomization to death due to any cause. Patients without documented death at the time of analysis will be censored at the date last known to be alive. |
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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 | Yes |
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) | 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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Brazil |
Canada |
Germany |
Hungary |
Israel |
Russian Federation |
Sweden |
Taiwan |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 20 |