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 | 16.1 |
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 progression free survival (PFS) per enhanced Response Evaluation Criteria in Solid Tumours (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 Objective Response Rate (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 overall survival (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. (PART 1 only). (The UK will only participate in part 2 of the study).
(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 pati |
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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 tumour sample. The submitted tumour sample must have tested positive for a loss-of-function p53 mutation as defined in the assay charter (copy enclosed) and the result must be documented by the 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. (The UK will only participate in part 2 of the study)
(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.
(6) Patient has measurable disease based on RECIST 1.1 criteria
(7) Patient is ≥18 years of age on day of signing informed consent.
(8) Patient has a performance status of ≤1 on the ECOG Performance Scale.
(9) Patient must have adequate organ function
(10) Female patient of childbearing potential has a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
(11) Patient has voluntarily agreed to participate by giving written informed consent.
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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 (central nervous system) 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 tumour.
(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.
(5) Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to potent inhibitors / inducers of CYP3A4 or inhibitors of CYP2C8, which cannot be discontinued two weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication.
(6) Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate. Patients with carcinoma in situ of the cervix or basal cell carcinoma of the skin will be permitted enrollment.
(7) Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
(8) Patient is, at the time of signing informed consent, a known regular user(including "recreational use" of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
(9). Patients expecting to reproduce within the projected duration of the study, and
women who are pregnant or breastfeeding.
(10). Patient is known to be Human Immunodeficiency Virus (HIV)-positive.
(11). Patient has known active Hepatitis B or C.
(12). Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible for the study however.
(13). Patient has a clinical history suggestive of Li Fraumeni Syndrome
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficay Outcome measure:
Progression Free Survival (PFS) per Enhanced RECIST 1.1
Primary Safety Outcome measures:
Complete blood counts, coagulation tests, serum chemistry assessment, vital signs, physical examination, and ECOG performance status.
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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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Canada |
Sweden |
Brazil |
Germany |
Hungary |
Israel |
Russian Federation |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 2 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 28 |