E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 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 |
To investigate the effect of bevacizumab and tocotrienol based on the level of methylated circulating tumor specific HOXA9 DNA (HOXA9 meth-ctDNA) after the first treatment cycle assessed by progression free survival |
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E.2.2 | Secondary objectives of the trial |
• To investigate overall survival
• To investigate the response rate
• To investigate potential toxicity to treatment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed epithelial ovarian cancer, primary fallopian or primary peritoneal cancer.
• Platinum resistant epithelial ovarian cancer treated with at least two different previous chemotherapeutic regimens
• Progression on previous treatment. Previous treatment with bevacizumab is allowed.
• Measurable disease by the RECIST 1.1 criteria or evaluable by the GCIG CA-125 criteria.
• Age ≥ 18 years.
• Performance status 0-2.
• Adequate bone marrow function, liver function, and renal function (within 7 days prior to inclusion):
o WBC ≥ 3.0 x 10^9/l or neutrophils (ANC) ≥ 1.5 x 10^9/l
o Platelet count ≥ 100 x 10^9/l
o Hemoglobin ≥ 6 mmol/l
o Serum bilirubin < 2.0 x ULN
o Serum transaminase ≤ 2.5 x ULN
o Serum creatinine ≤ 1.5 ULN
• Urine dipstick for protein < 2+. If the dipstick shows protein ≥ 2+, 24 hour urine testing must be performed and show protein contents < 1 g.
• Written informed consent |
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E.4 | Principal exclusion criteria |
• Other malignant diseases within 3 years prior to inclusion in the study, except curatively treated basal cell or squamous cell carcinoma of the skin.
• Other experimental therapy or participation in another clinical trial within 28 days prior to treatment initiation.
• Intestinal infiltration or infiltration in major blood vessels at the discretion of the treating physician.
• Underlying medical disease not adequately treated (diabetes, cardiac disease).
• Uncontrolled hypertension (BP > 150/100 despite antihypertensive treatment).
• Surgery including open biopsy, within 4 weeks prior to first dose of bevacizumab.
• Cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within 6 months before start of treatment.
• Clinical significant cardiovascular disease, including:
o Myocardial infarction or unstable angina within 6 months before start of treatment
o New York Heart Association (NYHA) class ≥ 2
o Poorly controlled cardiac arrhythmia despite medication
o Peripheral vascular disease grade ≥ 3
• Allergy to active substance or any of the auxiliary agents
• Bleeding tumor
• Pregnant or breast-feeding patients. For fertile women a negative pregnancy test at screening is mandatory.
• Fertile patients not willing to use effective methods of contraception during treatment and for 6 months after the end of treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival after the first cycle of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 9 weeks until progression |
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E.5.2 | Secondary end point(s) |
1 Overall survival
2 Response rate
3 Safety
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. One year after enrolment of the last patient
2. Every 9 weeks until progression
3. Every three weeks until progression |
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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 | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | 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 | No |
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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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 | 0 |