E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy resistant ovarian cancer with progressive disease. |
|
E.1.1.1 | Medical condition in easily understood language |
Ovarian cancer with no effect of chemotherapy |
|
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 | 17.1 |
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 |
|
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 tocotrienol as a nutritional supplement in combination with bevacizumab in patients with advanced ovarian cancer |
|
E.2.2 | Secondary objectives of the trial |
• To investigate quality of life during treatment
• To investigate the potential toxicity of the treatment
• To investigate progression free and overall survival
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed epithelial, primary fallopian or primary peritoneal cancer.
• Prior treatment with at least two different cytostatic regimens including platinum.
• Progression on previous treatment.
• Measurable disease by RECIST 1.1 or evaluable by GCIG CA-125 criteria.
• Age ≥ 18 years.
• Performance stage 0-2.
• Adequate bone marrow function, liver function, and renal function (within 7 days prior to inclusion):
- WBC ≥ 3.0 * 109/l or neutrophils (ANC) ≥ 1.5 * 10^9/l
- Platelet count ≥ 100 * 10^9/l
- Hemoglobin ≥ 6 mmol/l
- Serum bilirubin < 2.0 * ULN
- Serum transaminase ≤ 2.5 * ULN
- Serum creatinine ≤ 1.5 ULN
• Urine dipstick for protein <2+. If the dipstick shows protein ≥2+ 24 hour urine testing must be made with protein contents < 1 g.
• Written informed consent. |
|
E.4 | Principal exclusion criteria |
• Other malignant diseases within 5 years prior to inclusion in the study, except curatively treated basal cell or squamous cell carcinoma of the skin and other types of cancer with minimal risk of recurrence.
• Other experimental therapy or participation in another clinical trial within 28 days prior to treatment initiation.
• Underlying medical disease not adequately treated (diabetes, cardiac disease).
• Uncontrolled hypertension (BT >150/100 despite antihypertensive treatment).
• Surgery, incl. open biopsy, within 4 weeks prior to first dose of bevacizumab.
• Non-healing wounds or fractures.
• Cerebral vascular attack, transient ischemic attack or subarachnoidal hemorhage within 6 months before start of treatment.
• Clinically significant cardiovascular disease, including:
- Myocardial infarction or unstable angina within 6 months before start of treatment
- New York heart Association (NYHA) class ≥ 2
- Poorly controlled cardiac arrhythmia despite medication
- Periferal vascular disease grade ≥ 3
• Allergy to the 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Fraction of patients without progression after six months of treatment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after first treatment day |
|
E.5.2 | Secondary end point(s) |
1 Quality of life
2 Safety
3 Progression free survival
4 Overall survival |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1+3 = Every 9 weeks
2 = Every 3 weeks |
|
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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
|
LVLS anticipated to be 30 June 2015 |
|
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 | |