| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Progressive, advanced ovarian cancer | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10033128 | | E.1.2 | Term | Ovarian cancer | |
| 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 estimate the response rate of the combination of decitabine and carboplatin compared to carboplatin alone in patients with progressive advanced ovarian cancer who have previously responded to platinum based chemotherapy and who have methylated hMLH1 DNA in plasma. | |
| E.2.2 | Secondary objectives of the trial | 1) To estimate the response rate of the combination of decitabine and carboplatin compared to carboplatin alone in all patients regardless of methylation status.
2) To determine progression free survival and overall survival in patients with this drug combination, who have methylated hMLH1 DNA in plasma and in all patients.
3) To examine the safety and tolerability of this drug combination.
4) To determine the feasilbility of combining decitabine with carboplatin.
5) To determine the incidence of hypersensitivity reactions to carboplatin.
6) To study the relationship between peak plasma levels of decitabine and global CpG island specific methylation.
7) To study the relationship between global and gene specific methylation in PMN cells and response. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1) Histologically or cytologically proven progressive, epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer. (Progression is defined by GCIG guidelines (RECIST criteria and/or CA-125 criteria)).
2) Maximum of one prior line of treatment. This must have been a platinum containing regimen.
3) A clinical response by RECIST criteria and/or CA-125 criteria to the one prior platinum containing regimen with relapse of disease at least 6 months but no greater than 12 months after completion of treatment.
Patients who have progression of disease by CA-125 criteria alone within 6 months of the end of treatment will be eligible provided study treatment does not commence within 6 months of previous treatment.
Patients who have progression of disease as defined by GCIG guidelines within 12 months after completion of previous treatment will be eligible provided that treatment on study commences within 14 months.
4) Measurable disease by RECIST criteria and/or by GCIG CA-125 criteria
• Measurable Disease. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques (physical examination, CT, X-ray, MRI) or as > 10 mm with spiral CT scan.
• Patients can be evaluated according to CA-125 if they have a pre-treatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment. Patients are not evaluable if they have received mouse antibodies or if there has been medical and/or surgical interference with their peritoneum or pleura during the previous 28 days. E.g. paracentesis
Patient with ascites requiring therapeutic drainage are eligible only if they have disease measurable by RECIST criteria. Ascitic sampling for pharmacodynamic analysis will only be taken in patients with disease measurable by RECIST criteria.
Radiological measurements to assess response must be performed within 4 weeks prior to the patient going on study and at least 4 weeks after the last anti-cancer therapy.
Clinical measurements must be done within one week of the patient going on study.
5) WHO performance status of 0 to 2
6) Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient goes on study.
Lab Test Value Required
Haemoglobin (Hb) ≥10.0 g/dl
WBC ≥3.0 x 10(9)/L
Neutrophils ≥1.5 x 10(9)/L
Platelets (Plts) ≥100 x 10(9)/L
Plasma bilirubin ≤30µmol/L
ALT and/ or AST (If both are measured then both must satisfy these limits) ≤ 2.5 x upper limit of normal (ULN) unless due to tumour in which case up to 5 x ULN
EDTA/DTPA clearance (radioisotope method) ≥50ml/min
7) 18 years or over
8) Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up
| |
| E.4 | Principal exclusion criteria | 1) Radiotherapy, endocrine therapy, immunotherapy or chemotherapy during the previous four weeks before treatment.
2) Toxic manifestations of previous treatments. Exceptions to this are alopecia and grade 1 neuropathy and certain Grade 1 toxicities which in the opinion of the Investigator and Cancer Research UK should not exclude the patient.
3) Patients must not be intolerant of carboplatin where intolerance is defined as: with a dose of at least AUC 5:
• Myelotoxicity causing dose delay on more than two occasions
• Grade III or IV hypersensitivity reaction
• Hospitalisation for febrile neutropenia (>38ºC)
• Requirement for platelet transfusion
4) Patients who have received more than 6 cycles of carboplatin.
5) Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use appropriate medically approved contraception for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible.
6) Major thoracic and/or abdominal surgery in the preceding four weeks from which the patient has not recovered.
7) At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
8) Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
9) Current malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.
10) Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Any response (partial or complete) in any of the patients as determined by RECIST criteria or CA-125 levels in patients without measurable disease at baseline. | |
| 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 | Yes |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| 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) | 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 | 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 | 9 |
| 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 | Information not present in EudraCT |
| 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 | | last visit of the last patient undergoing the trial | |
| 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 |
| 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 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
