E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Endometrial and Cervical Cancer |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In patients with cancer of the womb (endometrial and cervical cancer), the detection of tumour in adjacent lymph glands (nodes) is very important for optimal treatment planning. Currently the standard method used to identify cancerous spread is to surgically remove and examine the nodes under the micrscope in order to identify tumour spread in the nodes. A technique that does not require surgical intervention would be highly desirable. Standard imaging on MRI or CT, in which size criteria are used to identify whether a node is malignant, is inaccurate.
This study will evaluate three new imaging techniques that may be used to identify malignant nodes preoperatively: (1) Diffusion Weighted MRI, (2) FDG-PET/CT and (3) FEC-PET/CT. The principal objective is to compare the diagnostic performance of each test (detection and false-positive rates) with that of the standard method (size criteria) with histology as the reference standard.
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E.2.2 | Secondary objectives of the trial |
1) To compare the diagnostic accuracy of FDG-PET/CT, DW-MRI and FEC-PET/CT to each other in the preoperative diagnosis of metastases in patients with endometrial and cervical cancer. 2) To determine whether one imaging modality performs better than the other in particular sub-groups, such as, particular histological sub-groups. 3) To determine whether FEC-PET/CT uptake reflects changes in histologic findings.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Females older than 18 years; (no upper limit). 2. Patients with histologically confirmed cancer of the cervix or endometrium. a. In patient with cervix cancer, there must be confirmation of invasive disease; FIGO stage 1B1 or higher FIGO stage demonstrated clinically and/or on MRI. In patients with advanced disease being considered for chemoradiotherapy treatment, patients may be considered for entry if nodal lymphadenectomy is being used to inform radiotherapy planning; b. In patients with endometrial cancer, a) stage 1A with myometrial invasion or any higher stage and grade 3 histology with lymphovascular space invasion, b) stage 1A with myometrial invasion or any other higher stage and mixed mullerian, serous papillary or clear cell sub-types. c. Stage II disease or above and any histology grade The MDT decision may be based on the combination of tumour characteristics on histology, clinical and imaging findings. 3. No contra-indication to FDG-PET/CT, FEC-PET/CT or MRI. 4. Fit for surgical lymphadenectomy, as determined by the local MDT. The patient should also be considered fit for extended field radiotherapy in cases where lymphadenectomy is being undertaken to inform radiotherapy planning. 5. Able and willing to give written informed consent and to comply with the study protocol procedures |
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E.4 | Principal exclusion criteria |
1. Known contra-indication to MRI or PET/CT scan. 2. Known allergy to FDG or FEC. 3. Not considered fit for lymphadenectomy (open or laparoscopic) or, where appropriate, radiotherapy, as determined by the local MDT. 4. If the patient is pregnant or breast-feeding. 5. Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after the last PET/CT scan. 5. Note: subjects are not considered of childbearing potential if they are surgically sterile (they have undergone bilateral tubal ligation or bilateral oophorectomy) or they are postmenopausal 6. Females of childbearing potential must have a negative pregnancy test prior to being registered for the study. 7. Medical or psychiatric illness, which makes the patient unsuitable or unable to give informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
Our primary outcome measure is the detection rate (DR) and false positive rate (FPR) for each of the diagnostic modalities. DR is the proportion of women with positive histology who are classified as positive by the diagnostic test. DR is also known as sensitivity.
False-positive rate (FPR) is the proportion of women with negative histology classified as positive by the diagnostic test. FPR is also known as 1 minus specificity.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
These endpoints will be evaluated at the end of the study, once all patients have completed the study |
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E.5.2 | Secondary end point(s) |
The following are secondary endpoints for the MAPPING study:
To compare the diagnostic performance of FDG-PET/CT, FEC-PET/CT and DW-MRI to each other in the preoperative diagnosis of metastases in patients with endometrial and cervical cancer using histology as the reference standard
To determine whether one imaging modality performs better than the other in particular sub-groups, e.g., cervical versus endometrial cancer, different histological/biological sub-types or in advanced stage disease.
To determine whether these leading edge imaging technologies can improve the accuracy of delineation of tumour in planning 3-dimensional radiotherapy target volumes.
To determine whether the uptake of FDG, FEC and diffusion characteristics correlate with histopathological markers. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These endpoints will be evaluated at the end of the study, once all patients have completed the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
staging MRI Scans and histopathology (perfored as per standard of care in this group of patients) |
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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
| 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 | 8 |
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
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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 | 4 |
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 | 4 |
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 |