E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Carcinomas of Unknown Primary origin (CUP) |
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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 |
Translational: To select the molecular classifier with the highest diagnostic accuracy
Clinical Trial: To estimate the response rate from the ECX regimen
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E.2.2 | Secondary objectives of the trial |
Clinical Trial 1. Progression-free survival 2. Overall survival 3. Cost-utility comparison of diagnostic molecular classifiers with average clinical diagnostic work-up 4. Correlation of molecular profiles with patient outcome 5. Identification of potential prognostic metabonomic signatures to efficacy & toxicity profiles
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
INCLUSION - TRANSLATIONAL PART 1. Uncertain or unknown primary site of origin of malignancy 2. Histologically confirmed carcinomas (adenocarcinomas, SCC & undifferentiated are all acceptable) from tru-cut biopsy and/ or operative procedure - lymphomas, sarcomas, germ-cell tumours are not intended to be either part of this trial, if uncertain or equivocal they can be discussed with the TMG - Cytologically confirmed carcinomas, in which a primary cannot be found following appropriate investigations (see below), can be offered the study only if either a subsequent tru-cut biopsy and/or operative procedure is to be performed at some stage of the patients investigations or surgical treatment (such as debulking or bypass surgery). Written informed consent is required for both parts separately.
INCLUSION - CLINICAL TRIAL 1. Histologically or cytologically confirmed carcinomas, in which a primary cannot be conclusively identified following appropriate investigations and discussion in the appropriate MDM (see 4.1 above). - Lymphomas, sarcomas and germ-cell tumours are not intended to be part of this trial, if uncertain or equivocal they can be discussed with the TMG - Cytologically confirmed carcinomas, in which a primary cannot be found following appropriate investigations (see 4.3 below), can be offered both parts of the study only if either a subsequent tru-cut biopsy and/or operative procedure is to be performed at some stage of the patient’s investigations or surgical treatment (such as debulking or bypass surgery). Written informed consent is required for both parts separately. - If only cytological confirmation from a FNA is possible, only the second part of the study can be considered. 2. Inoperable metastatic carcinoma with at least unidimensional measurable disease. 3. Age > 18 years 4. Performance status < 2 5. Life expectancy >12 weeks 6. Adequate haematological function: absolute neutrophil count > 2.0 x 109/l, white cell count > 3.0 x 109/l, platelets > 100 x 109/l 7. Adequate renal function: serum creatinine < 120m/l and creatinine clearance > 50 ml/min 8. Adequate hepatic function: bilirubin within 2x normal range, AST or ALT > 5 times the upper limit of normal 9. Written informed consent
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E.4 | Principal exclusion criteria |
EXCLUSION - TRANSLATIONAL 1. Significant intercurrent medical or psychiatric illness which in the opinion of the investigator would compromise the patient's ability to give informed consent 2. Non-carcinoma histology (lymphomas, sarcomas and germ-cell tumours are not intended to be part of this trial; if equivocal discuss with TMG)
EXCLUSION - CLINICAL TRIAL 1. Previous chemotherapy 2. Co-existent second malignancy or history of prior malignancy within 5 years, except for adequately treated basal cell carcinoma and non-invasive carcinoma of the cervix. If history of prior malignancy within 10 years, the previous histology should be compared and available for central review. 3. Pregnant or lactating women. Women of child bearing potential not prepared to use effective contraception 4. Significant intercurrent medical or psychiatric illness which in the opinion of the investigator would compromise the patient's ability to give informed consent or tolerate the therapy 5. Uncontrolled angina pectoris, heart failure, clinically significant uncontrolled cardiac arrhythmias, or any patient with a clinically significant abnormal ECG or cardiac history having a LVEF of lower limit of normal range for institution as determined by MUGA scan or echocardiogram. 6. The presence of proven cerebral metastases 7. Any chemotherapy, hormonal or immunotherapy or other investigational drug within the preceding 4 weeks (steroids are permissible). 8. Previous radiotherapy is allowed but not to sites of assessable disease. No chemotherapy is to be given until resolution of all acute radiotherapy effects or a minimum of 6 weeks has elapsed since end of radiotherapy. Radiosensitisation with chemotherapy during radiotherapy is not allowed.
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E.5 End points |
E.5.1 | Primary end point(s) |
For the translational part the primary objective is to select the molecular classifier with the highest diagnostic accuracy.
For the clinical trial part the primary objective is to estimate the response rate with ECX.
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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 | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |