E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Colorectal Adenocarcinoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
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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 compare overall survival (OS) with TroVax vs. Placebo in patients with metastatic colorectal cancer receiving chemo-based therapy in first line treatment. |
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E.2.2 | Secondary objectives of the trial |
- To compare PFS between TroVax vs. Placebo arms. - To compare Objective Response rate (ORR) between TroVax vs. Placebo arms. - To assess the safety and tolerability of TroVax and Placebo arms.
+ Exploratory: - To assess the immunologic response (5T4 and MVA antibody titers and T-cells) in a subgroup of this patient population (in selected centers). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Exploratory endpoint of the main protocol: To assess the immunologic response (5T4 and MVA antibody titers and T-cells) in a subgroup of this patient population (in selected centers). |
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E.3 | Principal inclusion criteria |
- Patients with histology/cytology confirmed colorectal adenocarcinoma - Metastatic colorectal cancer - No prior palliative chemotherapy - Patient's informed consent obtained, signed and dated. |
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E.4 | Principal exclusion criteria |
* Related to study methodology - Age < 18 years old - ECOG performance status > 2 - (Neo)Adjuvant chemotherapy if<6 months between end of (neo)adjuvant chemotherapy and relapse - Less than 6 weeks elapsed from prior radiotherapy and less than 3 weeks from surgery to time to randomization. - Treatment with an investigational agent within 4 weeks (6 weeks for immuno-therapy) of study enrollment. - Patients with resectable liver or lung metastasis (study treatment should not be administered with neo-adjuvant intent in case of resectable liver or lung metastases or with adjuvant intent after surgery of liver or lung metastases). - Known brain metastasis or leptomeningeal disease - History of other neoplasms. Patients with a prior history of either non-metastatic nonmelanoma skin cancers, or carcinoma in situ of the cervix, or other cancer cured by surgery, or small field radiation or chemotherapy ≥ 5 years prior to randomization are eligible. - Life expectancy < 3 months
*Related to chemo-based therapy (biological functions within 8 days before first cycle: repeat in-range results within the screening period may replace previous out of range results in applying these exclusion criteria) - Absolute neutrophil count (ANC) < 1.5 x 10e9/L, hemoglobin < 8.5 g/dL, platelet < 75 x 10e9/L. - Bilirubin ≥ 1.5 x ULN, AST/ALT or akaline phosphatase (AP) ≥ 3.0 x ULN, or in case of liver involvement AST/ALT or AP ≥ 5 x ULN. - Creatinine > 1.0 x ULN, except in case of creatinine > 1.0 x ULN and ≤ 1.5 x ULN if calculated creatinine clearance ≥ 60 mL/min. - Any other active illness such as uncontrolled cardiac disease or hypertension, uncontrolled diabetes that would preclude safe administration of study therapy at the time of randomization. Any of the following events within 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/ peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant arrhythmias (grade 3-4).
* Related to TroVax - Lymphocytes < 1 x 10e9/L - Serious infection within 28 days prior to randomization - History of hypersensitivity to vaccinia vaccination - Known hypersensitivity to egg protein or neomycin - Known positive test to HIV or any congenital or acquired immune deficiency, or active and/or requiring treatment hepatitis B or C. - Active eczema with lesions on the skin - Prior history of organ transplantation.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is overall survival (OS) defined as the time interval from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time will be censored at the earlier of the last date the patient is known to be alive and the study cut-off date.study cut-off date. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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The termination of the study and the final cut-off date for survival will be the date when it is determined that approximately 854 deaths have occurred. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |