E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Phase I: Determination of the maximum tolerated dose (MTD) or maximum feasible dose (MFD) and the recommended dose for the Phase IIa part (RP2D). Phase IIa: Determination of the preliminary efficacy of intrahepatic artery injection of TG6002 in combination with 5-FC. |
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E.2.2 | Secondary objectives of the trial |
Phase I: 1. Safety 2. Efficacy 3. TG6002 in urine, saliva and faeces 4. TG6002 in blood 5. 5-FC, 5-FU and FBAL in serum 6. TG6002 in tumor 7. 5-FC, 5-FU and FBAL in tumor
Phase IIa: 1. Safety 2. Efficacy with other endpoints 3. TG6002 in blood 4. 5-FC, 5-FU and FBAL in serum 5. TG6002 in tumor 6. 5-FC, 5-FU and FBAL in tumor |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histological or cytological diagnosis of colorectal cancer. 2. Unresectable metastatic colorectal cancer with at least one measurable liver metastasis. 3. At least one liver metastasis amenable to biopsy. 4. Patients previously exposed to fluoropyrimidine-based chemotherapy. 5. (Phase I) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy, or patients on or entering a period of clinical observation without treatment. 6. (Phase IIa) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy. |
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E.4 | Principal exclusion criteria |
1. Predominant extrahepatic disease. 2. Symptomatic brain metastases or meningeal tumors. 3. Documented occlusion of the hepatic artery or main portal vein. 4. Reverse portal vein flow on ultrasound sonography. 5. Any contraindication to intrahepatic artery infusion procedure including portosystemic shunt, and artery occlusive disease (ceoliac trunk and/or superior mesenteric artery), if it may inhibit catheterization of the hepatic artery. 6. History of severe exfoliative skin condition (e.g. eczema or atopic dermatitis) requiring systemic therapy for more than 4 weeks within 2 years prior to TG6002 treatment initiation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I: Dose-limiting toxicities, adverse events, serious adverse events, change in standard laboratory parameters and vital signs. Phase IIa: Disease control rate (DCR). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I: Days 1, 2, 4, 8, 15 and 29. Phase IIa: Ten (10) weeks from the first intrahepatic artery TG6002 injection. |
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E.5.2 | Secondary end point(s) |
Phase I: 1. Adverse events, serious adverse events, change in standard laboratory parameters and vital signs. 2. DCR. 3. Quantification of viral particles in urine, saliva and faeces. 4. Quantification of viral particles in blood. 5. Concentration of 5-FC, 5-FU and FBAL in serum. 6. Quantification of viral particles in tumor. 7. Concentration of 5-FC, 5-FU and FBAL in tumor.
Phase IIa: 1. Adverse events, serious adverse events, change in standard laboratory parameters and vital signs. 2. Overall response rate (ORR), duration of response (DoR), progression-free survival (PFS), sum of longest diameters (SLD) of target lesions and overall survival (OS). 3. Quantification of viral particles in blood. 4. Concentration of 5-FC, 5-FU and FBAL in serum. 5. Quantification of viral particles in tumor. 6. Concentration of 5-FC, 5-FU and FBAL in tumor.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase I: 1. Days 1, 2, 4, 8, 15, 29, 43, 44, 46, 50, 57, 71, 85 and every 8 weeks thereafter. 2. Ten (10) weeks from the first intrahepatic artery TG6002 injection. 3. Days 2 and 8. 4. Days 1, 2, 4 or 8, 43 and 44. 5. Days 8 and 50. 6. Day 4 or 8. 7. Day 4 or 8.
Phase IIa: 1. Days 1, 2, 4, 8, 15, 29, 43, 44, 46, 50, 57, 71, 85 and every 8 weeks thereafter. 2. Days 29 and 71 and every 8 weeks thereafter. 3. Days 1, 2, 4 or 8, 43 and 44. 4. Days 8 and 50. 5. Day 4 or 8. 6. Day 4 or 8.
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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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 1 |