E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Second-line treatment of KRAS mutant-type metastatic colorectal cancer. |
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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 |
The primary objective is to estimate the treatment effect on progression-free survival (PFS) of AMG 655 plus FOLFIRI or AMG 479 plus FOLFIRI relative to FOLFIRI alone when administered as a second-line treatment for subjects with metastatic colorectal cancer (mCRC) whose tumors express mutant-type Kirsten rat sarcoma virus oncogene homolog (KRAS). |
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E.2.2 | Secondary objectives of the trial |
To estimate treatment effect on overall survival (OS), Objective Response Rate (ORR =complete response [CR] + partial response [PR]), rates of disease control (= complete [CR] + partial [PR] + stable disease [SD]), duration of response (DOR), and time to response (TTR) To evaluate the incidence of adverse events and significant laboratory abnormalities and the incidence of anti-AMG 655 or anti-AMG 479 antibody formation To evaluate treatment effect on patient-reported outcomes (PRO) using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire-core questionnaire (EORTC QLQ-C30) and the FACT/NCCN-Colorectal Symptom Index (FCSI) To evaluate pharmacokinetics (PK) of AMG 655, AMG 479 and FOLFIRI components (irinotecan and 5-FU), and estimate the impact of administration of AMG 655 and AMG 479 on the PK of FOLFIRI components (irinotecan and 5-FU) To correlate treatment outcomes with tumor tissue analysis of somatic gene mutations. |
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E.2.3 | Trial contains a sub-study | Yes |
E.3 | Principal inclusion criteria |
Men or women 18 years of age or older at the time the written informed consent is obtained Histologically confirmed adenocarcinoma of the colon or rectum in patients with metastatic disease Mutant-type KRAS tumor status confirmed by central laboratory assessment of formalin-fixed paraffin-embedded tumor tissue from the primary tumor or metastasis One and only one prior anti-cancer therapy regimen for metastatic disease consisting of the combination of a fluoropyrimidine and oxaliplatin-based chemotherapy with or without anti- VEGF therapy. Prior adjuvant or neo-adjuvant chemotherapy used prior to the onset of metastatic disease is permitted. Documented disease progression while receiving or ≤ 6 months after the last dose of prior first-line fluoropyrimidine and oxaliplatin-based chemotherapy with or without anti-VEGF therapy for metastatic disease Measurable or non-measurable disease according to modified RECIST criteria. Lesions must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to randomization. All sites of disease must be evaluated ≤ 28 days prior to randomization. ECOG performance status of 0 or 1 Subjects with diabetes (Type 1 or 2) must be controlled with glycosylated hemoglobin (HgbA1c) ≤ 8% and fasting blood glucose level ≤160 mg/dL; diabetic subjects who have recently had their glycemic control regimens adjusted and have documented fasting blood glucose concentrations ≤ 160 mg/dL may be considered, regardless of HgbA1c value, if per investigator discretion they are considered to have adequate glycemic function Adequate hematology, renal, hepatic, and coagulation function |
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E.4 | Principal exclusion criteria |
History or known presence of central nervous system (CNS) metastases History of other malignancy, except: − Malignancy treated with curative intent and with no known active disease present for ≥ 3 years prior to randomization and felt to be at low risk for recurrence by the treating physician − Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease − Adequately treated cervical carcinoma in situ without evidence of disease − Prostatic intraepithelial neoplasia without evidence of prostate cancer Prior irinotecan-based chemotherapy for advanced/metastatic disease Prior death receptor agonists (such as rhApo2/TRAIL [AMG 951]), apomab, mapatumumab, lexatumumab, CS-1008), or other systemic IGF-1R antagonists (such as CP-751, 951, MK0646, IMC-A12) in any setting Systemic chemotherapy, hormonal therapy, immunotherapy or experimental or approved anticancer proteins/antibodies therapy ≤ 21 days before randomization Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities. Unresolved toxicities from prior anti-cancer therapy that, in the opinion of the investigator, excludes subject from participation Significant cardiovascular risk Pulmonary embolism, deep vein thrombosis, or other venous/arterial thromboembolic events ≤ 12 months before randomization Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as ≥ CTCAE grade 2, |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) |
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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
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the end of the study will occur when all subjects have died or completed the long -term follow-up period (maximum 36 months from the date that the last subject has been randomized), whichever is earlier. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 |