E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
wild-type KRAS 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 |
To evaluate the efficacy as assessed by the overall objective response rate (ORR) of AMG 102 (tolerable dose selected from part 1) in combination with panitumumab and AMG 479 in combination with panitumumab versus panitumumab alone |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and efficacy of AMG 102 (tolerable dose selected from part 1) in combination with panitumumab and AMG 479 in combination with panitumumab versus panitumumab alone PK exposure of AMG 102 and panitumumab when given in combination PK exposure of AMG 479 and panitumumab when given in combination PK exposure of panitumumab when given alone |
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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 |
FARMACOGENETICA: Versione:1 Data:2008/04/22 Titolo:NA Obiettivi:L`obiettivo di questo sottostudio e` capire la migliore possibilita` di cura nei soggetti con tumore del colonretto e/o la migliore possibile risposta da parte di questi per i farmaci in studio attraverso test di farmacogenetica.
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E.3 | Principal inclusion criteria |
Man or woman &#8805; 18 years of age A life expectancy estimate of &#8805; 3 months ECOG 0 or 1 Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum Subjects with wild-type KRAS tumor status confirmed by central laboratory assessment Radiographic evidence of disease progression during or following prior treatment with irinotecan and/or oxaliplatin based chemotherapy for mCRC At least 1 uni-dimensionally measurable lesion &#8805; 20 mm in one dimension per modified RECIST (CT or MRI) Adequate hematology, renal, and hepatic function Magnesium &#8805; lower limit of normal Subjects with known diabetes (Type 1 or 2) must have adequate glycemic function, as follows: - Must be controlled with a glycosylated hemoglobin (HgbA1c) of < 8.0% - Documented fasting blood sugars < 160 mg/dL |
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E.4 | Principal exclusion criteria |
Participation in a phase 3 randomized study of panitumumab in combination with chemotherapy, regardless of treatment assignment Prior treatment with anti-EGFr inhibitors (eg, panitumumab, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting &#8805; 6 months before enrollment Prior treatment with c-Met, IGF-IR, or IGF-IIR inhibitors Prior treatment with either AMG 102 or AMG 479 Use of experimental or approved systemic chemotherapy or radiotherapy &#8804; 21 days before enrollment Use of experimental or approved targeted therapies &#8804; 30 days before enrollment History of prior or concurrent central nervous system (CNS) metastases History of other primary cancer, unless: - Curatively resected non-melanomatous skin cancer - Curatively treated cervical carcinoma in situ - Other primary solid tumor treated with curative intent and no known active disease present for &#8805; 5 years before enrollment History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) &#8804; 1 year before enrollment Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as &#8805; grade 2 per CTCAE version 3.0) Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion) Serious or non-healing wound &#8804; 35 days before enrollment Major surgical procedure &#8804; 35 days before enrollment or minor surgical procedure &#8804; 14 days before enrollment. Subjects must have recovered from surgery related toxicities. Central venous catheter placement, fine needle aspiration, thoracentesis, or paracentesis is not considered a major or minor surgical procedure. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall ORR (objective response rate) |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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) | Yes |
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 | 30 |
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 | 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 study for each subject is defined as the date the subject withdraws consent from the study, completes the final long-term follow up visit, or death. This is expected to be no more than two years after teh last subject is randomized. |
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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 | |
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 |