E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Untreated, KRAS Wild-Type, Unresectable, 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 of this study is to estimate the treatment effect on progression-free survival (PFS) of panitumumab relative to bevacizumab in combination with mFOLFOX6 chemotherapy as first-line therapy for mCRC in subjects with tumors expressing wild-type KRAS. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate overall survival (OS), objective response (OR), duration of response (DOR), time to progression (TTP), time to response, resectability, safety and tolerability of panitumumab relative to bevacizumab in combination with mFOLFOX6 chemotherapy as first-line therapy for mCRC in subjects with tumors expressing wild-type KRAS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Man or woman ≥ 18 years of age at the time the informed consent is obtained ECOG performance status of 0 or 1 Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in subjects with unresectable metastatic disease At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST guidelines using conventional techniques (CT scan or MRI) or spiral CT scan. Lesion 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 Wild-type KRAS tumor status confirmed by central laboratory assessment of paraffinembedded tumor tissue from the primary tumor or metastasis Adequate hematology, renal, hepatic, and coagulation function (see Section 4.1.3) Magnesium ≥ lower limit of normal |
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E.4 | Principal exclusion criteria |
History of prior or concurrent 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 chemotherapy or other systemic anticancer therapy for the treatment of metastatic colorectal carcinoma including but not limited to bevacizumab and anti-EGFr therapy (eg, cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) Prior adjuvant chemotherapy (including oxaliplatin therapy) for the treatment of colorectal cancer ≤ 52 weeks prior to randomization with the following exceptions: Subjects may have received prior fluoropyrimidine therapy if administered solely for the purpose of radiosensitization Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities.
Significant cardiovascular risk (see Section 4.2.4) Significant bleeding risk (see Section 4.2.4) History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline CT scan Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as ≥ CTC grade 2, [CTCAE version 3.0]) Peripheral sensory neuropathy (≥ CTC grade 2 [CTCAE version 3.0] |
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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
|
approximately 36 months from the last subject 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 | 5 |
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 | 5 |