E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Treated, 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 | 12.0 |
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 compare the effect of panitumumab versus cetuximab on overall survival (OS) for chemorefractory mCRC among subjects with wild-type KRAS tumors. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to compare the treatment effect of panitumumab versus cetuximab as treatment for chemorefractory mCRC among subjects with wild-type KRAS tumors: • Efficacy: progression-free survival (PFS), objective response rate (ORR), time to response, time to treatment failure, duration of response • Safety: subject incidence of AEs, significant laboratory changes, and immunogenicity • Patient Reported Outcomes (PRO) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum Metastatic disease Wild-type KRAS tumor status by protocol-specified testing (see Section 7.10) Formalin-fixed paraffin-embedded tumor tissue from either the primary tumor or a metastatic lesion must be submitted for biomarker testing (see Section 7.10) ECOG performance status of 0, 1 or 2 Measurable or non-measurable disease per RECIST version 1.1 Must have failed a prior regimen containing irinotecan for metastatic disease and a prior regimen containing oxaliplatin for metastatic disease. Oxaliplatin and irinotecan may have been administered sequentially or in combination. Failure is defined as either disease progression (clinical or radiological) or intolerance to the regimen Subjects in whom relapse is diagnosed within 6 months after completing adjuvant chemotherapy (with either an irinotecan or oxaliplatin containing regimen) will be considered as having failed a prior regimen for metastatic disease Must have previously received a thymidylate synthase inhibitor (e.g. fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) at any point for treatment of CRC Man or woman ≥ 18 years of age Hematologic function, as follows: (≤ 10 days prior to randomization) Absolute neutrophil count (ANC) ≥ 1.5 x 10 to the power of 9/L Platelet count ≥ 75 x 10 to the power of 9/L Hemoglobin ≥ 8.0 g/dL Renal function, as follows: (≤ 10 days prior to randomization) Creatinine ≤ 1.5 x ULN Hepatic function, as follows: (≤ 10 days prior to randomization) Aspartate aminotransferase (AST) ≤ 3 x ULN (if liver metastases ≤ 5 x ULN) Alanine aminotransferase (ALT) ≤ 3 x ULN (if liver metastases ≤ 5 x ULN) Total bilirubin ≤ 1.5 x ULN Metabolic function, as follows: (≤ 10 days prior to randomization) Magnesium ≥ lower limit of normal Negative pregnancy test ≤ 72 hours before randomization (for women of childbearing potential only) Competent to comprehend, sign, and date a written IEC/IRB approved informed consent form before any study-specific procedure |
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E.4 | Principal exclusion criteria |
Symptomatic brain metastases requiring treatment History of other malignancy, except: Malignancy treated with curative intent and with no known active disease present for ≥ 5 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 Known hypersensitivity to any of the protocol-specified agents or their excipients Prior anti-EGFr antibody therapy (eg, panitumumab or cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) Antitumor therapy (eg, chemotherapy, hormonal therapy, immunotherapy, antibody therapy, radiotherapy), or investigational agent or therapy ≤ 30 days before randomization. Subjects must have recovered from any acute toxicity Subject previously randomized to this study Other investigational procedures ≤ 30 days before randomization Subject currently is enrolled in or ≤ 30 days from ending other investigational device or drug study(s) Major surgery (eg, requiring general anesthesia) ≤ 28 days before randomization. Subjects must have recovered from any surgery related toxicities Clinically significant cardiovascular disease (as defined by: unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) Myocardial infarction within last 6 months before randomization History of interstitial lung disease (ILD), eg, interstitial pneumonitis, pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT or MRI History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results Subject pregnant or breast feeding, or planning to become pregnant during treatment and within 6 months after the end of treatment Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for an additional 6 months (males and females) after the end of treatment Known positive test(s) for human immunodeficiency virus infection (testing is not required in the absence of clinical suspicion) Active infection requiring systemic treatment or any uncontrolled infections ≤14 days prior to randomization Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures or is unwilling or unable to comply with study requirements |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary • OS: time from randomization date to date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact 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 | 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 | 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) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.3.1 | Comparator description |
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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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
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 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 dies. |
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |