Previously Treated, Wild-type KRAS, Metastatic Colorectal Cancer MedDRA version: 14.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 680 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 320
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 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);Main Objective: 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.;Primary end point(s): Overall Survival (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.;Timepoint(s) of evaluation of this end point: The primary analysis will occur when approximately 752 deaths are anticipated to be observed; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression free survival (PFS): time from randomization date to date of disease progression per the RECIST version 1.1 or death. Subjects alive and not meeting criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. • Overall Response Rate (ORR): The incidence of either a complete response (CR) or partial response (PR) per RECIST version 1.1 (responder). All subjects that do not meet the criteria for an objective response by the analysis cutoff date will be considered non-responders. • Duration of response: (calculated only for those subjects with an objective response) time from first objective response to disease progression per the RECIST v1.1. Subjects not meeting criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. • Time to response: time from randomization date to date of first objective response. Non-responders by the analysis data cutoff date with a best response of SD will be censored at their last assessment of SD, and subjects with all other categories of best response will be censored at the maximum observed time to a first confirmed response among all responders. • Time to treatment failure: time from randomization date to date that decision was made to end the treatment period for any reason; subjects who remain in the treatment period at the time of analysis will be censored at the date of the last on study assessment. • Patient-reported outcomes (PRO): - HRQOL: ?? EQ-5D Health Index Scale ?? EQ Visual Analog Scale - CRC Symptomatology ?? NCCN FACT Colorectal Symptom Index (FCSI) • Incidence of AEs, significant laboratory changes and immunogenicity;Timepoint(s) of evaluation of this end point: The primary analysis will occur when approximately 752 deaths are anticipated to be observed; | — |
Countries
Australia, Belgium, Bulgaria, Canada, China, Czech Republic, France, Hong Kong, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Peru, Philippines, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info – Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed