Estudio aleatorizado, multicéntrico, de fase 2 para comparar la eficacia de panitumumab en combinación con FOLFOX6m frente a la eficacia de bevacizumab en combinación con FOLFOX6m en pacientes con cáncer colorrectal metastásico, no resecable, con KRAS no mutado y sin tratamiento previoA Randomized, Multicenter, Phase 2 Study to Compare the Efficacy of Panitumumab inCombination With mFOLFOX6 to the Efficacy of Bevacizumab in Combination With mFOLFOX6 in Patients With Previously Untreated, KRAS Wild-Type, Unresectable, Metastatic Colorectal Cancer

Phase 1

• Conditions: Cáncer colorrectal metastásico, no resecable, con KRAS no mutado y sin tratamiento previo.Previously Untreated, KRAS Wild-Type, Unresectable, Metastatic Colorectal Cancer; MedDRA version: 9.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

• Registration Number: EUCTR2008-004281-71-ES
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01-20
• Last Update Posted: 3 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

4.1.1 Disease related
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 20mm per modified RECIST guidelines (see Appendix E) 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 paraffin-embedded tumor tissue from the primary tumor or metastasis
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix D)
4.1.2 Demographic
Man or woman 18 years of age or older at the time the informed consent is obtained
4.1.3 Laboratory
To be performed ? 7 days prior to randomization, unless otherwise specified:
Hematologic function within the following limits:
? Absolute neutrophil count (ANC) ? 1.5 x 109/L
? Platelet count ? 100 x 109/L (without platelet transfusion ? 14 days prior to
randomization)
? Hemoglobin (Hgb) ? 9.0 g/dL
Renal function within the following limits:
? Creatinine clearance (GFR) ? 50 mL/min calculated by the Cockcroft- Gault method as follows:
o Male creatinine clearance = (140 ? age in years) x (weight in Kg) / (serum creatinine in mg/dL x 72)
o Female creatinine clearance = (140 ? age) x (weight in Kg) x 0.85 / (serum creatinine in mg/dL x 72)
? Urinary protein ? 30 mg by urinalysis or ? 1+ by dipstick or urine protein creatinine (UPC) ratio ? 0.5 by urinalysis (unless excretion of < 1000 mg of protein per day as determined by 24-hour urine collection).
Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formula:
[urine protein]/[urine creatinine] - if both urine protein and creatinine are reported in mg/dL.
[(urine protein) x0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L.
Hepatic function within the following limits:
? Total bilirubin ? 1.5 x ULN
? Alkaline phosphatase ? 2.5 x ULN (if liver metastases, ? 5 x ULN)
? Aspartate aminotransferase (AST) ? 2.5 x ULN (if liver metastases, ? 5 x ULN)
? Alanine aminotransferase (ALT) ? 2.5 x ULN (if liver metastases, ? 5 x ULN)
Metabolic function within the following limits:
? Magnesium ? lower limit of normal
Coagulation function within the following limits:
? Partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT) ? 1.0 x ULN and international normalized ratio (INR) < 1.5
Negative pregnancy test ? 3 days prior to randomization (for woman of childbearing potential only)
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

4.2.1 Disease Related
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
4.2.2 Cancer Therapy
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.
Unresolved toxicities from prior anti-cancer therapy that, in the opinion of the investigator, excludes subject from participation
4.2.3 Other Medications
Any anticoagulation therapy within 7 days prior to randomization except the use of low-dose warfarin [< 2 mg daily] or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis which is allowed
Chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is also not allowed
Infection requiring a course of systemic anti-infectives that was completed ? 14 days before randomization (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection [UTI])
4.2.4 General
Significant cardiovascular risk:
? Myocardial infarction, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, percutaneous transluminal coronary angioplasty/stent, ongoing arrhythmias requiring medication or unstable angina ? 24 weeks prior to randomization
? Uncontrolled blood pressure defined as > 150 mm Hg systole or > 90 mm Hg diastole. Anti-hypertensive medications are allowed if hypertension is stably controlled at the time of randomization.
? Previous history of any CNS cerebrovascular ischemia or hemorrhage
? Pulmonary embolism, deep vein thrombosis, or other significant venous event ?8 weeks before randomization
Significant bleeding risk:
? Major surgical procedure, open biopsy, or significant traumatic injury ? 28 days before randomization or not yet recovered from prior major surgery
? Anticipation of need for major elective surgical procedures during the course of the study
? Minor surgery ?14 days prior to randomization or not yet recovered from prior minor surgery
? Core biopsy or other minor procedure ? 7 days prior to randomization (with the exception of insertion of a vascular access device)
? Pre-existing bleeding diathesis and coagulopathy
? Serious or non-healing wounds, skin ulcers, or unhealed bone fractures
? Gastroduodenal ulcer(s) determined by

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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 wildtype KRAS.;Secondary Objective: 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.;Primary end point(s): Progression-free survival (PFS): time from randomization date to date of radiologic disease progression per modified RECIST criteria or death. For subjects not meeting criteria for progression and alive at the analysis data cutoff date, PFS will be censored at their last evaluable disease assessment date.