Estudio de fase 2, aleatorizado, a doble ciego y controlado con placebo para evaluar la seguridad y eficacia de FOLFIRI en combinación con AMG 479 o AMG 655 en comparación con FOLFIRI en el tratamiento de segunda línea del carcinoma colorrectal metastásico con KRAS mutado.A Phase 2, Randomized, Double-blind, Placebo-controlled Study Evaluating the Safetyand Efficacy of FOLFIRI in Combination With AMG 479 or AMG 655 Versus FOLFIRI for the Second-line Treatment of KRAS-mutant Metastatic Colorectal Carcinoma

Phase 1

• Conditions: Tratamiento de segunda línea del cáncer colorrectal metastásico con KRAS mutadoSecond-line treatment of KRAS mutant-type metastatic colorectal cancer.; MedDRA version: 9.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

• Registration Number: EUCTR2008-005301-19-ES
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-04-27
• Study Completion: 2012-06-04
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Disease Related
? Histologically confirmed adenocarcinoma of the colon or rectum in patients with
metastatic disease
? Mutant-type KRAS tumor status confirmed by central laboratory assessment of
formalin-fixed paraffin-embedded tumor tissue from the primary tumor or metastasis
? One and only one prior anti-cancer therapy regimen for metastatic disease
consisting of the combination of a fluoropyrimidine and oxaliplatin-based
chemotherapy with or without anti-VEGF therapy. Prior adjuvant or neoadjuvant
chemotherapy used prior to the onset of metastatic disease is permitted.
? Documented disease progression while receiving or ? 6 months after the last dose of prior first-line fluoropyrimidine and oxaliplatin-based chemotherapy with or without
bevacizumab for metastatic disease
? Measurable or non-measurable disease according to modified RECIST criteria.
Lesions 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.
? Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Demographic
? Men or women 18 years of age or older at the time the informed consent is obtained
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 ? 9.0 g/dL
? Renal function within the following limits:
? Creatinine clearance (GFR) ? 40 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)
? Hepatic function within the following limits
? Total bilirubin ? 1.5 mg/dL;
? 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)
? Coagulation function within the following limits:
? Partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT)
? 1.3 x ULN and international normalized ratio (INR) ? 1.5, unless subject is on
anti-coagulation therapy. Subjects on therapeutic anti-coagulation are eligible if:
o there is no bleeding and they are on a stable dose of anticoagulation therapy
(eg, warfarin with an INR of 2 to 3) for at least 14 days before randomization,
and o the patient has no active bleeding or pathological condition that carries high
risk of bleeding (eg, tumor involving major vessels or known varices)
? Subjects with diabetes (Type 1 or 2) must be adequately controlled with glycosylated hemoglobin (HgbA1c) ? 8% and fasting blood glucose level ?160 mg/dL; diabetic subjects who have recently had their glycemic control regimens adjusted and have documented fasting blood glucose concentrations ? 160 mg/dL may be considered, regardless of HgbA1c value, if per investigator discretion they are considered to have adequate glycemic function
? Negative pregnancy test ? 3 days prior to randomization (for woman of childbearing potential only)
General
? Competent to comprehend, sign, and date an institutional review board (IRB)/
Independent Ethics C

Exclusion Criteria

Disease Related
? History or known presence of 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
Cancer Therapy
? Prior irinotecan-based chemotherapy for advanced/metastatic disease
? Prior death receptor agonists (such as rhApo2/TRAIL [AMG 951]), apomab,
mapatumumab, lexatumumab, CS-1008), or other systemic IGF-1R antagonists
(such as CP-751, 951, MK0646, IMC-A12) in any setting.
? Systemic chemotherapy, hormonal therapy, immunotherapy or experimental or
approved anticancer proteins/antibodies therapy ? 21 days prior to randomization
? 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, exclude subject from participation
Other Medications
? Course of systemic anti-infective 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])
General
? Myocardial infarction, grade 2 or greater peripheral vascular disease,
cerebrovascular accident, transient ischemic attack, congestive heart failure,
percutaneous transluminal coronary angioplasty/stent, hypertension not stably
controlled pharmacologically, ongoing arrhythmias requiring medication or unstable
angina ? 24 weeks prior to randomization
? Pulmonary embolism, deep vein thrombosis, or other venous/arterial thromboembolic events ? 12 months before randomization
? Active inflammatory bowel disease or other bowel disease causing chronic diarrhea
(defined as ? CTCAE grade 2, [CTCAE version 3.0])
? Major surgical procedure ? 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 surgical procedure ? 7 days before randomization or not yet recovered from
prior minor surgery (Uncomplicated placement of vascular access device, fine needle
aspiration, thoracocentesis or paracentesis ? 3 days prior to enrollment is
acceptable)
? Any co-morbid disease or condition that in the judgment of the investigator could
increase the risk of toxicity (such as clinically significant ascites)
? Subjects known to be human immunodeficiency virus positive or known to have
chronic or active hepatitis B or C infection
? Subject is currently enrolled in, or ? 30 days has passed since subject completed
another investigational device or drug study(s), or subject is receiving other
investigational agent(s)
? Woman of child-bearing potential is pregnant or is breast feeding
? Women of childbearing potential and men who do not consent to use adequate
contraception during the course of the study and 24 weeks (for men) or 12 weeks
(for women) after the last dose of protocol-specified therapy. Adequate
contraceptive precautions include double barrier contraceptive methods
(eg, diaphragm and condom) or abstinence.
? Subjects allergic to any components that are part of the tr

Study & Design

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