Study of Aflibercept as Maintenance Therapy Following Induction With Aflibercept in Combination With XELOX, as First-Line Treatment for Metastatic Colorectal Cancer Patient

DLTs were assessed using the national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 4.03. DLTs were defined as any of following AEs: grade 4 neutropenia lasting \>7 consecutive days; febrile neutropenia or neutropenic infection; grade 4 thrombocytopenia; grade 3 thrombocytopenia associated with bleeding requiring transfusion; grade 4 non-hematological treatment related event; grade 3 nausea/vomiting or diarrhea lasting \>/= 4 days despite corrective measures; grade 3 other non-hematological toxicities: anorexia, fatigue, hypertension only if G4 or not medically controlled and G3 peripheral sensory neuropathy that did not improve to G\<2 at time of retreatment; urinary protein excretion of \>3.5 gram per 24 hours that did not recover to \<2.0 gram per 24 hours within 2 weeks; symptomatic arterial thromboembolic events including cerebrovascular accidents, myocardial infarction, transient ischemic attacks, new onset or worsening of pre-existing angina.

Time frame: Cycle 1 (Up to 3 weeks)

Population: Evaluable DLT population defined as the subset of the whole part 1 participants that were exposed to at least 1 dose (even incomplete) of the study treatment and had a DLT assessment at Cycle 1.

It describes the number of participants alive without progression at 6 months after the start of Aflibercept maintenance therapy.

Time frame: 6 months after the start of maintenance therapy.

Population: Due to premature recruitment discontinuation, none of the planned efficacy analyses was performed.

Tumor assessment was performed by abdomino-pelvic computed tomography scan or magnetic resonance imaging (MRI) and chest X-ray or chest CT-scan to assess the disease status at baseline and then every 9 weeks during study treatment up to DP. Target lesions were evaluated using response evaluation criteria in solid tumors (RECIST) version 1.1, wherein CR = disappearance of all target lesions; PR = 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD; PD =20% increase in the sum of the LD of target lesions taking as reference the smallest sum in the study and SD = small changes that did not meet above criteria.

Time frame: Baseline and every 9 weeks up to DP (up to 15 months).

Population: Evaluable Population (EP) for tumor response was defined as a subset of ITT population (all participants who gave their informed consent and successfully registered into study) with measurable disease at study entry, who received at least 1 cycle of study treatment, with at least 1 post baseline tumor evaluation, except for early DP or death.

Blood and tumor samples were to be collected to evaluate proteomic biomarkers such as factors and receptors related to angiogenesis process, inflammation, and tumor progression.

Time frame: Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.

Population: Due to premature recruitment discontinuation, no samples had been collected and none of the planned biomarker analyses was performed.

Tumor assessment was performed by abdomino-pelvic computed tomography scan or MRI and chest X-ray or chest CT-scan to assess the disease status at baseline and then every 9 weeks during study treatment up to DP. Target lesions were evaluated using RECIST version 1.1, wherein CR = disappearance of all target lesions; PR = 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.

Time frame: Baseline and every 9 weeks up to end of study completion (15 months).

Population: Due to premature recruitment discontinuation, none of the planned efficacy analyses was performed.

Overall metastases resection rate was defined as the percentage of participants reaching an R0 metastases resection, defined as the complete absence of invasive carcinoma on histological examination at the time of definitive surgery.

Time frame: 12 months after the last participant enrolled.

Population: Due to premature recruitment discontinuation, none of the planned efficacy analyses was performed.

OS was defined as the time interval from the date of registration into the study to the date of death due to any cause. In the absence of confirmation of death, survival time was to be censored at the earliest between the last date the participant was known to be alive and the end of study date.

Time frame: From the date of enrollment up to the date of death (up to 15 months).

Population: Due to premature recruitment discontinuation, none of the planned efficacy analyses was performed.

Blood and tumor samples were to be collected to evaluate the pharmacodynamic parameters including the assessment of the modulation of circulating analytes such as cytokines and angiogenic factors.

Time frame: Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.

Population: Due to premature recruitment discontinuation, no samples had been collected and none of the planned efficacy/pharmacodynamic analyses was performed.

PFS was defined as the time interval from the date of registration into the study to the date of first observation of DP or death (due to any cause), whichever was first.

Time frame: From the date of enrollment up to the date of DP or death, whichever occurred first (up to 15 months).

Population: Due to premature recruitment discontinuation, none of the planned efficacy analyses was performed.