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

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• Colorectal Neoplasms 5,599

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

This study's enrollment of 4 is below the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Study arms

• Experimental
  Aflibercept + XELOX (Oxaliplatin and Capecitabine)

  Aflibercept 6 mg/kg every 3 weeks (q3w) in combination with Oxaliplatin 100 mg/m\^2 q3w and Capecitabine 850 mg/m\^2 twice daily orally (from Day 1 to Day 14 of each cycle), up to 6 cycles as induction therapy, followed by aflibercept 6 mg/kg q3w as maintenance therapy up to disease progression or unacceptable toxicity or participant's refusal of further treatment.

  Drug: Aflibercept AVE0005 · Drug: Oxaliplatin · Drug: Capecitabine

Interventions

• DrugAflibercept AVE0005

  Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

  Also known as: Zaltrap

• DrugOxaliplatin

  Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

  Also known as: Eloxatin, SR96669

• DrugCapecitabine

  Pharmaceutical form: Tablets; Route of administration: Oral

Primary outcomes

1. Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

   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)

2. Part 2: Number of Participants With Progression Free Survival (PFS) at 6 Months After the Start of Maintenance Therapy

   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.

Secondary outcomes

1. Part 1: Number of Participants With Tumor Responses (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Progressive Disease [PD])

   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).

2. Part 2: Progression Free Survival (PFS)

   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).

3. Part 2: Overall Survival (OS)

   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).

4. Part 2: Overall Rate of Resectability of Metastatic Lesions

   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.

5. Part 2: Number of Participants With CR or PR

   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).

6. Part 2: Pharmacodynamic Parameters: Modulation of Circulating Analytes

   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.

7. Part 2: Aflibercept Biomarkers Evaluation

   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.

Baseline characteristics