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

NCT01955629 | Terminated Phase 1 Results

• 3 other identifiers: AFLIBC065612013-000858-22U1111-1143-3015
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objectives: Study Part 1: To determine the recommended dose for the aflibercept, oxaliplatin and capecitabine (XELOX) combination to be used in the Part 2 of the study. Study Part 2: To assess the percentage of participants without progression of the disease at 6 months after the start of maintenance therapy with aflibercept single-agent, following the first-line induction therapy with XELOX and aflibercept combination in participants with previously untreated metastatic colorectal cancer. Secondary Objective: Study Part 2: Include the evaluation of progression free survival, overall survival, response to treatment, the overall safety (during induction and maintenance therapy) and the assessment of aflibercept pharmacodynamics and biomarkers parameters.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (2)

• 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.

  Cycle 1 (Up to 3 weeks)

• 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.

  6 months after the start of maintenance therapy.

Secondary Outcomes (7)

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

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

• Part 2: Progression Free Survival (PFS)

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

• Part 2: Overall Survival (OS)

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

• Part 2: Overall Rate of Resectability of Metastatic Lesions

  12 months after the last participant enrolled.

• Part 2: Number of Participants With CR or PR

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

Study Arms (1)

Aflibercept + XELOX (Oxaliplatin and Capecitabine)

EXPERIMENTAL

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

Aflibercept AVE0005 DRUG

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

Also known as: Zaltrap

Aflibercept + XELOX (Oxaliplatin and Capecitabine)

Oxaliplatin DRUG

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

Also known as: Eloxatin, SR96669

Aflibercept + XELOX (Oxaliplatin and Capecitabine)

Capecitabine DRUG

Pharmaceutical form: Tablets; Route of administration: Oral

Aflibercept + XELOX (Oxaliplatin and Capecitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically-proven adenocarcinoma of the colon or rectum.
• Metastatic disease not amenable to potentially curative treatment (i.e. unresectable).
• Measurable lesion as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• No prior systemic anti-cancer treatment for metastatic disease.
• No prior adjuvant treatment after resection of distant metastases.
• No prior treatment with angiogenesis inhibitors.

You may not qualify if:

• Age \<18 years.
• Eastern Cooperative Oncology Group Performance status \>/= 2.
• Less than 4 weeks from prior radiotherapy or prior surgery (or until the surgical wound is fully healed).
• Treatment with any other investigational product within the prior 28 days.
• Other prior neoplasm.
• History of brain metastases, active seizure disorder, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
• Any of the following within the prior 6 months: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe congestive heart failure, stroke or transient ischemic attack.
• Any of the following within the prior 3 months: moderate/severe gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
• Deep vein thrombosis within the prior 4 weeks.
• Any severe acute or chronic medical condition, which could impair the ability of the participant to participate in the study.
• Inadequate bone marrow, liver and renal function: neutrophils \< 1.5x10\^9/L, platelets \< 100x10\^9/L, hemoglobin \< 9.0 g/dL, total bilirubin \>1.5 x upper normal limit (ULN), transaminases \>3 x ULN (unless liver metastasis are present), alkaline phosphatase \>3 x ULN (unless liver metastasis are present), serum creatinine \> 1.5 x ULN.
• Participants on anticoagulant therapy with warfarin.
• Symptomatic peripheral sensory neuropathy.
• Inability to take oral medications.
• Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, malabsorption syndrome, unresolved bowel obstruction/sub-obstruction, surgery more extensive than hemicolectomy, extensive small intestine resection with chronic diarrhea.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (2)

Investigational Site Number 380-001

Genova, 16132, Italy

Location

Investigational Site Number 380-002

Milan, Italy

Location

MeSH Terms

Interventions

aflibercept; Oxaliplatin; Capecitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study enrollment was prematurely halted due to safety reasons.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2013
• First Posted: October 7, 2013
• Study Start: December 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 18, 2016
• Results First Posted: April 18, 2016

Record last verified: 2016-03

Locations

IT (2)