Capecitabine Plus Aflibercept as Maintenance Therapy Following Capecitabine Plus Oxaliplatin Plus Aflibercept in Patients With Metastatic Colorectal Cancer

NCT02085005 | Withdrawn Phase 2

• 2 other identifiers: LPS13787U1111-1149-0237
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary Objective: Efficacy: To assess the progression-free survival rate at 10 months in patients on maintenance therapy with capecitabine plus aflibercept. Secondary Objectives: To evaluate:

• Efficacy: Progression Free Survival (PFS)
• Efficacy: Overall Survival (OS)
• Efficacy: Objective Response Rate (ORR) as per Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) criteria
• Health related Quality of Life (HRQL): EORTC QLQ-C30 scores and EQ5D-3L
• Safety Exploratory Objective: To collect blood and tumor samples to perform investigations for potential biomarker testing.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival rate at 10 months (PFS@10m)

  every 9 weeks, up to 28 months

Secondary Outcomes (5)

• Progression Free Survival (PFS) - Time

  every 9 weeks, up to 28 months

• Overall Survival (OS) - Time

  every 9 weeks, up to 28 months

• Assessment of Objective Response Rate (ORR)

  every 9 weeks, up to 28 months

• Total Score as a measure of Health Related Quality of Life

  every 3 weeks, up to end of treatment

• Number of participants with adverse events

  up to 30 days after last treatment

Study Arms (1)

Aflibercept

EXPERIMENTAL

Intravenous (IV) infusion on Day 1 every 3 weeks, followed by CAPOX (capecitabine by oral administration on Day 1 to Day 14 and oxaliplatin intravenous (IV) infusion on Day 1 every 3 weeks) for the induction treatment period (6 cycles) after which the patient may enter the maintenance period during which the treatment is Aflibercept + Capecitabine

Drug: Capecitabine; Drug: Aflibercept AVE0005; Drug: Oxaliplatin SR96669

Interventions

Capecitabine DRUG

Pharmaceutical form:tablet Route of administration: oral

Aflibercept

Aflibercept AVE0005 DRUG

Pharmaceutical form:concentrate for infusion Route of administration: intravenous

Aflibercept

Oxaliplatin SR96669 DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

Aflibercept

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years of both sexes
• Histologically confirmed mCRC
• Unresectable metastatic colorectal cancer. (Patient with resectable metastases (liver or lung) is not eligible.)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• A life expectancy of \>3 months
• At least one measurable lesion according to RECIST (version 1.1)
• No prior chemotherapy for advanced disease. Patients with prior (neo)adjuvant chemotherapy completed more than 6 months prior metastatic relapse are eligible (adjuvant does not include the chemotherapy after resection of distant metastases).
• Adequate hematological profile (absolute neutrophil count \>1.5 x 109/L, platelet count \>100 x 109/L, hemoglobin \>9 g/dL)
• Adequate liver function: AST, ALT \<3.0 x ULN (or \<5 xULN in the case of liver function abnormalities due to underlying liver metastases); Alkaline Phosphatase \<3 x ULN (or \<5 x ULN if due to underlying liver metastases); Total bilirubin \<1.5 x ULN
• Serum creatinine \< 1.5 x upper limit of normal (ULN). If creatinine 1.0-1.5 x ULN, creatinine clearance will be calculated according to the CKD-EPI formula and creatinine clearance \< 60 mL/min will exclude the patient
• Proteinuria \<2+ functions
• Signed patient informed consent before beginning specific protocol procedures
• Ability to comply with protocol requirements

You may not qualify if:

• Other prior neoplasm. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the patient has been disease-free for \> 5 years are allowed
• History of brain metastases (unless adequately controlled, i.e. previously irradiated, inactive brain metastases not requiring active treatment like steroids or antiepileptics), active seizure disorder, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
• Any severe acute or chronic medical condition, which could impair the ability of the patient to participate in the study or interfere with interpretation of study results. Known Acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment
• Pregnant or breast-feeding woman. Positive pregnancy test (serum or urine β-HCG) for women of reproductive potential
• Patient with reproductive potential (M/F) who do not agree to use accepted and effective method of contraception during the study treatment period and for at least 6 months after the completion of the study treatment. The definition of "effective method of contraception" will be based on the Investigator's judgment
• Patient on anticoagulant therapy with warfarin (coumarin-derivative). Anticoagulation with low molecular weight heparin (LWMH) is permitted
• Symptomatic peripheral sensory neuropathy grade ≥ 2 (NCI-CTCAE v4.03)
• 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.
• History of hypersensitivity to fluoropyrimidines or known/suspected allergy to any agent given during the study or to any excipient to study drugs
• Known dihydropyrimidine dehydrogenase deficiency
• Any contraindication to administer oxaliplatin, 5-FU, folinic acid or capecitabine as per package insert of each drug
• Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR\>1.5 without vitamine K antagonist therapy), non-healing wound
• History of hypersensitivity to Aflibercept (in case of prior administration for an indication other than cancer, i.e. ophthalmic indication)
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

MeSH Terms

Interventions

Capecitabine; aflibercept

Intervention Hierarchy (Ancestors)

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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2014
• First Posted: March 12, 2014
• Study Start: March 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: November 18, 2014

Record last verified: 2014-11