A Study of Aflibercept in Combination With FOLFIRI in Patients With Second-Line Metastatic Colorectal Cancer in Japan

NCT01882868 | Completed Phase 2 Results

• 2 other identifiers: EFC11885U1111-1120-0173
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 19

Brief Summary

Primary Objective: To assess efficacy aflibercept + 5-fluorouracil (5-FU)/levofolinate/irinotecan (FOLFIRI) by objective response rate (ORR). Secondary Objective: To assess the following:

• safety profile;
• progression free survival (PFS);
• overall survival (OS);
• pharmacokinetics (PK);
• immunogenicity.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Response

  Overall response in participants was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) assessed by an independent radiological review committee (IRRC) according to response evaluation criteria in solid tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions; any lymph node (target or non-target) must have reduction in the short axis to \<10 mm; PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentage of participants with overall response and the 95% confidence interval (CI) were provided. The 95% CI was calculated using normal approximation.

  Baseline and every 6 weeks until DP (maximum duration: 16.4 months)

Secondary Outcomes (26)

• Progression Free Survival (PFS)

  Baseline and every 6 weeks until DP or death, due to any cause (maximum duration: 16.4 months)

• Overall Survival (OS)

  Baseline up to death or study cut--off (maximum duration: 24.7 months)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  First dose (Day 1 of Cycle 1) of study treatment up to end of treatment visit (30 days after last dose of study treatment) (maximum duration: 77 weeks)

• Aflibercept Immunogenicity Assessment: Number of Participants With Positive Sample(s) in the Anti-drug Antibodies (ADA) Assay and in the Neutralizing Anti-drug Antibodies (NAb) Assay

  Baseline, at any time post baseline and 90 days after the last dose of aflibercept

• Maximum Observed Plasma Concentration (Cmax) for Free Aflibercept: ITT Population

  Pre-dose, 1, 4, 24, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with sparse sampling & pre-dose, 1, 2, 4, 8, 24, 48, 168, 336 hours post aflibercept infusion on Day 1 of Cycle 1 for participants with additional sampling

Study Arms (1)

Aflibercept + FOLFIRI

EXPERIMENTAL

Aflibercept 4 mg/kg intravenous (IV) infusion (1-2 hours) on Day 1 of Cycle 1 and every 2 weeks (q2w) thereafter, in combination with FOLFIRI regimen on Days 1-3 of Cycle 1 and q2w thereafter until disease progression (DP), unacceptable toxicity or participant's refusal. FOLFIRI regimen: IV infusions of levofolinate 200 mg/m\^2 (2 hours) and irinotecan 180 mg/m\^2 (90 minutes) simultaneously, followed by 5-FU 400 mg/m\^2 IV bolus injection followed by continuous IV infusion of 5-FU (46 hours) at 2400 mg/m\^2.

Drug: Aflibercept; Drug: Levofolinate; Drug: Irinotecan; Drug: 5-FU

Interventions

Aflibercept DRUG

Pharmaceutical form: Concentrated solution (100 mg/4 mL \[25 mg/mL\], 200 mg/8 mL \[25 mg/mL\]) for infusion; Route of administration: Intravenous

Also known as: AVE0005

Aflibercept + FOLFIRI

Levofolinate DRUG

Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous

Aflibercept + FOLFIRI

Irinotecan DRUG

Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous

Aflibercept + FOLFIRI

5-FU DRUG

Pharmaceutical form: Solution for infusion (marketed formulation); Route of administration: Intravenous

Aflibercept + FOLFIRI

Eligibility Criteria

• Age: 20 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 that was not amenable to potentially curative treatment.
• Participants with measurable disease.
• One prior chemotherapeutic regimen (containing oxaliplatin) for metastatic disease.
• Participants who relapsed within 6 months of completion of oxaliplatin-based adjuvant chemotherapy were also eligible.

You may not qualify if:

• Prior therapy with irinotecan.
• Less than 28 days elapsed from prior radiotherapy, prior surgery, or prior chemotherapy to the time of registration.
• Unresolved toxicity (grade \>1) from prior anticancer therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status \>1.
• Brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis.
• Other prior malignancy.
• Pregnant or breast-feeding women.
• Uncontrolled hypertension.
• Inadequate bone marrow function, liver function, or renal function.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (19)

Investigational Site Number 392011

Chiba, Japan

Location

Investigational Site Number 392018

Chūōku, Japan

Location

Investigational Site Number 392016

Fukuoka, Japan

Location

Investigational Site Number 392017

Fukuoka, Japan

Location

Investigational Site Number 392001

Kashiwa-Shi, Japan

Location

Investigational Site Number 392019

Kawasaki-Shi, Japan

Location

Investigational Site Number 392015

Matsuyama, Japan

Location

Investigational Site Number 392013

Mitaka-Shi, Japan

Location

Investigational Site Number 392004

Nagoya, Japan

Location

Investigational Site Number 392006

Osaka, Japan

Location

Investigational Site Number 392014

Sagamihara-Shi, Japan

Location

Investigational Site Number 392008

Sapporo, Japan

Location

Investigational Site Number 392003

Sendai, Japan

Location

Investigational Site Number 392009

Shimotsuke-Shi, Japan

Location

Investigational Site Number 392012

Shinjuku-Ku, Japan

Location

Investigational Site Number 392005

Suita-Shi, Japan

Location

Investigational Site Number 392002

Sunto-Gun, Japan

Location

Investigational Site Number 392010

Tsukuba, Japan

Location

Investigational Site Number 392007

Yufu-Shi, Japan

Location

Related Publications (2)

• Hamaguchi T, Denda T, Kudo T, Sugimoto N, Ura T, Yamazaki K, Fujii H, Kajiwara T, Nakajima TE, Takahashi S, Otsu S, Komatsu Y, Nagashima F, Moriwaki T, Esaki T, Sato T, Itabashi M, Oki E, Sasaki T, Chiron M, Yoshino T. Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer. Cancer Sci. 2019 Nov;110(11):3565-3572. doi: 10.1111/cas.14198. Epub 2019 Oct 21.

  PMID: 31520559 DERIVED

• Denda T, Sakai D, Hamaguchi T, Sugimoto N, Ura T, Yamazaki K, Fujii H, Kajiwara T, Nakajima TE, Takahashi S, Otsu S, Komatsu Y, Nagashima F, Moriwaki T, Esaki T, Sato T, Itabashi M, Oki E, Sasaki T, Sunaga Y, Ziti-Ljajic S, Brillac C, Yoshino T. Phase II trial of aflibercept with FOLFIRI as a second-line treatment for Japanese patients with metastatic colorectal cancer. Cancer Sci. 2019 Mar;110(3):1032-1043. doi: 10.1111/cas.13943. Epub 2019 Feb 22.

  PMID: 30657223 DERIVED

MeSH Terms

Interventions

aflibercept; Leucovorin; Irinotecan; Fluorouracil

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

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

Study Record Dates

• First Submitted: June 18, 2013
• First Posted: June 20, 2013
• Study Start: July 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: March 14, 2017
• Results First Posted: March 14, 2017

Record last verified: 2016-08

Locations

JP (19)