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

NCT ID: NCT01882868

Last Updated: 2017-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-08-31

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.

Detailed Description

Screening was up to 24 days. Treatment period was continued until DP, unacceptable toxicity, or participant's refusal. Follow up period was continued until death, participant's refusal, or end of study, whichever came first.

This trial was conducted in Japan, where the International Nonproprietary Name (INN) designation for the study molecule is "aflibercept" and this term is therefore used throughout the synopsis. In the US, the US proper name is "ziv-aflibercept".

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aflibercept + FOLFIRI

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.

Group Type: EXPERIMENTAL

Aflibercept

Intervention Type: 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

Levofolinate

Intervention Type: DRUG

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

Irinotecan

Intervention Type: DRUG

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

5-FU

Intervention Type: DRUG

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

Interventions

Aflibercept

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

Intervention Type: DRUG

Levofolinate

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

Intervention Type: DRUG

Irinotecan

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

Intervention Type: DRUG

5-FU

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

Intervention Type: DRUG

Other Intervention Names

AVE0005

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 392011

Chiba, , Japan

Investigational Site Number 392018

Chūōku, , Japan

Investigational Site Number 392016

Fukuoka, , Japan

Investigational Site Number 392017

Fukuoka, , Japan

Investigational Site Number 392001

Kashiwa-Shi, , Japan

Investigational Site Number 392019

Kawasaki-Shi, , Japan

Investigational Site Number 392015

Matsuyama, , Japan

Investigational Site Number 392013

Mitaka-Shi, , Japan

Investigational Site Number 392004

Nagoya, , Japan

Investigational Site Number 392006

Osaka, , Japan

Investigational Site Number 392014

Sagamihara-Shi, , Japan

Investigational Site Number 392008

Sapporo, , Japan

Investigational Site Number 392003

Sendai, , Japan

Investigational Site Number 392009

Shimotsuke-Shi, , Japan

Investigational Site Number 392012

Shinjuku-Ku, , Japan

Investigational Site Number 392005

Suita-Shi, , Japan

Investigational Site Number 392002

Sunto-Gun, , Japan

Investigational Site Number 392010

Tsukuba, , Japan

Investigational Site Number 392007

Yufu-Shi, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 31520559 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30657223 (View on PubMed)

Other Identifiers

U1111-1120-0173

Identifier Type: OTHER

Identifier Source: secondary_id

EFC11885

Identifier Type: -

Identifier Source: org_study_id